Access to 2-Alkyltropones via Organic Base-Catalyzed Tandem Deamination and Aldol Condensation of Tropinone-Derived Quaternary Ammonium Salts.

The tropone skeleton exists in a number of natural products and bioactive substances, and currently, the applications of substituted tropones are significantly limited by their preparative methods. Herein, we report a very convenient method to access 2-alkyltropones via organic base-catalyzed tandem reaction of tropinone-derived quaternary ammonium salts. Tropinone methiodide reacted with a wide variety of aromatic and aliphatic aldehydes in the presence of 1,4-diazabicyclo[2.2.2]octane to afford structurally diverse 2-alkyltropones in moderate to excellent yields with extremely high site selectivity. The reaction employs readily available feedstocks and reagents, is free of transition metals and compatible with water and air, tolerates a variety of functional groups, and can be easily scaled up. Moreover, the products are amenable to various synthetic transformations. Preliminary mechanistic studies revealed that the reaction proceeded via tandem deamination, aldol condensation, and isomerization.

Sound transmission across locally resonant honeycomb sandwich meta-structures with large spatial periodicity.

Honeycomb sandwich structures have been widely used in the field of engineering owing to their outstanding mechanical properties. However, for a honeycomb sandwich structure with large spatial periodicity, there is a low-frequency sound insulation valley. Here, the sound transmission across locally resonant honeycomb sandwich meta-structures was investigated to overcome this sound-insulation valley. An analytical model was developed based on the space-harmonic approach and the low-frequency sound insulation valley was determined analytically and numerically. The results indicate that the resonator distributed at the center of the face panel has a significant impact on the sound transmission performance of the honeycomb sandwich structure, whereas the resonator distributed on the wall of the honeycomb core does not contribute to overcoming this sound-insulation valley. Based on the research results, a design strategy for overcoming this sound-insulation valley was determined by tuning the damping parameter and constructing graded resonators. Moreover, sound transmission under the excitation of oblique incidence sound waves was also investigated. Compared with the method of filling porous materials, the proposed design method is more effective, and more importantly, the mass of the resonator is only 1.23% of that of the porous materials.

Reduced intracellular chloride concentration impairs angiogenesis by inhibiting oxidative stress-mediated VEGFR2 activation.

Chloride (Cl-) homeostasis is of great significance in cardiovascular system. Serum Cl- level is inversely associated with the mortality of patients with heart failure. Considering the importance of angiogenesis in the progress of heart failure, this study aims to investigate whether and how reduced intracellular Cl- concentration ([Cl-]i) affects angiogenesis. Human umbilical endothelial cells (HUVECs) were treated with normal Cl- medium or low Cl- medium. We showed that reduction of [Cl-]i (from 33.2 to 16.18 mM) inhibited HUVEC proliferation, migration, cytoskeleton reorganization, tube formation, and subsequently suppressed angiogenesis under basal condition, and VEGF stimulation or hypoxia treatment. Moreover, VEGF-induced NADPH-mediated reactive oxygen species (ROS) generation and VEGFR2 axis activation were markedly attenuated in low Cl- medium. We revealed that lowering [Cl-]i inhibited the expression of the membrane-bound catalytic subunits of NADPH, i.e., p22phox and Nox2, and blunted the translocation of cytosolic regulatory subunits p47phox and p67phox, thereby restricting NADPH oxidase complex formation and activation. Furthermore, reduced [Cl-]i enhanced ROS-associated protein tyrosine phosphatase 1B (PTP1B) activity and increased the interaction of VEGFR2 and PTP1B. Pharmacological inhibition of PTP1B reversed the effect of lowering [Cl-]i on VEGFR2 phosphorylation and angiogenesis. In mouse hind limb ischemia model, blockade of Cl- efflux using Cl- channel inhibitors DIDS or DCPIB (10 mg/kg, i.m., every other day for 2 weeks) significantly enhanced blood flow recovery and new capillaries formation. In conclusion, decrease of [Cl-]i suppresses angiogenesis via inhibiting oxidase stress-mediated VEGFR2 signaling activation by preventing NADPH oxidase complex formation and promoting VEGFR2/PTP1B association, suggesting that modulation of [Cl-]i may be a novel therapeutic avenue for the treatment of angiogenic dysfunction-associated diseases.

Orobanone analogues from acid-promoted aromatization rearrangement of curcumol inhibit hypoxia-inducible factor-1 (HIF-1) in cell-based reporter assays.

In this paper, the mechanism of orobanone analogues formation via aromatization rearrangement of curcumol was minutely explored. Aromatization of curcumol with acetone under acidic condition was selected as the model reaction. The formation of a stable aromatic system was the driving force for this reaction. Based on the model reaction, other four new orobanone analogues were prepared through curcumol reacting with different carbonyl compounds. The results showed that the stability of carbocation, which was generated from the carbonyl compounds, and the steric hindrance were main factors affecting the aromatization. We also synthesized the analogue of aromaticane B using compound 2. In vitro anti-proliferative activity of some derivatives were tested by MTT assay. Two derivatives showed weak anti-tumor effect on two cancer cell lines (HepG2 and MCF7) under normoxia. Four orobanone analogue 2, 5, 6 and 9 significantly inhibited hypoxia-induced HIF-1 luciferase reporter activity in HeLa cells with the IC50 values of 13.6, 6.6, 2.4 and 18.2 µM, respectively.

Stability and stabilization of (-)-gallocatechin gallate under various experimental conditions and analyses of its epimerization, auto-oxidation, and degradation by LC-MS.

BACKGROUND: (-)-Gallocatechin gallate (GCG) shows multi-bioactivities. Its stability, however, has not been investigated systematically yet. Therefore, the objective of this study was to characterize the stability of GCG and to find ways to stabilize it in biological assays. Furthermore, the epimerization of the compound, its auto-oxidation and degradation were also analyzed by liquid chromatography mass spectrometry (LC-MS). RESULTS: The stability of GCG was concentration-dependent and was sensitive to pH, temperature, bivalent cations, and dissolved oxygen level. The results also showed that GCG was not stable in common buffers (50 mmol L-1 , pH 7.4, 37 °C) or in cell culture medium DMEM/F12 under physiological conditions (pH 7.4, 37 °C). Our experiments indicated that nitrogen-saturation and the addition of ascorbic acid (VC) could stabilize GCG in biological assays. In addition, LC-MS determination indicated that GCG was able to be epimerized to its epimer (-)-epigallocatechin gallate (EGCG). Meanwhile it was also able to be auto-oxidized to theasinensin and compound P2 and degraded to gallocatechin and gallic acid in pure water at 100 °C. CONCLUSION: The stability of GCG should be seriously considered in research on the bioactivity of it to avoid possible artifacts. Nitrogen-saturation and use of VC are good ways to make GCG stable in biological assays. © 2019 Society of Chemical Industry.

[Coagulation function and hemorrhagic diseases in preterm infants with different gestational ages].

OBJECTIVE: To study the correlation between coagulation function and gestational age in preterm infants and the possible value of coagulation function measurement in predicting hemorrhagic diseases. METHODS: The clinical data of preterm infants who were hospitalized between September 2016 and August 2017 were collected. The coagulation indicators were measured within 2 hours after birth. According to the gestational age, the preterm infants were divided into late preterm infant group (n=322), early preterm infant group (n=241) and extremely/very early preterm infant group (n=128). Coagulation function was compared among the three groups, as well as between the preterm infants with and without hemorrhagic diseases within 3 days after birth. RESULTS: There were significant differences in thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) and D-dimer (DD) among the three groups (P<0.05). APTT, PT, FDP and DD were negatively correlated with gestational age, while TT was positively correlated with gestational age (P<0.05). The preterm infants with hemorrhagic diseases had a longer APTT and a higher level of DD (P<0.05). CONCLUSIONS: Coagulation function gradually becomes mature in preterm infants with the increase in gestational age. Abnormal APTT and DD indicate that preterm infants may have a higher risk of hemorrhagic diseases.

Exposure to Radon and Kidney Cancer: A Systematic Review and Meta-analysis of Observational Epidemiological Studies.

OBJECTIVE: To evaluate the possible association between radon exposure and kidney cancer. METHODS: We performed a systematic review and a meta-analysis based on random effect models to provide a pooled association measure. RESULTS: We subjected 8 studies (overall relative risks and 95% confidence intervals: 1.01, 0.72 to 1.43, I2 = 64.4%) to meta-analysis. Subgroup analysis revealed a marginally significant association between radon exposure and kidney cancer in studies conducted in Europe. Two population-based studies provided no evidence for the increased risk of kidney cancer in the general population. CONCLUSION: The association between radon and kidney cancer remains unclear but cannot be excluded because of its biological plausibility and the limited number and quality of existing studies. Additional data from the general population and well-designed miner cohort studies are needed to reveal the real relationship between radon exposure and kidney cancer.

Antimicrobial mechanism of epigallocatechin gallate and gallocatechin gallate: They target 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway.

The catechins EGCG and GCG show a variety of pharmacological activities, especially an antibacterial capacity, but their modes of antimicrobial action have not been fully elucidated. 1-Deoxy-d-xylulose 5-phosphate reductoisomerase (DXR), the first key enzyme in the MEP pathway for terpenoid biosynthesis, is a recently validated antimicrobial target. In order to disclose the antibacterial mechanism of EGCG and GCG, the DXR inhibitory activity of them was investigated in this study. The data show that EGCG and GCG both could specifically suppress the activity of DXR, with EGCG exhibiting relatively low effect against DXR (IC50 about 210 µM) and GCG displaying strong activity (IC50 27.5 µM). In addition, studies on inhibition kinetics of the catechins against DXR demonstrate that they are competitive inhibitors of DXR against DXP and uncompetitive inhibitors with respect to NADPH. Meanwhile, the possible interactions between DXR and the catechine, esyth onlols were simulated via docking experiments.

Inhibition of Orai1 Store-Operated Calcium Channel Prevents Foam Cell Formation and Atherosclerosis.

OBJECTIVE: To determine the role of orai1 store-operated Ca(2+) entry in foam cell formation and atherogenesis. APPROACH AND RESULTS: Acute administration of oxidized low-density lipoprotein (oxLDL) activates an orai1-dependent Ca(2+) entry in macrophages. Chelation of intracellular Ca(2+), inhibition of orai1 store-operated Ca(2+) entry, or knockdown of orai1 dramatically inhibited oxLDL-induced upregulation of scavenger receptor A, uptake of modified LDL, and foam cell formation. Orai1-dependent Ca(2+) entry induces scavenger receptor A expression and foam cell formation through activation of calcineurin but not calmodulin kinase II. Activation of nuclear factor of activated T cells is not involved in calcineurin signaling to foam cell formation. However, oxLDL dephosohorylates and activates apoptosis signal-regulating kinase 1 in macrophages. Orai1 knockdown prevents oxLDL-induced apoptosis signal-regulating kinase 1 activation. Knockdown of apoptosis signal-regulating kinase 1, or inhibition of its downstream effectors, JNK and p38 mitogen-activated protein kinase, reduces scavenger receptor A expression and foam cell formation. Notably, orai1 expression is increased in atherosclerotic plaques of apolipoprotein E(-/-) mice fed with high-cholesterol diet. Knockdown of orai1 with adenovirus harboring orai1 siRNA or inhibition of orai1 Ca(2+) entry with SKF96365 for 4 weeks dramatically inhibits atherosclerotic plaque development in high-cholesterol diet feeding apolipoprotein E(-/-) mice. In addition, inhibition of orai1 Ca(2+) entry prevents macrophage apoptosis in atherosclerotic plaque. Moreover, the expression of inflammatory genes in atherosclerotic lesions and the infiltration of myeloid cells into the aortic sinus plaques are decreased after blocking orai1 signaling. CONCLUSIONS: Orai1-dependent Ca(2+) entry promotes atherogenesis possibly by promoting foam cell formation and vascular inflammation, rendering orai1 Ca(2+) channel a potential therapeutic target against atherosclerosis.

Reduction of Intracellular Chloride Concentration Promotes Foam Cell Formation.

BACKGROUND: Previous work has demonstrated that the volume-regulated chloride channel is activated during foam cell formation, and inhibition of chloride movement prevents intracellular lipid accumulation. However, the mechanism explaining how chloride movement promotes foam cell formation is not clear. METHODS AND RESULTS: Foam cell formation was determined by Oil Red O staining. Western blotting and co-immunoprecipitation were used to examine protein expression and protein-protein interaction. [Cl(-)]iwas measured using 6-methoxy-N-ethylquinolinium iodide dye. The results showed that [Cl(-)]iwas decreased in monocytes/macrophages from patients with hypercholesterolemia and from apoE(-/-)mice fed with a high-fat diet. Lowering [Cl(-)]iupregulated scavenger receptor A (SR-A) expression, increased the binding and uptake of oxLDL, enhanced pro-inflammatory cytokine production and subsequently accelerated foam cell formation in macrophages from humans and mice. In addition, low Cl(-)solution stimulated the activation of JNK and p38 mitogen-activated protein kinases. Inhibition of JNK and p38 blocked Cl(-)reduced medium-induced SR-A expression and lipid accumulation. In contrast, reduction of [Cl(-)]ipromoted the interaction of SR-A with caveolin-1, thus facilitating caveolin-1-dependent SR-A endocytosis. Moreover, disruption of caveolae attenuated SR-A internalization, JNK and p38 activation, and ultimately prevented SR-A expression and foam cell formation stimulated by low Cl(-)medium. CONCLUSIONS: This data provide strong evidence that reduction of [Cl(-)]iis a critical contributor to intracellular lipid accumulation, suggesting that modulation of [Cl(-)]iis a novel avenue to prevent foam cell formation and atherosclerosis.

ClC-3 chloride channel/antiporter defect contributes to inflammatory bowel disease in humans and mice.

BACKGROUND: ClC-3 channel/antiporter plays a critical role in a variety of cellular activities. ClC-3 has been detected in the ileum and colon. OBJECTIVE: To determine the functions of ClC-3 in the gastrointestinal tract. DESIGN: After administration of dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzenesulfonic acid (TNBS), intestines from ClC-3-/- and wild-type mice were examined by histological, cellular, molecular and biochemical approaches. ClC-3 expression was determined by western blot and immunostaining. RESULTS: ClC-3 expression was reduced in intestinal tissues from patients with UC or Crohn's disease and from mice treated with DSS. Genetic deletion of ClC-3 increased the susceptibility of mice to DSS- or TNBS-induced experimental colitis and prevented intestinal recovery. ClC-3 deficiency promoted DSS-induced apoptosis of intestinal epithelial cells through the mitochondria pathway. ClC-3 interacts with voltage-dependent anion channel 1, a key player in regulation of mitochondria cytochrome c release, but DSS treatment decreased this interaction. In addition, lack of ClC-3 reduced the numbers of Paneth cells and impaired the expression of antimicrobial peptides. These alterations led to dysfunction of the epithelial barrier and invasion of commensal bacteria into the mucosa. CONCLUSIONS: A defect in ClC-3 may contribute to the pathogenesis of IBD by promoting intestinal epithelial cell apoptosis and Paneth cell loss, suggesting that modulation of ClC-3 expression might be a new strategy for the treatment of IBD.

Prevention of respiratory distress syndrome in preterm infants by antenatal ambroxol: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of antenatal ambroxol as a preventive therapeutic of respiratory distress syndrome (RDS) in preterm infants. METHODS: Randomized controlled trials of antenatal ambroxol treatment for RDS in preterm infants published up to March 2012 were downloaded from the Cochrane Library, PubMed, EMBASE, Science Citation Index, and Google Scholar databases. Data were evaluated for homogeneity and analyzed by the Cochrane Collaboration's RevMan software. RESULT: Twelve trials involving a total of 1335 premature infants were selected for meta-analysis. Neonatal RDS was lower in the ambroxol-treated group than in the groups treated with placebo (risk ratio [RR] = 0.38, 95% confidence interval [CI]: 0.24 to 0.59) or corticosteroids (RR = 0.49, 95% CI: 0.31 to 0.78). The ambroxol-treated group had lower risk of neonatal infection than the corticosteroid-treated group (RR = 0.36, 95% CI: 0.18 to 0.73). CONCLUSIONS: In cases of inevitable preterm birth, antenatal ambroxol is recommended over corticosteroids to prevent neonatal RDS. However, further research is necessary to determine the optimal treatment dosages and regimens of antenatal ambroxol to achieve consistent superior results over corticosteroids.

Visual Dysfunction is a Risk Factor of Postoperation Delirium in Parkinson Disease.

OBJECTIVE: To investigate the incidence of and factors influencing postoperative delirium (POD) in Parkinson disease after deep brain stimulation (DBS) surgery. METHODS: A total of 272 patients with Parkinson disease who underwent DBS completed the Visual Impairment in Parkinson Disease Questionnaire (VIPD-Q) and underwent neuro-ophthalmologic examinations including optical coherence tomography and fundus vessel analysis. We retrospect the prevalence of POD in groups with different VIPD-Q scores, retinal nerve fiber layer (RNFL) thicknesses, and vessel percentage areas (VPA). A predictive model based on the VIPD-Q was constructed using multivariate logistic regression and verified using bootstrap validation. RESULTS: POD was experienced by 65 (23.9%) of 272 patients. Patients with PD who had visual impairment (VIPD-Q > 6) had a higher incidence of POD (chi-square, P < 0.001). The thickness of the RNFL and VPA were also correlated with POD risk. Differences in implantation locations (subthalamic nucleus or pars interna of globus pallidus), operation times, and general anesthesia times did not affect the prevalence of DBS-related POD. A nomogram was constructed based on ophthalmic events to predict the risk of POD. CONCLUSIONS: The study findings provide convincing evidence of the relationship between visual dysfunction and the risk of POD. In view of the higher risk of POD, visually impaired patients with PD should undergo closer monitoring after DBS surgery.

Synthesis and Antibacterial Activity of Spiro[4H-pyran-3,3'-oxindoles] Catalyzed by Tröger's Base Derivative.

OBJECTIVE: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared via the one pot reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins and malononitrile successfully catalyzed by a Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]-1,5-diazadicyclo[3.3.1]-2,6-octadiene). The antibacterial activity of products against three wild-type bacteria (B. subtilis, S. aureus, and E. coli) and two resistant strains (Methicillin-resistant S. aureus (18H8) and E. coli carrying the BlaNDM-1 gene (18H5)) was evaluated using the minimum inhibitory concentration (MIC).. METHODS: 1-Phenyl-1,3-butanedione 2 or dibenzoylmethane 2' (0.42 mmol), substituted isatin 3 (0.4 mmol), malononitrile 4 (0.8 mmol), Tröger's base derivative 1b (0.08 mmol), and 10 mL of acetonitrile were added to a 50 mL round bottom flask and refluxed. After the completion (TLC monitoring), water (10 mL) was added to the reaction mixture; pH = 7 was adjusted with saturated NaHCO3 (aq.), and the mixture was extracted with CH2Cl2 (50 mL × 3). Organic layers were combined and dried with anhydrous Na2SO4; the solvent was removed under vacuum, and the residue was purified by column chromatography (VDCM: VMeOH = 80: 1) to afford product 5. The antibacterial activity was tested by the MTT method. RESULTS: Seventeen spiro[4H-pyran-3,3'-oxindole] derivatives were synthesized through the reaction of chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot in medium to high yields. Four compounds showed antibacterial activity, and two of them showed the same activity as the positive control Ceftazidime on S. aureus (MIC = 12.5 µg/mL). CONCLUSION: Two classes of spiro[4H-pyran-3,3'-oxindole] derivatives were prepared, and their antibacterial activity was evaluated. Tröger's base derivative 1b (5,12-dimethyl-3,10-diphenyl-bis-1H-pyrazol[b,f][4,5]- 1,5-diazadicyclo[3,3,1]-2,6-octadiene) was used as an efficient organocatalyst for the reaction of low reactive chain diketones (1-phenyl-1,3-butanedione or dibenzoyl methane), substituted isatins, and malononitrile in one-pot successfully and effectively by providing multiple active sites and alkaline environment. By the theoretical calculation, we explained the possible reaction sequence and mechanism. Due to the superiority and high efficiency of the TB framework as an organocatalyst, the reaction showed many advantages, including mild reaction conditions, low catalyst loading, and a wide substrate range. It expanded the application of Tröger's base to the multicomponent reaction in organocatalysis. Some products were screened due to their high antibacterial activity in vitro, showing their potential in new antibacterial drug development.

Awake rabbit model of ischemic spinal cord injury with delayed paraplegia: The role of ambient temperature.

BACKGROUND: Paraplegia after spinal cord ischemia is a devastating condition in the clinic. Here, we develop an awake rabbit model of spinal cord ischemia with delayed paraplegia and explore the influence of ambient temperature on the outcomes after injury. METHODS: A total of 47 male rabbits were involved in the present study. Transient spinal cord ischemia was induced by occluding the infrarenal abdominal aorta of awake rabbits at different ambient temperatures. To find the optimal conditions for developing delayed paraplegia, hindlimb motor function after ischemia was evaluated between experiments. RESULTS: The onset and magnitude of ischemic injury varied with the ambient temperature maintained during the peri-ischemia period. More serious spinal cord injury occurred when ischemia was induced at higher temperatures. At 18°C, 25-minute ischemia resulted in 74% of rabbits developing delayed paraplegia. At a temperature of 28°C or higher, most of the animals developed acute paraplegia immediately. While at 13°C, rabbits usually regained normal motor function without paraplegia. CONCLUSION: This awake rabbit model is highly reproducible and will be helpful in future studies of delayed paraplegia after spinal cord ischemia. The ambient temperature must be considered while using this model during investigation of therapeutic interventions.

Comprehensive assessment of the ecological risk of exposure to triphenyl phosphate in a bioindicator tadpole.

The toxicity of triphenyl phosphate (TPhP) to aquatic organisms in surface waters has been demonstrated; However, an understanding of toxicity profiles of TPhP in amphibians is limited. Therefore, the adverse effects and threshold concentrations of TPhP on metamorphosis, growth, locomotion, and hepatic antioxidants of Gosner stage 25 Polypedates megacephalus tadpoles under long-term (35 d) exposure to six TPhP concentrations until complete metamorphosis were assessed. Additionally, the overall effect of using integrated multiple biomarkers were determined to demonstrate the potential ecological risks of waterborne TPhP at environmentally relevant concentrations in amphibian tadpoles. With increasing TPhP concentrations, physical parameters (snout-vent length, body mass, condition factor, and hepatic somatic index), jumping distance, hepatic catalase, and superoxide dismutase activities decreased, whereas metamorphosis time and malondialdehyde content increased. The threshold concentration of TPhP that affected the tadpole biomarker, except for metamorphosis rate and jumping distance, was 50-400 µg/L. Furthermore, the standardized scores of the examined integrated biomarkers in the six TPhP concentrations were visualized using radar plots and calculated as the integrated biomarker responses (IBRs). The varying TPhP concentrations had different scores in the radar plots, and the threshold for affecting the IBR value was 10 µg/L, which was close to the TPhP concentration in surface waters. Additionally, IBR values were strongly positively correlated with the TPhP concentrations. These findings indicate that environmentally relevant exposure to waterborne TPhP can pose an ecological risk to amphibian tadpoles. This study can serve as a reference and assist in the formulation of relevant policies and strategies to control TPhP pollution in water bodies.

Ophthalmologic problems correlates with cognitive impairment in patients with Parkinson's disease.

Objective: Visual impairment is a common non-motor symptom (NMS) in patients with Parkinson's disease (PD) and its implications for cognitive impairment remain controversial. We wished to survey the prevalence of visual impairment in Chinese Parkinson's patients based on the Visual Impairment in Parkinson's Disease Questionnaire (VIPD-Q), identify the pathogens that lead to visual impairment, and develop a predictive model for cognitive impairment risk in Parkinson's based on ophthalmic parameters. Methods: A total of 205 patients with Parkinson's disease and 200 age-matched controls completed the VIPD-Q and underwent neuro-ophthalmologic examinations, including ocular fundus photography and optical coherence tomography. We conducted nomogram analysis and the predictive model was summarized using the multivariate logistic and LASSO regression and verified via bootstrap validation. Results: One or more ophthalmologic symptoms were present in 57% of patients with Parkinson's disease, compared with 14% of the controls (χ2-test; p < 0.001). The visual impairment questionnaire showed good sensitivity and specificity (area under the curve [AUC] = 0.918, p < 0.001) and a strong correlation with MoCA scores (Pearson r = -0.4652, p < 0.001). Comparing visual impairment scores between pre- and post-deep brain stimulation groups showed that DBS improved visual function (U-test, p < 0.001). The thickness of the retinal nerve fiber layer and vessel percentage area predicted cognitive impairment in PD. Interpretation: The study findings provide novel mechanistic insights into visual impairment and cognitive decline in Parkinson's disease. The results inform an effective tool for predicting cognitive deterioration in Parkinson's based on ophthalmic parameters.

The first complete mitochondrial DNA of the Chinese short-limbed skink (Ateuchosaurus chinensis Gray, 1845) determined by next-generation sequencing.

The complete mitochondrial DNA (mtDNA) for the Chinese short-limbed skink (Ateuchosaurus chinensis Gray, 1845) was described by using next-generation sequencing. The total length of mtDNA was 16,840 bp, which contained 13 PCGs (COI-III, ND1-6, ND4L, ATP6, ATP8, and CYTB), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and a control region (D-loop). The Bayesian inference tree showed that A. chinensis was a sister taxon to other scincid lizards in genera of Scincella, Isopachys, Sphenomorphus and Tropidophorus. The complete mtDNA of A. chinensis will be an important genetic resource to the studies of conservation and restoration of A. chinensis.

[Distribution, Sources, and Risk Assessment of Polyfluoroalkyl Substances in Main Rivers and Soils of Tianjin].

Rapid urbanization and industrialization may potentially impact the spatial distribution and transmission of polyfluoroalkyl substances (PFASs). Tianjin, a typical industrialized city with a high urbanization level around Bohai Bay, was selected to evaluate the spatial distribution and ecological risks of PFASs. Water and soil samples were systematically collected and analyzed by using solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS-MS) methods. The results showed that all 12 PFASs were detected in water and soils, and the detection rates of the other congeners were low. The concentrations of ΣPFASs in water ranged from 3.93 to 357.85 ng ·L-1, and the levels of ΣPFASs in soils ranged from 4.60 to 63.85 ng ·g-1. PFBA was the major component in water and soils, and the contribution of PFBA was 37% and 67% in water and soils, respectively. The spatial difference in ΣPFASs in the water bodies was significant. ΣPFAS concentrations in the surface water were higher in the north (mean value of 63.83 ng ·L-1) than in the south (mean value of 51.71 ng ·L-1) and higher in the eastern coastal area (mean value of 71.36 ng ·L-1) than in the western area (mean value of 36.08 ng ·L-1). ΣPFAS concentrations from upstream to downstream of the rivers showed an increasing trend. The highest PFAS concentration was found in the Chaobai River, and the lowest was detected in the South Canal. The spatial distribution of PFASs in soils was higher in the south (mean value of 13.33 ng ·g-1) than in the north (mean value of 6.38 ng ·g-1) and higher in the eastern coastal region (mean value of 11.45 ng ·g-1) than in the western region (mean value of 6.94 ng ·g-1). The soil concentrations of ΣPFASs in the Haihe River Basin were the highest. The source analysis results showed that the emulsification of rubber products, food packaging process, paper surface treatment, fire extinguishing agent use, and electrochemical fluorination process in industrial production were the main sources of PFASs in the soils in the study area. PFOS/PFOA, PFOA/PFNA, and PFHpA/PFOA analyses showed that the main source of PFASs in water bodies was the degradation of precursors. ΣPFASs in a few areas originated from the direct emissions from production, but the atmospheric deposition was small. The results of the ecological risk evaluation indicated that the exposure concentrations of PFASs in water and soils in the study area were at a low ecological risk level. However, the long-term ecological effects of PFASs cannot be ignored because of their long-distance transport capability and high food chain (web) accumulation capability.

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients.

Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.