Graph theoretical analysis and independent component analysis of diabetic optic neuropathy: A resting-state functional magnetic resonance imaging study.

AIMS: This study aimed to investigate the resting-state functional connectivity and topologic characteristics of brain networks in patients with diabetic optic neuropathy (DON). METHODS: Resting-state functional magnetic resonance imaging scans were performed on 23 patients and 41 healthy control (HC) subjects. We used independent component analysis and graph theoretical analysis to determine the topologic characteristics of the brain and as well as functional network connectivity (FNC) and topologic properties of brain networks. RESULTS: Compared with HCs, patients with DON showed altered global characteristics. At the nodal level, the DON group had fewer nodal degrees in the thalamus and insula, and a greater number in the right rolandic operculum, right postcentral gyrus, and right superior temporal gyrus. In the internetwork comparison, DON patients showed significantly increased FNC between the left frontoparietal network (FPN-L) and ventral attention network (VAN). Additionally, in the intranetwork comparison, connectivity between the left medial superior frontal gyrus (MSFG) of the default network (DMN) and left putamen of auditory network was decreased in the DON group. CONCLUSION: DON patients altered node properties and connectivity in the DMN, auditory network, FPN-L, and VAN. These results provide evidence of the involvement of specific brain networks in the pathophysiology of DON.

Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Ocular microvascular alteration in patients with myocardial infarction-a new OCTA study.

Myocardial infarction is defined as a sudden decrease or interruption in blood flow to the coronary arteries, causing ischemic necrosis of the corresponding cardiomyocytes. It is unclear whether systemic macrovascular alterations are associated with retinal microvascular changes. This study utilized optical coherence tomography angiography (OCTA) to compare variations in conjunctival vascular density and fundus retinal vessel density between patients with myocardial infarction (MI) and healthy controls. This study recruited 16 patients (32 eyes) with MI and 16 healthy controls (32 eyes). The superficial retinal layer (SRL), deep retinal layer (DRL) and conjunctival capillary plexus in each eye were evaluated by OCTA. Parameters measured included the density of the temporal conjunctival capillary, retinal microvascular (MIR) and macrovascular (MAR) alterations and total MIR (TMI). The microvascular density of each retinal region was evaluated by the hemisphere segmentation (SR, SL, IL, and IR), annular partition (C1, C2, C3, C4, C5 and C6), and modified early treatment of diabetic retinopathy study (R, S, L, and I) methods. In the macular area, the superficial and deep retinal microvascular densities displayed notable variations. In the superficial layers, the superficial TMI, superficial MIR, and superficial MAR, as well as densities in the SL, IL, S, L, C1, C2, C5 and C6 regions, were significantly lower in MI patients (p < 0.05 each). In the deep layers, the deep MIR and deep TMI), as well as densities in the SL, IL, L, C1, C2 and C6 regions were significantly lower in MI patients (p < 0.05 each). In contrast, the conjunctival microvascular density was significantly higher in MI patients than in healthy controls (p < 0.001). The microvascular densities measured in the deep and superficial retinal layers and in the conjunctiva differ in MI patients and healthy controls. OCTA is effective in detecting changes in the ocular microcirculation.

Over-expression of UDP-glycosyltransferase UGT353G2 confers resistance to neonicotinoids in whitefly (Bemisia tabaci).

The whitefly, Bemisia tabaci, comes up high metabolic resistance to most neonicotinoids in long-term evolution, which is the key problem of pest control. UGT glycosyltransferase, as a secondary detoxification enzyme, plays an indispensable role in detoxification metabolism. In this study, UGT inhibitors, 5-nitrouracil and sulfinpyrazone, dramatically augmented the toxic damage of neonicotinoids to B. tabaci. A UGT named UGT353G2 was identified in whitefly, which was notably up-regulated in resistant strain (3.92 folds), and could be induced by most neonicotinoids. Additionally, the using of RNA interference (RNAi) suppresses UGT353G2 substantially increased sensitivity to neonicotinoids in resistant strain. Our results support that UGT353G2 may be involved in the neonicotinoids resistance of whitefly. These findings will help further verify the functional role of UGTs in neonicotinoid resistance.

Novel_miR-1517 mediates CYP6CM1 to regulate imidacloprid resistance in Bemisia tabaci (Hemiptera: Gennadius).

Bemisia tabaci (Hemiptera: Gennadius) is a notorious pest that is capable of feeding on >600 kinds of agricultural crops. Imidacloprid is critical in managing pest with sucking mouthparts, such as B. tabaci. However, the field population of B. tabaci has evolved resistance because of insecticide overuse. The overexpression of the detoxification enzyme cytochrome P450 monooxygenase is considered the main mechanism of imidacloprid resistance, but the mechanism underlying gene regulation remains unclear. MicroRNAs are a type of endogenous small molecule compounds that is fundamental in regulating gene expression at the post-transcriptional level. Whether miRNAs are related to the imidacloprid resistance of B. tabaci remains unknown. To gain deep insight into imidacloprid resistance, we conducted on miRNAs expression profiling of two B. tabaci Mediterranean (MED) strains with 19-fold resistance through deep sequencing of small RNAs. A total of 8 known and 1591 novel miRNAs were identified. In addition, 16 miRNAs showed significant difference in expression levels between the two strains, as verified by quantitative reverse transcription PCR. Among these, novel_miR-376, 1517, and 1136 significantly expressed at low levels in resistant samples, decreasing by 36.9%, 60.2%, and 15.6%, respectively. Moreover, modulating novel_miR-1517 expression by feeding with 1517 inhibitor and 1517 mimic significantly affected B. tabaci imidacloprid susceptibility by regulating CYP6CM1 expression. In this article, miRNAs related to imidacloprid resistance of B. tabaci were systematically screened and identified, providing important information for the miRNA-based technological innovation for this pest management.

Knockdown of the Nicotinic Acetylcholine Receptor ß1 Subunit Decreases the Susceptibility to Five Neonicotinoid Insecticides in Whitefly (Bemisia tabaci).

The sweet potato whitefly, Bemisia tabaci, (Gennadius) (Hemiptera:Aleyrodidae) is a global pest of crops. Neonicotinoids are efficient insecticides used for control of this pest. Insecticidal targets of neonicotinoids are insect nicotinic acetylcholine receptors (nAChRs). Here, we characterized and cloned the full length of the nAChR ß1 subunit (BTß1) in B. tabaci and confirmed the consistency of BTß1 in B. tabaci MEAM1 and MED. Expression levels of BTß1 in different developmental stages and body parts of adults were investigated and compared in B. tabaci MED. dsRNA was prepared to knock down BTß1 in adult B. tabaci and significantly decreases the susceptibility to five neonicotinoid insecticides, including imidacloprid, clothianidin, thiacloprid, nitenpyram, and dinotefuran. This study indicated BTß1 as a notable site influencing the susceptibility of B. tabaci to neonicotinoids.

Lack of pharmacokinetic interaction between derazantinib and naringin in rats.

CONTEXT: Derazantinib-an orally bioavailable, ATP competitive, multikinase inhibitor-has strong activity against fibroblast growth factor receptors (FGFR)2, FGFR1, and FGFR3 kinases. It has preliminary antitumor activity in patients with unresectable or metastatic FGFR2 fusion-positive intrahepatic cholangiocarcinoma (iCCA). OBJECTIVE: This experiment validates a novel sensitive and rapid method for the determination of derazantinib concentration in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), and applies it to the study of drug-drug interaction between derazantinib and naringin in vivo. MATERIALS AND METHODS: A Xevo TQ-S triple quadrupole tandem mass spectrometer was used for mass spectrometry monitoring in selective reaction monitoring (SRM) mode with transitions of m/z 468 96 → 382.00 for derazantinib and m/z 488.01 → 400.98 for pemigatinib, respectively. The pharmacokinetics of derazantinib (30 mg/kg) was investigated in Sprague-Dawley (SD) rats divided into two groups (with the oral pretreatment of 50 mg/kg naringin or not). RESULTS: The newly optimized UPLC-MS/MS method was suitable for the determination of derazantinib in rat plasma. It was also successfully employed to evaluate the effect of naringin on derazantinib metabolism in rats. After pretreatment with naringin, there was no significant difference in the pharmacokinetic parameters (AUC0→t, AUC0→∞, t1/2, CLz/F, and Cmax) of derazantinib when compared with derazantinib alone. CONCLUSION: Co-administration of naringin with derazantinib was not associated with significant changes in pharmacokinetic parameters. Thus, this study suggests that the combination of derazantinib with naringin can safely be administered concomitantly without dose adjustment.

Alternation of brain intrinsic activity in patients with hypertensive retinopathy: a resting-state fMRI study.

OBJECTIVE: To investigate the changes of amplitude of low-frequency fluctuation (ALFF) in brain regions of patients with hypertensive retinopathy by using resting-state functional magnetic resonance imaging (rs-fMRI) and change in the relationship of ALFF value with potential emotional and psychological changes. METHODS: Thirty-one patients with hypertensive retinopathy (HR) (16 men and 15 women) and 31 healthy controls (HCs; 16 men and 15 women) matched for age, sex, and weight were enrolled in the research. The changes in mean ALFF values could reflect brain activity between HR patients and HCs. We used the independent samples t-test to evaluate different demographic and general information between the two groups. Two-sample t-test was used to detect differences of mean ALFF values in the brain region between the two groups using the same software. RESULTS: The ALFF values in the brain areas of HR and HCs were different. HR patients had lower ALFF value in the left medial superior frontal gyrus and left middle frontal gyrus than the HCs. The higher ALFF values were found in the cerebellum (left inferior and right superior lobes, vermis) and left inferior temporal gyrus of the HR patients than the controls. CONCLUSION: Our findings showed fluctuations in ALFF values in the HR patients' brain regions. ALFF values reflect over or reduced activity in brain regions. Abnormal ALFF values in these brain areas can predict early HR development, preventing the malignant transformation of hypertensive microangiopathy.

Bi4O(I3O10)(IO3)3(SeO4): trimeric condensation of IO43- monomers into the I3O105- polymeric anion observed in a three-component mixed-anion NLO material.

A novel mixed-anion NLO crystal, namely, Bi4O(I3O10)(IO3)3(SeO4), containing a brand-new "pinwheel-like" I3O105- polyiodate anion group was constructed from the trimeric condensation of IO43- monomers. Bi4O(I3O10)(IO3)3(SeO4) exhibits a complex 3D topological structure and gives a moderate second harmonic generation (SHG) signal about 1.1 times that of KH2PO4 (KDP).

Highly Efficient Cuprous Complexes with Thermally Activated Delayed Fluorescence for Solution-Processed Organic Light-Emitting Devices.

Two mononuclear cuprous complexes [Cu(PNNA)(POP)]BF4 (1) and [Cu(PNNA)(Xantphos)]BF4 (2) (PNNA = 9,9-dimethyl-10-(6-(3-phenyl-1H-pyrazol-1-yl)pyridin-3-yl)-9,10-dihydroacridine, POP = bis[2-(dipenylphosphino)phenyl]ether, Xantphos =4,5-bis(diphenylphosphino)-9,9-dimethylxanthene), with intense bluish-green luminescence based on a new diimine ligand were designed and synthesized. Their structural, electrochemical, and photophysical properties were characterized by single-crystal X-ray analysis, cyclic voltammetry, temperature dependence of spectroscopy, time-dependent emission spectroscopy, etc. The complexes exhibit high photoluminescence quantum yields in doped films (up to 74.6%) at room temperature. Thermally activated delayed fluorescence based on intraligand charge transfer was observed by grafting a strong electron-donor moiety, 9,9-dimethylacridan, on the diimine ligand, which is supported by the density functional theory calculations on two complexes. Highly efficient solution-processed OLEDs based on these two complexes were fabricated, among which the electroluminescent device using 2 as dopant shows a peak external quantum efficiency of 7.42%, a peak current efficiency of 20.24 cd/A, and a maximum brightness of 5579 cd/m(2).

[Medicinal-powder-separated Long-snake Moxibustion over the Governor Vessel with Different Skin Vesiculation Conditions for Treatment of Patients with Rheumatoid Arthritis].

OBJECTIVE: To observe the curative effect of herbal-medicine -powder-separated "Long-snake moxibustion" over the Governor Vessel at different vesiculation conditions in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120 RA patients received herbal-powder-separated long-snake moxibustion in the present study and randomized into Banmao (Cantharides, CANT, being able to promote skin vesiculation for enhancing the therapeutic effect)-0 g group, CANT-1.5 g group and CANT-3.0 g group (n=40 in each group) according to the dosage of CANT used in the herbs-medicinal powder. In addition to Cantharides, the medicinal powder also contained Shexiang (Moschus, 1 g), Dingxiang (Flos Caryophylli,1 g) and Rougui (Cinnamon bark,1 g). When treated, the patient was asked to take a prone position, the ginger juice was evenly smeared on the patient's back from Dazhui (GV 14) to Yaoshu (GV 2, about 3 cm wide), then, the above-mentioned medicinal powder was spread on the smeared ginger juice, followed by putting a layer of gauze, ginger powder and ignited moxa-stick, respectively. The treatment was conducted once every 30 days, and twice altogether. The visual analog scale (VAS) was used to assess the pain seve-rity of moxibustion-induced skin vesiculation on the patient's back in 24 h after moxibustion. The severity of vesiculation was assessed according to the status of vesicles appeared at the local skin (0 point:no vesicles;3 points:string-of-beads-like vesicles with the vesicle diameter being less than 2 cm; 6 points:foliated vesicles with the vesicle diameter being larger than 2 cm). The patient's symptoms and dysfunction of hand-knee joints were scored, and serum rheumatoid factor (RF), C-reactive protein (CRP), immune globulin IgM and IgG contents were assayed by ELISA, and the erythrocyte sedimentation rate (ESR) was determined by using Westergren method. RESULTS: After moxibustion, of the three 40 RA patients in the CANT-0 g, CANT-1.5 g and CANT-3.0 g groups, 0, 10 and 12 cases were under control in their symptoms, 7, 16 and 19 experienced marked improvement, 17, 9 and 6 were improved, 16, 5 and 3 failed in the treatment, with the effective rates being 60.0%(16/40), 87.5%(35/40) and 92.5%(37/40), respectively. The curative effects of CANT-1.5 g and CANT-3.0 g were significantly superior to that of CANT-0 g (P<0.01). Both the scores for skin vesiculation status and pain severity were significantly higher in the CANT-3.0 g group than in the CANT-0 g (no skin vesiculation) and CANT-1.5 g groups, and markedly higher in the CANT-1.5 g group than in the CANT-0 g group (P<0.01). Following the treatment, the symptom score and joint dysfunction score, ESR level, and serum RF, CRP, IgM and IgG contents were considerably decreased in the three groups in comparison with pre-treatment in the same one group (P<0.01); and those of the CANT-1.5 g and CANT-3.0 g groups were markedly lower than those of CANT-0 g group (P<0.01). In addition, CANT-3.0 g was notably superior to CANT-1.5 g in lowering symptom and joint dysfunction scores, ESR, serum RF and CRP contents (P<0.05). No significant differences were found between the CANT-1.5 g and CANT-3.0 g groups in serum IgM and IgG levels and in the therapeutic effect (P>0.05). CONCLUSIONS: Long-snake moxibustion combined with CANT-induced vesiculation has a good curative effect in the treatment of RA, which may be associated with its effects in lo-wering ESR level, and serum RF, CRP, IgM and IgG contents. The curative effect of vesiculation moxibustion is far better than non-vesiculation moxibustion, but mild vesiculation moxibustion is recommended due to severe pain of CANT-3.0 g.

Altered proteomic pattern in platelets of rats with sepsis.

Platelet dysfunction and thrombocytopenia are common responses to sepsis, but how sepsis changes platelet function is not completely understood. This is due, in part, to our lack of understanding of how sepsis alters platelet protein patterns. The aim of the present study, accordingly, was to investigate the response of the platelet proteome to sepsis. We applied proteomic technology to analyze platelet samples of rats with sepsis. Rats were divided into two groups: 1) sham surgery and 2) sepsis induced by cecal ligation and puncture (CLP) surgery. Platelet samples were collected from surviving rats 12 and 24h after surgery, and platelet proteins were separated by two-dimensional electrophoresis (2-DE). Differentially expressed proteins were identified by mass spectrometry (MS). In the CLP group, there were 20 spots that were statistically significantly different at 12h. Of these spots, 16 spots were increased and four spots were decreased. At 24h, there were six spots increased in the CLP group. Of the 26 spots, 12 proteins associated with platelet activation, acute phase proteins, cytoskeleton structure, and energy production were identified. Of interest, alpha-1-antitrypsin precursor (AAT) and ATP synthase beta subunit (ATPB) were both increased at 12 and 24h of sepsis by 2-DE and immunoblotting. By providing the platelet profiles, our results demonstrate that this proteomic approach brings us closer to understanding how platelet dysfunction develops after sepsis.

Intrathecal administration of triptolide, a T lymphocyte inhibitor, attenuates chronic constriction injury-induced neuropathic pain in rats.

Triptolide is a potent immunosuppressive drug capable of inhibiting T cell activation and proliferation. Recent studies show that T cells play an important role in neuropathic pain following nerve injury in rats. In this study, we investigated the effect of triptolide on T cell activation and development of neuropathic pain. Neuropathic pain by chronic constriction injury (CCI) was induced by loose ligation of the sciatic nerve in Sprague-Dawley rats. Triptolide (5 or 10 µg/kg) or vehicle (DMSO) was administered intrathecally after surgery for 7 days (n=8 per group). The right hind paw withdrawal threshold to von Frey filament stimuli and withdrawal latency to radiant heat were determined before and after the surgery (days 0 to 7). NF-κB activation and pro-inflammatory cytokine (TNF-α and IL-2) expression were determined by ELISA, Western blot, and real time-PCR. CCI of the sciatic nerve induced mechanical allodynia and thermal hyperalgesia in these rats. Intrathecal triptolide (5 and 10 µg/kg) suppressed the development of allodynia and thermal hyperalgesia. It also inhibited CCI-induced inflammation and T cell activation, by decreasing spinal cord TNF-α, IL-2 and NF-κB p65 levels. Motor dysfunction was not observed after triptolide treatment. In the present study, we demonstrated the suppressive effect of triptolide on the development of neuropathic pain. Therefore, triptolide could be a promising immunosuppressive agent in the treatment of neuropathic pain. Further studies are required to examine the safety of intrathecal triptolide for clinical application.

Protective effects of the free radical scavenger edaravone on acute pancreatitis-associated lung injury.

Impaired lung function is the primary contributor to most deaths associated with severe acute pancreatitis. It is widely accepted that oxidative stress plays a central role in the pathogenesis of pancreatitis and associated complications. Therefore, in the present study, we investigated whether therapeutic treatment with the free radical scavenger edaravone could protect rats against acute pancreatitis and the associated lung injury. Acute pancreatitis was induced by infusion of 1ml/kg of sodium taurocholate (3% solution) into the biliopancreatic duct. Edaravone (8mg/kg) was administered 1h and 13h after inducing pancreatitis, the severity of pancreatic and pulmonary injuries was evaluated 24h after inducing pancreatitis. Edaravone treatment significantly reduced the elevated malondialdehyde levels in rat lungs after acute pancreatitis, suggesting an important role for free radicals in acute pancreatitis-associated lung injury. In addition, edaravone showed significant protective effects against neutrophil infiltration and tissue injury in both pancreas and lung, as demonstrated by serum amylase levels, myeloperoxidase activity and histopathological analysis. Edaravone treatment also attenuated the elevated mRNA levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in rat lungs after acute pancreatitis. In conclusion, edaravone protects rats against acute pancreatitis-associated lung injury, probably through its antioxidant and anti-inflammatory effects. Thus, edaravone shows promise as a treatment for lung injury in patients with acute pancreatitis.