Development and evaluation of a deep learning-based model for simultaneous detection and localization of rib and clavicle fractures in trauma patients' chest radiographs.

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm. Materials and methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps. Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures. Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

Deep-learning reconstruction of complex dynamical networks from incomplete data.

Reconstructing complex networks and predicting the dynamics are particularly challenging in real-world applications because the available information and data are incomplete. We develop a unified collaborative deep-learning framework consisting of three modules: network inference, state estimation, and dynamical learning. The complete network structure is first inferred and the states of the unobserved nodes are estimated, based on which the dynamical learning module is activated to determine the dynamical evolution rules. An alternating parameter updating strategy is deployed to improve the inference and prediction accuracy. Our framework outperforms baseline methods for synthetic and empirical networks hosting a variety of dynamical processes. A reciprocity emerges between network inference and dynamical prediction: better inference of network structure improves the accuracy of dynamical prediction, and vice versa. We demonstrate the superior performance of our framework on an influenza dataset consisting of 37 US States and a PM2.5 dataset covering 184 cities in China.

CD177 drives the transendothelial migration of Treg cells enriched in human colorectal cancer.

Objectives: Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor-infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor-infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness. Methods: Single-cell RNA sequencing (scRNA-seq) data and survival data were obtained from public databases. Twenty-one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177+ Treg cells was substantiated using in vitro experiments. Results: ScRNA-seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177+ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177- Treg cells. We further discovered that both intratumoral CD177+ Treg cells and CD177-overexpressing induced Treg (iTreg) cells had lower levels of PD-1 than their CD177- counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells in vitro. Conclusions: These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR-T) cell therapy.

Miniaturized Implantable Fluorescence Probes Integrated with Metal-Organic Frameworks for Deep Brain Dopamine Sensing.

Continuously monitoring neurotransmitter dynamics can offer profound insights into neural mechanisms and the etiology of neurological diseases. Here, we present a miniaturized implantable fluorescence probe integrated with metal-organic frameworks (MOFs) for deep brain dopamine sensing. The probe is assembled from physically thinned light-emitting diodes (LEDs) and phototransistors, along with functional surface coatings, resulting in a total thickness of 120 µm. A fluorescent MOF that specifically binds dopamine is introduced, enabling a highly sensitive dopamine measurement with a detection limit of 79.9 nM. A compact wireless circuit weighing only 0.85 g is also developed and interfaced with the probe, which was later applied to continuously monitor real-time dopamine levels during deep brain stimulation in rats, providing critical information on neurotransmitter dynamics. Cytotoxicity tests and immunofluorescence analysis further suggest a favorable biocompatibility of the probe for implantable applications. This work presents fundamental principles and techniques for integrating fluorescent MOFs and flexible electronics for brain-computer interfaces and may provide more customized platforms for applications in neuroscience, disease tracing, and smart diagnostics.

Enhancing regional control in p16-negative oropharyngeal cancer: A propensity score-matched analysis of upfront neck dissection and definitive chemoradiotherapy.

BACKGROUND: The presence of p16 and neck disease are important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospectively study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs. 61.0%, p=0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (HR=0.110; 95% CI, 0.014-0.879; p=0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.

Effect of phosphoric acid additive on the electrolyte of all-vanadium flow batteries.

A phosphoric acid additive with an optimal concentration of 0.1 M can vastly promote the diffusion kinetics of the redox reaction between V(IV) and V(V) without a significant decline in energy efficiency for 300 cycles, and maintain the high-temperature stability (55 °C) of an electrolyte at a high state of charge (SOC) of 70% over the course of 30 days.

Sirt6 promotes DNA damage repair in osteoarthritis chondrocytes by activating the Keap1/Nrf2/HO-1 signaling pathway.

The aim of this study was to explore the effect and mechanism of Sirt6 on DNA damage repair in OA chondrocytes. Cartilage tissues were collected from OA patients with knee arthroplasty and traumatic amputation patients without OA. Besides, 7-week-old male C57BL/6 mice were randomly divided into Control and OA groups; CHON-001 cells of corresponding groups were treated with 10 ng/ml interleukin (IL)-1ß, respectively. Subsequently, Sirt6 or siNrf2 was over-expressed in CHON-001 cells to observe the effect of Sirt6 on DNA damage and senescence of chondrocytes by IL-1ß through the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. The expression level of Sirt6 in human and mouse OA cartilage tissues was significantly decreased. However, 24 h of treatment with IL-1ß significantly decreased the expression of Sirt6 in chondrocytes, induced DNA damage, and promoted cellular senescence. In addition, over-expression of Sirt6 promoted DNA damage repair and inhibited cellular senescence in IL-1ß-induced chondrocytes. Moreover, the overexpression of Sirt6 activated the Keap1/Nrf2/HO-1 signaling pathway in chondrocytes, while knockdown of Nrf2 expression inhibited the DNA damage repair and anti-senescence effects of Sirt6 on IL-1ß-treated chondrocytes. Sirt6 may reduce DNA damage and cellular senescence in OA chondrocytes induced by IL-1ß through activating the Keap1/Nrf2/HO-1 signaling pathway.

Higher early pregnancy plasma myo-inositol associates with increased postprandial glycaemia later in pregnancy: Secondary analyses of the NiPPeR randomized controlled trial.

AIM: Myo-inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at-risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo-inositol-containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. METHODS: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo-inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. RESULTS: Higher 7-week myo-inositol, but not 28-week myo-inositol, associated with higher 1 h PG [ßadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge µmol/L, p = .022] and 2 h PG [0.08 (0.03, 0.12), p = .001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7-week myo-inositol increase of 23.4 µmol/L with myo-inositol supplementation. Higher 7-week myo-inositol associated with a lower 28-week Stumvoll index (first phase), an approximation of insulin secretion [-0.08 (-0.15, -0.01), p = .020] but not with 28-week Matsuda insulin sensitivity index. However, the clinical significance of a 7-week myo-inositol-related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C-peptide levels. In-silico modelling found higher 28-week myo-inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7-week myo-inositol effects. CONCLUSION: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo-inositol may slightly exacerbate later pregnancy post-challenge glycaemia, indicating that the optimal timing for starting prenatal myo-inositol supplementation needs further investigation.

A phase 4 multicentre, 2×2 factorial randomised, double-blind, placebo-controlled trial to investigate the efficacy and safety of tobramycin inhalation solution for Pseudomonas aeruginosa eradication in bronchiectasis: ERASE.

Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2 weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750 mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300 mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300 mg tobramycin and 750 mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36 weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.

MBene with Redox-Active Terminal Groups for an Energy-Dense Cascade Aqueous Battery.

Two-dimensional (2D) transition metal borides (MBenes), new members of the 2D materials family, hold great promise for use in the electrocatalytic and energy storage fields because of their high specific area, high chemical activity, and fast charge carrier mobility. Although various types of MBenes are reported, layered MBenes featuring redox-active terminal groups for high energy output are not yet produced. A facile and energy-efficient method for synthesizing MBenes equipped with redox-active terminal groups for cascade Zn||I2 batteries is presented. Layered MBenes have ordered metal vacancies and ─Br terminal groups, enabling the sequential reactions of I-/I0 and Br-/Br0. The I2-hosting MBene-Br cathode results in a specific energy as high as 485.8 Wh kg-1 at 899.7 W kg-1 and a specific power as high as 6007.7 W kg-1 at 180.2 Wh kg-1, far exceeding the best records for Zn||I2 batteries. The results of this study demonstrate that the challenges of MBene synthesis can be overcome and reveal an efficient path for producing high-performance redox-active electrode materials for energy-dense cascade aqueous batteries.

One-pot tandem reduction and site-selective halogenation of nitroarenes.

Halogenated aryl amines are a widely used chemical feedstock in the pharmaceutical and agrochemical industries. Achieving a single regioselective product from the para-selective halogenation of the aryl ring is significantly challenging because of the presence of several C-H bonds with similar reactivities. In this study, single para-halogenated aniline derivatives were prepared by the cascade para-selective halogenation (Cl, Br) and reduction of nitrobenzene derivatives using a mixture of SnCl2/SnCl4 salts. The mechanistic study confirmed that the noncovalent interactions between the chalcogen bond and Sn salt were pivotal for achieving regioselectivity. This synthetic method was applied for the development of potent and highly selective positron emission tomography molecular probes for serotonin transporters.

Ion Sieve Interface Assisted Zinc Anode with High Zinc Utilization and Ultralong Cycle Life for 61 Wh/kg Mild Aqueous Pouch Battery.

The cycling stability of a thin zinc anode under high zinc utilization has a critical impact on the overall energy density and practical lifetime of zinc ion batteries. In this study, an ion sieve protection layer (ZnSnF@Zn) was constructed in situ on the surface of a zinc anode by chemical replacement. The ion sieve facilitated the transport and desolvation of zinc ions at the anode/electrolyte interface, reduced the zinc deposition overpotential, and inhibited side reactions. Under a 50% zinc utilization, the symmetrical battery with this protection layer maintained stable cycling for 250 h at 30 mA cm-2. Matched with high-load self-supported vanadium-based cathodes (18-20 mg cm-2), the coin battery with 50% zinc utilization possessed an energy density retention of 94.3% after 1000 cycles at 20 mA cm-2. Furthermore, the assembled pouch battery delivered a whole energy density of 61.3 Wh kg-1, surpassing the highest mass energy density among reported mild zinc batteries, and retained 76.7% of the energy density and 85.3% (0.53 Ah) of the capacity after 300 cycles.

Associations of cord plasma per- and polyfluoroakyl substances (PFAS) with neonatal and child body composition and adiposity: The GUSTO study.

BACKGROUND: The influence of prenatal exposure to per- and poly- fluoroalkyl substances (PFAS) on birth size and offspring adiposity is unclear, especially for the newer, shorter-chained replacement PFAS. METHODS: In the GUSTO multi-ethnic Singaporean mother-offspring cohort, 12 PFAS were measured in 783 cord plasma samples using ultra-performance-liquid chromatography-tandem-mass-spectrometer (UPLC-MS/MS). Outcomes included offspring anthropometry, other indicators of body composition/metabolic health, and MRI-derived abdominal adiposity (subset) at birth and 6 years of age. PFAS were modeled individually, in categories of long-chain and short-chain PFAS, and as scores of three principal components (PC) derived using PC analysis (PC1, PC2, and PC3 reflect predominant exposure patterns to "very-long-PFAS", "long-PFAS", and "short-PFAS", respectively). Associations with outcomes were assessed using multivariable linear regressions, adjusted for important covariates such as maternal sociodemographic and lifestyle factors. RESULTS: Overall, cord PFAS levels showed either no or positive associations (mostly for long-chain PFAS) with birth weight, length and head circumference. In general, PFAS were associated with higher neonatal abdominal adiposity, driven by shorter-chain PFAS. Perfluoroheptanoic acid (PFHpA) was associated with higher volumes of superficial subcutaneous adipose tissue (sSAT) (3.75 [1.13, 6.37] mL per SD increase in PFAS) and internal adipose tissue (IAT) (1.39 [0.41, 2.38] mL). Higher levels of perfluorobutanesulfonic acid (PFBS), short-chain PFAS, and PC3 were associated with higher IAT volume (ß range 1.22-1.41 mL/SD, all P < 0.02), especially in girls. Higher PC3 score was additionally associated with higher sSAT (3.12 [0.45, 5.80] mL) volume. At age 6 years, most observed associations did not persist. No consistent associations were observed between PFAS and whole-body adiposity measures. CONCLUSIONS: Fetal exposure to emerging short-chain PFAS was associated with higher abdominal adiposity at birth but not at age 6 years. Further research is needed to replicate the findings and to determine if these effects may reappear beyond early childhood. Population exposure to newer PFAS and consequent health impact must be monitored.

The effect of transarterial embolization and nephrectomy on acute kidney injury in patients with blunt renal trauma: An American College of Surgeons - Trauma Quality Improvement Program analysis.

INTRODUCTION: Transarterial embolization (TAE) or nephrectomy for patients with blunt renal trauma might result in acute kidney injury (AKI). Thus, we analyzed the American College of Surgeons - Trauma Quality Improvement Program (TQIP) to validate this. We hypothesized that nephrectomy, and not TAE, would be a risk factor for AKI in patients with blunt renal trauma. MATERIAL AND METHODS: Adult patients with blunt injuries from the TQIP between 2017 and 2019 were eligible for inclusion. The patients were divided into three treatment groups: conservative treatment, TAE, and nephrectomy. Multivariable logistic regression was used to clarify the AKI predictors. RESULTS: The study included 12,843 patients, wherein 12,373 (96.3 %), 229 (1.8 %), and 241 (1.9 %) patients were in the conservative, TAE, and nephrectomy groups, respectively. A total of 269 (2.2 %), 20 (8.7 %), and 29 (12.0 %) patients had AKI in the three groups, respectively. Both TAE (odds ratio [OR], 2.367; 95 % confidence interval [CI], 1.372-3.900; p = 0.001) and Nephrectomy (OR, 2.745; 95 % CI, 1.629-4.528; p < 0.001) were a statistically significant predictor for AKI in the multivariable logistic regression. CONCLUSIONS: TAE and nephrectomy were statistically associated with AKI in patients with blunt renal trauma. This result differs from our previous research findings that nephrectomy, but not TAE, was a risk factor for AKI in patients with blunt renal trauma. Further prospective and well-designed research may be needed.

Hydrothermal carbonisation of polyvinyl chloride in ethanol-water/water system for solid fuels: Dechlorination, characteristics analysis of hydrochar, and reaction path.

Polyvinyl chloride (PVC) waste plastic is a typical solid waste. In this paper, the dechlorination and carbonization behavior of PVC in ethanol-water/water system under different process parameters (temperature, residence time, solid-liquid ratio) was studied, and hydrothermal carbon was characterized by SEM, elemental analysis, TG-DTG, XPS, Py-GC/MS. The results show that temperature is the key to the hydrothermal dechlorination of PVC, and the dechlorination efficiency of PVC is the highest by parameter optimization (220°C-90 min-10% S/D-80% E/D), which can reach 96.33 %. With the removal of Cl, the surface of the PVC matrix changed from full and smooth flocculent to honeycomb with uniform pore size distribution. Thermogravimetric analysis shows that the combustion of hydrochar can be divided into three stages: HCl precipitation and volatile combustion, semi-coke and coke combustion, and fixed carbon combustion. The combustion parameters and kinetic parameters of hydrochar were measured, and it was found that the hydrothermal carbonization of PVC at higher temperatures and ethanol-water ratio could improve the combustion performance of hydrochar. The highest calorific value can reach 36.68 MJ/mol. Py-GC/MS analyzed the distribution of the pyrolysis products, and alkylbenzene and aliphatic were the main products of pyrolysis. The structural analysis of hydrochar showed that C-C and CC accounted for the largest proportion, accompanied by a small amount of C-O and CO and trace C-Cl. The possible reaction mechanism of the hydrothermal carbonization of PVC was analyzed based on the distribution of functional groups and compound composition. This work provides an effective and sustainable method for the recycling of refractory chlorinated plastics.

Research progress in improving sludge dewaterability: sludge characteristics, chemical conditioning and influencing factors.

Sludge from wastewater treatment processes with high water content and large volume has become an inevitable issue in environmental management. Due to the challenging dewatering properties of sludge, current mechanical dewatering methods are no longer sufficient to meet the escalating water content standards of sludge. This paper summarizes the characteristics of various sludge and raises reasons for the their dewaterability differences. Affected by extracellular polymeric substances, biological sludge is hydrophilic and negatively charged, which limits the dewatering degree. The rheological properties, flocs, ionic composition, and solid phase concentration of the sludge also influence the dewatering to some extent. For these factors, the chemical conditioning measures with simple operation and excellent effect improve its dewaterability, which mainly include flocculation/coagulation, acid/alkali treatment, advanced oxidation, surfactant treatment and combined treatment. There is a growing necessity to explore the development of new chemical conditioning agents, even though traditional agents continue to remain widely used. However, the development of these new agents should prioritize finding a balance between various factors such as efficiency, effectiveness, ease of operation, environmental safety, and cost-effectiveness. Electrochemical dewatering enhances solid-liquid separation, and its coupling with chemical conditioning is also an excellent means to further reduce water content. In addition, the improvement of press filter is an effective way, which is influenced by pressure, processing time, sludge cake thickness and pore structure, filter media etc. In general, it is essential to develop new conditioning agents and enhance mechanical filtration press technology based on a thorough understanding of various sludge properties. Concurrently, an in-depth study of the principles of mechanical pressure filtration will contribute to establishing a theoretical foundation for effective deep sludge dewatering and propel further advancements in this field.

Feasibility of non-operative management for patients sustained blunt splenic traumas with concomitant aortic injuries.

PURPOSE: This study aimed to elucidate the treatment approach for blunt splenic injuries concurrently involving the aorta. We hypothesized that non-operative management failure rates would be higher in such cases, necessitating increased hemorrhage control surgeries. METHODS: Data from the Trauma Quality Improvement Program spanning 2017 to 2019 were utilized. All patients with blunt splenic trauma were considered for inclusion. We conducted comparisons between blunt splenic trauma patients with and without thoracic or abdominal aortic injuries to identify any potential disparities in treatment. RESULTS: Among the 32,051 patients with blunt splenic injuries during the study period, 752 (2.3%) sustained concurrent aortic injuries. Following 2:1 propensity score matching, it was determined that the presence of aortic injuries did not significantly affect the utilization of splenic transarterial angioembolization (TAE) (7.2% vs. 8.7%, p = 0.243) or the necessity for splenectomy or splenorrhaphy (15.3% vs. 15.7%, p = 0.853). Moreover, aortic injuries were not a significant factor contributing to TAE failure, regardless of the location or severity of the injury. Patients with simultaneous splenic and aortic injuries required more red blood cell transfusion within first 4 hours (0 ml [0, 900] vs. 0 ml [0, 650], p = 0.001) and exhibited a higher mortality rate (10.6% vs. 7.9%, p = 0.038). CONCLUSION: This study demonstrated that patients with concurrent aortic and splenic injuries presented with more severe conditions, higher mortality rates, and extended hospital stays. The presence of aortic injuries did not substantially influence the utilization of TAE or the necessity for splenectomy or splenorrhaphy. Patients of this type can be managed in accordance with current treatment guidelines. Nonetheless, given their less favorable prognosis, they necessitate prompt and proactive intervention.

Differential roles of serotonin receptor subtypes in regulation of neurotrophin receptor expression and intestinal hypernociception.

OBJECTIVES: Aberrant serotonin (5-hydroxytryptamine, 5-HT) metabolism and neurite outgrowth were associated with abdominal pain in irritable bowel syndrome (IBS). We previously demonstrated that 5-HT receptor subtype 7 (5-HT7) was involved in visceral hypersensitivity of IBS-like mouse models. The aim was to compare the analgesic effects of a novel 5-HT7 antagonist to reference standards in mouse models and investigate the mechanisms of 5-HT7-dependent neuroplasticity. METHODS: Two mouse models, including Giardia post-infection combined with water avoidance stress (GW) and post-resolution of trinitrobenzene sulfonic acid-induced colitis (PT) were used. Mice were orally administered CYY1005 (CYY, a novel 5-HT7 antagonist), alosetron (ALN, a 5-HT3 antagonist), and loperamide (LPM, an opioid receptor agonist) prior to measurement of visceromotor responses (VMR). Levels of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin receptors (NTRs) were assessed. RESULTS: Peroral CYY was more potent than ALN or LPM in reducing VMR values in GW and PT mice. Increased mucosal 5-HT7-expressing nerve fibers were associated with elevated Gap43 levels in the mouse colon. We observed higher colonic Ntrk2 and Ngfr expression in GW mice, and increased Bdnf expression in PT mice compared with control mice. Human SH-SY5Y cells stimulated with mouse colonic supernatant or exogenous serotonin exhibited longer nerve fibers, which CYY dose-dependently inhibited. Serotonin increased Ntrk1 and Ngfr expression via 5-HT7 but not 5-HT3 or 5-HT4, while Ntrk2 upregulation was dependent on all three 5-HT receptor subtypes. CONCLUSIONS: Stronger analgesic effects by peroral CYY were observed compared with reference standards in two IBS-like mouse models. The 5-HT7-dependent NTR upregulation and neurite elongation may be involved in intestinal hypernociception.

Syntheses, Characterization, Crystal Structures and Xanthine Oxidase Inhibitory Activity of Hydrazones.

Four new fluoro-containing hydrazones were synthesized from 4-fluorobenzaldehyde with chloro- and nitro-substituted benzohydrazides. They are 3-chloro-N'-(4-fluorobenzylidene)benzohydrazide (1), 2-chloro-N'-(4-fluorobenzylidene)benzohydrazide (2), N'-(4-fluorobenzylidene)-4-nitrobenzohydrazide (3), and N'-(4-fluorobenzylidene)-3-nitrobenzohydrazide (4). The compounds have been characterized by IR and 1H NMR spectra, as well as X-ray single crystal determination. Xanthine oxidase (XO) inhibitory activity indicated that the nitro substituted compounds 3 and 4 have effective activity. Docking simulation was performed to insert the compounds into the crystal structure of xanthine oxidase at the active site to investigate the probable binding modes.

Copper(II) and Nickel(II) Complexes Derived from Isostructural Bromo- and Fluoro-Containing Bis-Schiff Bases: Syntheses, Crystal Structures and Antimicrobial Activity.

A mononuclear copper(II) complex [CuLa] (1), and three mononuclear nickel(II) complexes [NiLa] (2), [NiLa]·CH3OH (2·CH3OH) and [NiLb] (3), where La and Lb are the dianionic form of N,N'-bis(4-bromosalicylidene)-1,2-cyclohexanediamine (H2La) and N,N'-bis(4-fluorosalicylidene)-1,2-cyclohexanediamine (H2Lb), respectively, were prepared and structurally characterized by spectroscopy method and elemental analyses. The detailed structures were determined by X-ray single crystal diffraction. All the copper and nickel complexes are mononuclear compounds. The metal ions in the complexes are in square planar coordination, with the two phenolate oxygens and two imine nitrogens of the Schiff base ligands. The biological effect of the four complexes were assayed on the bacteria strains Staphylococcus aureus, Escherichia coli and Candida albicans.