Introduction Itch is a common symptom of many skin and systemic diseases. Identifying novel endogenous itch mediators and the downstream signaling pathways involved will contribute to the development of new strategies for the treatment of chronic itch. In the present study, we adopted behavioral testing, patch clamp recording and metabonomics analysis to investigate the role of agmatine in itch and the underlying mechanism. Methods Behavioral analysis was used to evaluate the establishing of acute and chronic itch mice model, and to test the effects of different drugs or agents on mice itch behavior. Western blotting analysis was used to test the effect of agmatine on phosphorylation of ERK (p-ERK) expression in the spinal cord. Patch clamp recording was used to determine the effect agmatine on the excitability of DRG neurons and the role of ASIC3. Finally, the metabonomics analysis was performed to detect the concentration of agmatine in the affected skin under atopic dermatitis or psoriasis conditions. Results We fused a mouse model and found that an intradermal injection of agmatine (an endogenous polyamine) into the nape of the neck or cheek induced histamine-independent scratching behavior in a dose-dependent manner. In addition, the ablation of nociceptive C-fibers by resiniferatoxin (RTX) abolished agmatine-induced scratching behavior. However, agmatine-induced itch was not affected by the pharmacological inhibition of either transient receptor potential vanilloid 1 (TRPV1) or transient receptor potential ankyrin 1 (TRPA1); similar results were obtained from TRPV1−/− or TRPA1−/− mice. Furthermore, agmatine-induced itch was significantly suppressed by the administration of acid-sensing ion channel 3 (ASIC3) inhibitors, APETx2 or amiloride. Agmatine also induced the upregulation of p-ERK in the spinal cord; this effect was inhibited by amiloride. Current clamp recording showed that the acute perfusion of agmatine reduced the rheobase and increased the number of evoked action potentials in acute dissociated dorsal root ganglion (DRG) neurons while amiloride reversed agmatine-induced neuronal hyperexcitability. Finally, we identified significantly higher levels of agmatine in the affected skin of a mouse model of atopic dermatitis (AD) when compared to controls, and the scratching behavior of AD mice was significantly attenuated by blocking ASIC3. Discussion Collectively, these results provide evidence that agmatine is a novel mediator of itch and induces itch via the activation of ASIC3. Targeting neuronal ASIC3 signaling may represent a novel strategy for the treatment of itch.
Controlled polymerization of cumulenic monomers represents a promising yet underdeveloped strategy toward well-defined alkyne polymers. Here we report a stereoelectronic effect-inspired approach using simple vinylidenecyclopropanes (VDCPs) as butatriene homologues in controlled radical ring-opening polymerizations. While being thermally stable, VDCPs mimic butatrienes via conjugation of the cyclopropane ring. This leads to exclusive terminal-selective propagation that affords a highly structurally regular alkyne-based backbone, featuring complete ring-opening and no backbiting regardless of polymerization conditions.
Controlling the composition and sequence during diazo copolymerization with vinyl or acetylenic monomers is highly desired yet challenging. Here we report a new base-metal-catalysis strategy to address this problem via tandem coupling/polymerization. A selective Cu-catalyzed C(3 + 1) copolymerization reaction was developed using propargyl carbonates and aryldiazomethanes derived from N-tosylhydrazones as the C3 and C1 building blocks, respectively. This reaction rapidly produces alternating-like poly(1,4-diaryl-2-butyne-1,4-diyl)s (Mn up to 31.0 kg/mol) in a modular fashion, without detectable homopolymer segments. This work provides a new avenue for the synthesis of hydrocarbon polymers through diazo copolymerization.
Luoyuan Bay is a mariculture influenced water body located in southeastern China. Multi-statistical techniques were applied to 21 sampling locations in the bay to identify the sources of microplastics and other pollutants in the sediment. In microplastics detection, fragment was the most abundant shape (~36%), and rayon was the dominant polymer (~59%). The size of more than 48% of total microplastics observed was less than 200 μm. The study showed that the upper part of Luoyuan Bay was dominated by microplastic pollution, while the lower part of the bay was dominated by persistent organic pollutants (PAHs, OCPs). Mariculture is one of the main sources of pollution in Luoyuan Bay. Apart from mariculture, there were additional sources such as industry, land reclamation, port, and so on; industry and land reclamation were the leading sources of microplastics, while port, industry, and mariculture were the primary sources of PAHs and OCPs.
Here we report a copper-catalyzed formal dehydration polymerization of propargylic alcohols. Copper catalysis allows for efficient in situ generation of [n]cumulenes (n = 3, 5) by a soft deprotonation/β-elimination pathway and subsequent polymerization via organocopper species. Alkyne polymers (Mn up to 36.2 kg/mol) were produced with high efficiency (up to 95% yield) and excellent functional group tolerance. One-pot synthesis of semiconducting head-to-head poly(phenylacetylene) was demonstrated through a polymerization-isomerization sequence.
The operation of traumatic cataract is a complicated operation. After severe ocular trauma, corneal edema or scar, posterior synechia of iris, bloody or inflammatory aqueous humor make it difficult to observe the lens and vitreous body under slit lamp microscope. Special examination and evaluation of the affected eyes before traumatic cataract surgery is helpful for surgeons to formulate surgical strategies, avoid intraoperative complications and predict postoperative visual quality. CT are used to exclude intraocular foreign bodies before operation, B-Scan and color doppler ultrasound are used to understand the overall condition of the eyeball, 20 MHz B-Scan is used to evaluate the integrity of the posterior capsule of the lens, and ultrasound biomicroscopy (UBM) is used to observe the condition of the lens zonule. With the development of optical instruments, anterior segment optical coherence tomography (AS-OCT), swept source optical coherence tomography (SS-OCT) and Scheimpflug imaging are also helpful to the preoperative evaluation of traumatic cataract. This article will review the preoperative evaluation of traumatic cataract.
Here, we describe the unexpected discovery of a Cu-catalyzed condensation polymerization reaction of propargylic electrophiles (CPPE) that transforms simple C3 building blocks into polydiynes of C6 repeating units. This reaction was achieved by a simple system composed of a copper acetylide initiator and an electron-rich phosphine ligand. Alkyne polymers (up to 33.8 kg/mol) were produced in good yields and exclusive regioselectivity with high functional group compatibility. Hydrogenation of the product afforded a new polyolefin-type backbone, while base-mediated isomerization led to a new type of dienyne-based electron-deficient conjugated polymer. Mechanistic studies revealed a new α-α selective Cu-catalyzed dimerization pathway of the C3 unit, followed by in situ organocopper-mediated chain-growth propagation. These insights not only provide an important understanding of the Cu-catalyzed CPPE of C3, C4, and C6 monomers in general but also lead to a significantly improved synthesis of polydiynes from simpler starting materials with handles for the incorporation of an α-end functional group.
Here we report the design, preparation, synthetic utility, and sensing application of a class of proaromatic structures, namely bicyclo[2.2.0]hexene (BCH) derivatives. Building on a valence isomerism concept, they feature modular and easy synthesis as well as high thermal stability, and can be oxidatively activated under mild conditions. New alkyl transfer reactions using BCHs as a radical donor have been developed to showcase the utility of their proaromaticity. Moreover, the redox-triggered valence isomerization of a quinoline-derived BCH led to colorimetric and fluorescent responses toward vapors of electrophilic reagents in solution and solid phase, respectively. This optical response was shown to involve a 1,3-cyclohexadiene structure that possesses an intramolecular charge transfer excited state with interesting aggregation induced emission (AIE) character. Thus, the potential of BCHs has been demonstrated as a versatile platform for the development of new reagents and functional materials.
Background To compare the accuracy of low-frequency ultrasound biomicroscopy (LFUBM) and 14-MHz ultrasonography with tissue harmonic imaging (14-MHz + THI) in the assessment of posterior capsule (PC) integrity in patients with traumatic cataracts (TCs). Methods From January 2019 to October 2020, 51 patients (51 eyes) with TCs who were scheduled for cataract extraction and for whom the PC of the lens could not be observed by the slit lamp visited Tianjin Eye Hospital, including 47 patients (47 eyes) with a penetrating injury of the eyeball and 4 patients (4 eyes) with a blunt injury of the eyeball. All eyes underwent LFUBM and 14-MHz + THI examinations before cataract extraction to determine the integrity of the PC. The integrity of the PC observed in surgery was the actual findings, and the consistency between the 2 methods was assessed in terms of the preoperative examination and intraoperative findings. Fisher’s exact test was used for consistency analysis, and P < 0.05 was considered statistically significant. Results Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were actual findings in surgery. Thirty eyes with ruptured PCs and 21 eyes with intact PCs were examined by LFUBM. Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were examined by 14-MHz + THI. There were no significant differences between the 2 methods and the intraoperative findings (P = 0.293 LFUBM, P = 0.623 14-MHz + THI). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LFUBM and 14-MHz + THI were 91 and 94%, 95 and 89%, 97 and 94%, 86 and 89% and 92 and 92%, respectively. Conclusions Both LFUBM and 14-MHz + THI were proved to have high levels sensitivity and specificity in diagnosing the status of the PC in TC and they can be used as accurate diagnostic tool in these cases.
[1,2]-Radical Brook rearrangement (RBR) has been identified as a viable pathway in M–H (M = Co, Fe) catalyzed hydrogen-atom-transfer reactions involving unsaturated acylsilanes. Guided by the same concept, we have explored two transformations, namely, a Co-catalyzed cycloisomerization reaction and a Fe-catalyzed cyclization/Giese addition reaction. Both reactions involve the generation of a versatile α-siloxy radical intermediate via concomitant philicity inversion and radical translocation, which is mechanistically distinct from coupling reactions involving fragmentation/reduction pathways. Synthesis of cyclic silyl enol ethers and sterically congested cyclopentanol derivatives have been thus achieved with high regio- and diastereo-selectivity.
Purpose. To report the application of 14-MHz ultrasonography with tissue harmonic imaging (14 MHz + THI) to determine the integrity of the posterior capsule (PC) in traumatic cataract (TC). Methods. Patients with TC who were scheduled to undergo cataract extraction and whose PC could not be observed by slit lamp examination were included in the study. The status of the PC was determined by 14 MHz + THI before cataract extraction and confirmed during surgery. The results regarding PC integrity obtained from 14 MHz + THI and intraoperative direct observation were compared. Result. The study enrolled 52 eyes of 52 patients (49 men and 3 women), with a mean age of 42.15 years ± 11.23 (SD). The nature of the trauma was blunt (3 eyes) or sharp (49 eyes). The 14 MHz + THI method showed 21 PCs to be intact and 31 to have ruptured before cataract surgery. During surgery, 23 PCs were observed to be intact, while 29 PCs were ruptured. 27 PCs were ruptured and 19 were intact, as determined by the two methods. The 14 MHz + THI observations were consistent with the intraoperative observations of the PC (kappa = 0.764), with no significant difference between the two methods (P=0.687). The sensitivity, specificity, and accuracy of 14 MHz + THI for observation of the PC were 93.10%, 82.60%, and 88.46%, respectively. Conclusion. The 14 MHz + THI method can accurately reveal the integrity of the PC in TC. It has important clinical value in the selection of cataract surgery methods and the prediction of complications during TC surgery.
Objective To observe the changes ofmacular structure and choroidal capillary blood flow density in patients with acute central serous chorioretinopathy (CSC).Methods Prospective cross-sectional study.A total of 24 eyes of 24 patients with monocular acute CSC (case group) diagnosed by clinical examination from Shanxi Eye Hospital during January and March 2018 were included in the study.The eyes (24 eyes) and contralateral eyes (24 eyes) of the patients in the case group were set to CSC group and contralateral eye group,respectively.Twenty-one eyes of 21 healthy volunteers with age and gender matching were selected as normal control group.The macular structure of the eyes were observed by OCT and OCT angiography (OCTA),and the blood vessel density of choroidal capillary layer in the circular area of the macular area with a radius of 1 mm was measured.The paired t-test was used to compare the differences in blood flow density in the choroidal capillaries between the three groups.Results The results of OCT showed that the serous neuroepithelial detachment in the macular area was observed in all eyes of the CSC group,with or without RPE detachment being 20 or 4 eyes,respectively.Of the 24 eyes in the contralateral eye group,13 eyes (54.2%) had thick choroidal RPE lesions (PPE).There was no abnormality in the retina and choroidal structure in the macular area of the normal control group.The results of OCTA showed that the blood flow density of choroidal capillaries in the CSC group,the contralateral eye group and the normal control group were 1.759 ± 0.132,1.924± 0.463,and 1.940± 0.033,respectively.Compared with the eyes of the contralateral eye group and the normal control group,the blood flow density of choroidal capillaries in the CSC group was significantly lower (t=6.611,6.474;P=0.000,0.000).There was no significant difference in the blood flow density of choroidal capillary layer between the contralateral eye group and the normal control group (t=1.328,P > 0.05).In the contralateral eye group,there was no significant difference in the blood flow density of choroidal capillary layer between PPE eyes and no RPE eyes (t=0.806,P>0.05).Conclusions There is 54.2% of the contralateral eyes in the monocular acute CSC patients with PPE.The choroidal capillary layer blood flow density is lower than that of the contralateral and normal eyes.
Purpose. To report the application of 25 MHz B-scan ultrasonography (MHzB) to determine the integrity of the posterior capsule (PC) in posterior polar cataract (PPC). Methods. Patients with whom PPC was clinically diagnosed using slit lamp microscopy who underwent 25 MHzB before phacoemulsification were retrospectively reviewed. The status of the PC was determined by 25 MHzB before phacoemulsification and confirmed during cataract surgery. Results. In total, 21 eyes in 14 clinically diagnosed PPC patients were enrolled in this study. Out of 25 MHzB images, 19 PCs were found to be intact, while 2 showed dehiscence before cataract surgery. During phacoemulsification, 17 PCs were observed to be intact, while 4 PCs showed posterior capsule rupture (PCR). These 4 PCR cases included the above 2 eyes, in which preexisting dehiscence was detected by 25 MHzB. The other 2 PCR cases showed high reflectivity between high echoes in posterior opacities and the PC, indicating synechia between the PPC and PC. Conclusion. This is the first report to show that 25 MHzB can be used to clearly visualize the status of the PC in PPC. These results, in turn, could be used to select the appropriate treatment and to thereby avoid further complications during PPC surgery.
AIM:To compare the results of axial length (AL) biometry in cataract eyes by three methods: immersion B-ultrasound (IB) biometry, immersion A-ultrasound (IA) biometry and optical low coherence reflectometry.METHODS:In this prospective observational study of eyes with cataract AL measurements were performed using immersion ultrasound and optical low coherence reflectometry device. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t-test, and its correlation was evaluated by Pearson coefficient.RESULTS:Eighty eyes of 80 patients (39 men and 41 women) for cataract surgery were included in the study. The values of AL could be got from all 80 eyes by IB and IA, the difference of AL measurements between IA and IB was of no statistical significance (P=0.97); the mean difference in AL measurements was -0.031 mm (P=0.26; 95%CI, -0.09 to 0.02); linear regression showed an excellent correlation (r=0.98, P<0.0001). Forty-five of eighty eyes with results of AL measurements, which can be obtained by three methods; the difference of AL measurements was of no statistical significance (IA vs IB, P=0.18; IA vs Lenstar, P=0.51; IB vs Lenstar, P=0.07); linear regression showed an excellent correlation (IA vs IB, r=0.99; IA vs Lenstar, r=0.96; IB vs Lenstar, r=0.96); Bland-Altman analysis also showed good agreement between the two methods [IA vs IB, 95% limits of agreement (LoA), -0.36 to 0.28 mm; IA vs Lenstar, 95% LoA, -0.65 to 0.69 mm; IB vs Lenstar, 95% LoA, -0.55 to 0.68 mm].CONCLUSION:Measurements with the optical low coherence reflectometry correlated well with IB and IA. In the eyes with serious refractive medium opacity, the measurements of AL could not be achieved or existed deviations when using optical low coherence reflectometry device. Under such circumstances, we should choose IA or IB as the optimization method to obtain measurements, in order to get much more accurate results.
Background The situation of zonule is very important for determining the cataract surgery.Ultrasound biomicroscopy (UBM) is an important method to observe the situation of zonule before cataract surgery.Objective This study was to evaluate the accuracy and clinical significance of observing the zonule of cataract patients by UBM.Methods A series cases-observational study was performed.One hundred and thirty eyes of 130 cataract patients who were to receive extracapsular cataract enucleation were enrolled in Tianjin Eye Hospital from January to June 2015,including 59 eyes with cataract associated with primary angle-closure glaucoma (PACG) and 71 eyes with traumatic cataract.UBM examination was carried out before surgery,and the abnormalities of zonule were recorded and compared between UBM and surgery findings.This study was approved by the Ethic Committee of Tianjin Eye Hospital and informed consent was obtained from all subjects.Results A large space between lens and cilliary was exhibited and the echo of zonule was clear on the UBM image in the eyes with traumatic cataract.The typical anatomic findings of the anterior eye segment were displayed,and lens equator came into contact with cilliary on the UBM image,and the echo of zonule was blurry in the eyes with cataract associated with PACG.The eye number of abnormal zonule was consistent between UBM and surgery findings (Kappa=O.952),and no significant difference in the eye number of abnormal zonule between UBM and surgery findings (P =0.250).In 75 zonule abnormal eyes diagnosed by both UBM and surgery findings,zonule abnormal range could not be compared in 1 eye (1/130,0.77%),and exactly consistent in 8 eyes (8/130,6.15%) between the two methods.The difference of zonule abnormal range between the two methods was 1 clock in 35 eyes (35/130,26.92%),and 2 clock in 27 eyes (27/130,20.77%),3 clock in 4 eyes (4/130,3.08%).In 74 zonule abnormal eyes,the mean difference of zonule abnormal meridian between the two methods was (1.36 ± 1.29) clock,an those in 28 traumatic cataract eyes and 36 cataract with PACG eyes were (1.14±1.10) clock and (1.64-± 1.48) clock,respectively.Conclusions UBM is able to observe zonule accurately,the observation effectiveness of UBM for traumatic cataract is better than that of cataract combined with PACG.These results are of clinical valueable for surgical strategy of cataract and prediction of surgical complications.
The reaction tolerates various functional groups.