Synthesis, structural characterization, analytical profiling, and application to authentic samples of synthesized Phase I metabolites of the synthetic cannabinoid 5F-MDMB-PICA.

5F-MDMB-PICA, an indole-type synthetic cannabinoid (SC), was classified illicit globally in 2020. Although the extensive metabolism of 5F-MDMB-PICA in the human body warrants the development of robust analytical methods for metabolite detection and quantification, a current lack of reference standards for characteristic metabolites hinders such method creation. This work described the synthesis of 18 reference standards for 5F-MDMB-PICA and its possible Phase I metabolites, including three hydroxylated positional isomers R14 to R16. All the compounds were systematic characterized via nuclear magnetic resonance, Fourier transform infrared spectroscopy, and high-resolution mass spectrometry. Furthermore, two methods were developed for the simultaneous detection of all standards using liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. By comparison with authentic samples, R17 was identified as a suitable urine biomarker for 5F-MDMB-PICA uptake.

[Influencing mechanism of stand age to the accumulation of microbial residue carbon in the Pinus masso-niana plantations]. / 林龄对马尾松人工林微生物残体碳积累的影响机制.

Clarifying the accumulation pattern of soil microbial residue carbon and its contribution to soil organic carbon (SOC) across stand age is helpful to understand the mechanism underlying soil carbon cycling. In this study, we analyzed the differences of amino sugar content, physicochemical properties and microbial composition in surface soil (0-10 cm) in young (6 a), middle-aged (13 a), near-mature (29 a), mature (38 a) and over-mature (57 a) Pinus massoniana plantations of subtropical China, quantified the microbial residue carbon content and its contribution to SOC, and discussed the mechanism. The results showed that SOC, total nitrogen, amorphous iron oxide and leucine aminopeptidase contents in the middle-aged plantation were significantly lower than those in the mature plantation. Soil pH and fungal/bacteria in young plantation were significantly higher than those in other age groups. Across the stand age gradient, the ranges of microbial, fungal and bacterial residue carbon were 7.52-14.63, 4.03-8.00 and 3.48-6.63 g·kg-1, respectively. The contents of all the residue carbon were significantly higher in the mature plantation than that of the middle-aged plantation, which were positively affected by soil total nitrogen content. The contribution of microbial, fungal, and bacterial residue carbon to SOC was 59.7%-72.3%, 33.4%-45.6%, and 24.3%-30.8%, respectively. The contribution of fungal residue carbon to SOC in young plantation was significantly higher than that in other age groups, and the contribution of bacterial residue carbon to SOC in middle-aged plantation was significantly higher than that in young and near-mature plantations, both of which were affected by soil inorganic nitrogen. Fungal residue carbon content was 1.2-1.7 times as that of bacterial residue carbon content, and dominated for the accumulation of microbial residue carbon. Results of the partial least squares model showed that stand age, soil environmental factors (such as leucine aminopeptidase, amorphous iron oxide, pH, and total nitrogen), bacterial residue carbon, fungal residue carbon and the contribution of bacterial residue carbon to SOC had total effects on the contribution of fungal residue carbon to SOC (-0.37, -1.16, 0.90, 1.09, and 0.83, respectively). In conclusion, stand age promoted the accumulation of microbial residue carbon but did not increase its contribution to SOC.

Is endoscopic mucosal resection-precutting superior to conventional methods for removing sessile colorectal polyps?

We reviewed a study that reported a comparative analysis of the effects of endoscopic mucosal resection (EMR) precutting and conventional EMR for removing non-pedunculated, 10-20 mm sized colorectal polyps. We identified some statistical deficiencies in this study. In addition, we believe that the differences between the treatments failed to achieve significance, and therefore, further analysis is required.

Incidence and clinical treatment of hypertriglyceridemic acute pancreatitis: A few issues.

Hypertriglyceridemia is a well-recognized etiology of acute pancreatitis, and the incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased in frequency worldwide in response to lifestyle changes. It is crucial to identify hypertriglyceridemia as the cause of pancreatitis and initiate appropriate treatment. Insulin treatment produces effective lowering of triglycerides, but in our opinion, non-diabetic patients with HTG-AP require separate consideration to avoid hypoglycemia.

Prediction of moderately severe and severe acute pancreatitis in pregnancy: Several issues.

We reviewed a study addressing the development and validation of a prediction model for moderately severe and severe acute pancreatitis in pregnancy. We identified some statistical deficiencies in this article. In addition, we believe that the role of cholesterol as a predictor should be described in more detail.

Ecosystem service value effects of the Three Gorges Reservoir Area land use transformation under the perspective of "production-living-ecological" space.

In the context of rapid socio-economic development, eliciting "production-living-ecological" space (PLES) changes with corresponding ecosystem service benefits is critical for national land optimization and regional sustainability. Based on land use data obtained via remote sensing of 1980, 2000, 2018, and from a PLES perspective, we applied geo-information Tupu to depict land use transformations in the Three Gorges Reservoir Area (TGRA) from 1980 to 2018. The ecological/environmental effects of land use transformation were also explored based on the contribution value of ecosystem service. The results showed that both industrial production space and living space had increased from 1980 to 2018, while agricultural production space and ecological space displayed a decreasing trend. From the perspective of Tupu transformation, land use transformation pattern was relatively stable from 1980 to 2000, with the untransformed Tupu unit being dominant. However, with the complex land use transformation from 2000 to 2018, mutual transformation of agricultural production space and forest and grassland ecological space became dominant. Urbanization and industrialization were the main factors contributing to the decreased agricultural production space and ecological space. The ecosystem service value of TGRA initially decreased, then increased temporally, with greater change in the east than in the west. In the study period, ecological protection and restoration projects had positive effects on ecosystem service values, while rapid socio-economic development negatively impacted agricultural production space and ecological space. Combined with second ploughing, socio-economic development negatively impacted ecosystem ser-vice values.

Rare spontaneous extensive annular intramural esophageal dissection with endoscopic treatment: A case report.

BACKGROUND: Intramural esophageal dissection (IED) is a rare disease that should be considered in patients with chest pain, dysphagia, and hematemesis. Although it occurs most frequently in older adult women with impaired coagulation or as a sequela of endoscopy, the incidence of spontaneous IED without an obvious causative agent has risen gradually. CASE SUMMARY: This report describes a case of extensive annular IED in a 75-year-old male patient who presented with dysphagia for the past month. Esophageal barium meal radiography revealed slow passage of diluted iohexol through the esophagus after swallowing, prominent luminal dilation, obstruction of the lower segment with only a small amount of contrast medium entering the gastric cavity, and no obvious extravasation. Gastroscopy revealed smooth esophageal mucosa; several esophageal mucosal bridges and webbed mucosa were observed approximately 22 cm from the incisor. The mucosal surface was occasionally rough and uneven, and the length of the esophageal mucosal defect exceeded 10 cm. The anatomy was considered to be annular because the mucosal bridge connecting the proximal and distal tube was not attached to the surrounding myotubes. The final diagnosis was spontaneous extensive annular IED. We treated the patient successfully using endoscopic esophagotomy, which completely relieved the symptoms without complications. CONCLUSION: Spontaneous annular IED can be treated successfully by endoscopic resection of the mucosal septum between the true and false lumen.

[Root architecture and fine root characteristics of Juglans mandshurica saplings in different habitats in the secondary forest on the west slope of Zhangguangcailing, China]. / å¼ å¹¿æ‰å²­è¥¿å¡æ¬¡ç”Ÿæž—ä¸åŒç”Ÿå¢ƒèƒ¡æ¡ƒæ¥¸å¹¼æ ‘æ ¹ç³»æž„åž‹åŠç»†æ ¹ç‰¹å¾.

The whole root excavation method was used to examine root configuration of Juglans mandshurica, with the age of 5-6 years in three habitats (forest edge, gap, and canopy) in a secondary forest on the western part of Zhangguangcailing Mountains. Root structure and fine root function were measured. The root topological index, average joint length, cross-sectional area ratio before and after root branching were calculated and fine root chemical compositions were analyzed. Roots of J. mandshurica at forest edge tended to be dichotomous branch (Topological index:TI=0.68), that under the canopy were herringbone-like branch (TI=0.79), and the gap was between the two (TI=0.72). The average connection length of roots among the three habitats was not significant. The cross-sectional area ratio of roots before and after root branching in three habitats was 1.06, 1.04 and 1.07, respectively, which was not affected by root diameter, in accordance with the Leonardo da Vinci rule. For the same order fine root in different habitats, its length and specific surface area gradually increased from the edge of the forest to the canopy. The N content decreased first and then increased, while the C content and C/N increased first and then decreased. From the forest edge to the gap and to the under canopy, roots tended to move from the dichotomous branch to the herringbone-like branch by reducing the overlap between the secondary branches and roots, increasing specific root length, specific surface area and changing the contents of C and N to cope with environmental change and improve nutrient absorption efficiency.

Proteomic analysis of the cerebrospinal fluid of Parkinson's disease patients pre- and post-deep brain stimulation.

AIMS: To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action . METHODS: Cerebrospinal fluid (CSF), obtained from six Parkinson's disease (PD) patients (pre- and post-DBS) and from six normal healthy controls, was studied for differentially expressed proteins. 2-D DIGE, in combination with MALDI-TOF and TOF-TOF Mass Spectrometry (MS) or ESI-MS, was used to identify the changed proteins (3 PD patients and 3 controls). Selected proteins were further studied using western blotting (6 PD patients and 6 controls). RESULTS: Twenty-one proteins were identified after MS and protein database interrogation. Apart from apolipoprotein A-I (apoA-I), the expression levels of complement C4 (C4), IgA, tetranectin, and extracellular superoxide dismutase (EC-SOD), detected by western blotting, correlated well with the 2-D DIGE results. In the follow-up period, the expression levels of C4, apoA-I and IgA were stable whereas EC-SOD and tetranectin were significantly elevated. In addition, when DBS was ceased in one patient due to a suicide attempt, the levels of EC-SOD and tetranectin significantly decreased. CONCLUSION: Our preliminary results suggest that variations in the expression levels of EC-SOD and tetranectin in CSF is related to DBS.

Characterisation of the vitreous proteome in proliferative diabetic retinopathy.

BACKGROUND: Diabetes can lead to serious microvascular complications such as proliferative diabetic retinopathy (PDR), which results in severe vision loss. The diabetes-induced alterations in the vitreous protein composition in diabetic patients with PDR may be responsible for the presence of PDR. The vitreous humour can be utilised in a variety of studies aimed toward the discovery of new targets for the treatment or prevention of PDR and the identification of novel disease mechanisms. The aim of this study was to compare the protein profile of vitreous humour from diabetic patients with PDR with that of vitreous humour from normal human eyes donated for corneal transplant. RESULTS: Vitreous humour from type 2 diabetic patients with PDR (n = 10) and from normal human eyes donated for corneal transplant (n = 10) were studied. The comparative proteomic analysis was performed using two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). Differentially produced proteins (abundance ratio > 2 or < -2, p < 0.01) were identified by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and MALDI-TOF tandem mass spectrometry. A total of 1242 protein spots were detected on the 2-D master gel of the samples, and 57 spots that exhibited statistically significant variations were successfully identified. The spots corresponded to peptide fragments of 29 proteins, including 8 proteins that increased and 21 proteins that decreased in PDR. Excluding the serum proteins from minor vitreous haemorrhage, 19 proteins were found to be differentially produced in PDR patients compared with normal subjects; 6 of these proteins have never been reported to be differentially expressed in PDR vitreous: N(G),N(G)-dimethylarginine dimethylaminohydrolase 1 (DDAH 1), tubulin alpha-1B chain, gamma-enolase, cytosolic acyl coenzyme A thioester hydrolase, malate dehydrogenase and phosphatidylethanolamine-binding protein 1 (PEBP 1). The differential production of pigment epithelium-derived factor (PEDF) and clusterin was confirmed by Western blot analysis. CONCLUSIONS: These data provide an in-depth analysis of the human vitreous proteome and reveal protein alterations that are possibly involved in the pathogenesis of PDR. Further investigation of these special proteins may provide potential new targets for the treatment or the prevention of PDR.

Proteomic changes in articular cartilage of human endemic osteoarthritis in China.

Kashin-Beck disease (KBD) is a chronic endemic osteochondropathy with unclear pathogenesis. It is a degenerative disease similar to osteoarthritis, but with different manifestations of cartilage damage. The aim of this investigation was to show the protein changes in KBD cartilage and to identify the candidate proteins in order to understand the pathogenesis of the disease. Proteins were extracted from the media of primary cell cultures of KBD and normal chondrocytes, and separated by two-dimensional fluorescence difference gel electrophoresis (2-D DIGE). MALDI-TOF/TOF analysis revealed statistically significant differences in 27 proteins from KBD chondrocyte cultures, which consisted of 17 up-regulated and ten down-regulated proteins. The results were further validated by Western blot analysis. The proteins identified are mainly involved in cellular redox homeostasis and stress response (MnSOD, Hsp27, Peroxiredoxin-1, and Cofilin-1), glycolysis (PGK-1, PGM-1, α-enolase), and cell motility and cytoskeletal organization (Actin, Calponin-2, and Keratin). These KBD-associated proteins indicate that cytoskeletal remodeling, glycometabolism, and oxidative stress are abnormal in KBD articular cartilage.

Transport of receptors, receptor signaling complexes and ion channels via neuropeptide-secretory vesicles.

Stimulus-induced exocytosis of large dense-core vesicles (LDCVs) leads to discharge of neuropeptides and fusion of LDCV membranes with the plasma membrane. However, the contribution of LDCVs to the properties of the neuronal membrane remains largely unclear. The present study found that LDCVs were associated with multiple receptors, channels and signaling molecules, suggesting that neuronal sensitivity is modulated by an LDCV-mediated mechanism. Liquid chromatography-mass spectrometry combined with immunoblotting of subcellular fractions identified 298 proteins in LDCV membranes purified from the dorsal spinal cord, including G-protein-coupled receptors, G-proteins and other signaling molecules, ion channels and trafficking-related proteins. Morphological assays showed that δ-opioid receptor 1 (DOR1), ß2 adrenergic receptor (AR), G(αi2), voltage-gated calcium channel α2δ1 subunit and P2X purinoceptor 2 were localized in substance P (SP)-positive LDCVs in small-diameter dorsal root ganglion neurons, whereas ß1 AR, Wnt receptor frizzled 8 and dishevelled 1 were present in SP-negative LDCVs. Furthermore, DOR1/G(αi2)/G(ß1γ5)/phospholipase C ß2 complexes were associated with LDCVs. Blockade of the DOR1/G(αi2) interaction largely abolished the LDCV localization of G(αi2) and impaired stimulation-induced surface expression of G(αi2). Thus, LDCVs serve as carriers of receptors, ion channels and preassembled receptor signaling complexes, enabling a rapid, activity-dependent modulation of neuronal sensitivity.

[Shotgun proteomic analysis of intervertebral disc tissues from fetal and adult subjects].

OBJECTIVE: To acquire information on the IVD (intervertebral disc) proteome and analyze the differences of identified proteins during IVD development and maturation by a shotgun proteomics approach so as to identify the global protein expression patterns of IVD tissues from fetus and adults. METHODS: A 24-week fetus, a 25- and a 30-year-old adult IVD samples were collected and SDS-PAGE, RP-HPLC MS/MS shotgun analyses were performed. Bioinformational analysis with International Protein Index (IPI) database and functional classification with Gene Ontology Annotation (GOA) database were used to evaluate the results. RESULTS: A total of 524 proteins were identified in fetal IVD sample while 181 and 172 proteins were observed in 25 and 30-year-old samples respectively. Forty-eight proteins existed in three samples while 84 proteins in the 25-years-old and 30-years-old samples but not in fetus. Only 174 high-quality proteins existed in fetal sample while 20 high-quality proteins in 25-year-old and 30-year-old samples. The physico-chemical characteristics of identified proteins displayed similar trends in three samples. CONCLUSIONS: This study represents the first presentation of a global proteomic map of fetal and adult IVD samples using shotgun technology. Substantial differences exist in number and variety of proteins between development and mature IVD. This contributes to our overall knowledge in of biochemical components, metabolic regulation and biological mechanics in IVD.

Proteomics approach to study the mechanism of action of grape seed proanthocyanidin extracts on arterial remodeling in diabetic rats.

Arterial remodeling is the change in structural properties of vessel in diabetes mellitus and contributes to the development of vascular complications. To prevent this development and to improve diabetic vascular complications, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating arteriosclerosis, while little is known about the functional protein changes. We used streptozocin to induce diabetic rats. GSPE (250 mg/kg body weight/day) were administrated to diabetic rats for 24 weeks. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate aortic protein profiles among the control, untreated and GSPE- treated diabetic rats. The expression of 23 proteins was found either up-regulated or down-regulated in the aorta of untreated diabetic rats. Only the expression of 15 proteins was found either down-regulated or up-regulated in the aorta of GSPE- treated diabetic rats. Our findings might help to better understand the mechanism of diabetic macrovascular complications and provide novel targets for evaluating the effects of GSPE therapy.