Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit’s width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons’ activities and help reveal the potential functional connections in the whole zebrafish’s brain.OCIS codes: (180.2520) Fluorescence microscopy, (110.0110) Imaging systems, (170.3880) Medical and biological imaging, (170.2945) Illumination design, (180.1790) Confocal microscopy     

Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

Background:

Previous studies have indicated that the cognitive deficits in patients with Alzheimer''s disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

Methods:

Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and “small-world” property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz, and 0.11–0.25 Hz).

Results:

At lower-frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz), the global efficiency, the CC and the “small-world” properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11–0.25 Hz), the CpL was much longer, and the “small-world” property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

Conclusions:

This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.     

Pyrolysis Kinetic Properties of Thermal Insulation Waste Extruded Polystyrene by Multiple Thermal Analysis Methods

Extruded polystyrene (XPS) is a thermal insulation material extensively applied in building systems. It has attracted much attention because of outstanding thermal insulation performance, obvious flammability shortcoming and potential energy utilization. To establish the reaction mechanism of XPS’s pyrolysis, thermogravimetric experiments were performed at different heating rates in nitrogen, and multiple methods were employed to analyze the major kinetics of pyrolysis. More accurate kinetic parameters of XPS were estimated by four common model-free methods. Then, three model-fitting methods (including the Coats-Redfern, the iterative procedure and masterplots method) were used to establish the kinetic model. Since the kinetic models established by the above three model-fitting methods were not completely consistent based on different approximations, considering the effect of different approximates on the model, the reaction mechanism was further established by comparing the conversion rate based on the model-fitting methods corresponding to the possible reaction mechanisms. Finally, the accuracy of the above model-fitting methods and Particle Swarm Optimization (PSO) algorithm were compared. Results showed that the reaction function g(α) = (1 − α)⁻¹ − 1 might be the most suitable to characterize the pyrolysis of XPS. The conversion rate calculated by masterplots and PSO methods could provide the best agreement with the experimental data.     

One-step solution synthesis of a two-dimensional semiconducting covalent organometallic nanosheet via the condensation of boronic acid

In this work, a 2D covalent organometallic nanosheet (COMS) was designed and successfully synthesized through the one-step conjunction of a terpyridine–metal–terpyridine (TMT) sandwich coordinate motif with borate ester covalent heterocyclic (B₃O₃) linkage via the condensation of boronic acid. The obtained 2D COMS with a cobalt coordination center (2D COMS-Co) showed promising p-type semiconducting properties.

A 2D covalent organometallic nanosheet (COMS-Co) was synthesized through the one-step conjunction of sandwich coordinate motif with covalent heterocyclic linkage via the condensation of boronic acid, and it showed promising semiconducting properties.

Two-dimensional (2D) metal–organic frameworks (MOFs) obtained by using the strong bonding effects between metal ions and organic molecule species have aroused great interest;^1–8 these include coordination nanosheets, which are a class of 2D materials featuring metal complex motifs.^9–12 Covalent bonds are considered to be an effective way to fabricate covalent organic frameworks (COFs) such as COF-1, which is mainly constructed by a phenyl ring and borate ester to form covalent heterocyclic (B₃O₃) linkage.^13–15 Based on the synergistic effects of metal coordination and covalent interactions, Jiang and co-workers demonstrated the important role of central metals in controlling π-electronic functions through Mpc-COF.¹⁶ Nevertheless, the coordination bond forms spontaneously within the ring of the porphyrin heterocycle and not as the linkage between organic components. In addition, the connections made between metal ions and ligand motifs cannot facilitate the proper tuning of the physicochemical properties of the structure.¹⁷ Combining the covalent and coordinate features may provide an opportunity to design new 2D materials and thus, the synergetic enhancement in many unique properties can be achieved. As far as we know, the fabrication of 2D semiconducting materials that combine the covalent heterocyclic linkage and coordinate linkage has not been reported. Therefore, it is a pressing need to construct a functional 2D organic framework through a one-step synthesis strategy, which would be a more attractive approach.Herein, we first proposed an efficient one-step strategy to synthesize a 2D material by the synergy of covalent and organometallic interactions; it was named as a covalent organometallic nanosheet (2D COMS-M, M = cobalt (Co)). The as-proposed 2D COMS-Co was constructed by linking the borate ester covalent heterocyclic (B₃O₃) structure and terpyridine (tpy) metal coordination motif (TMT) (Fig. 1).Open in a separate windowFig. 1(a) Synthesis route of the semiconducting 2D COMS. (b) Design principles of COMS via the condensation of boronic acid. (c) The calculated cross-sectional view of 2D COMS-Co.In order to explore the extended construction of 2D COMS, the self-condensation ligand 4-phenylborate-2,2′; 6′,2′′-terpyridine (L¹) integrated with CoCl₂ as the Co²⁺ carrier was employed through an anhydrous and oxygen-free hydrothermal reaction at 120 °C under argon, and the typical synthesis process is depicted in Fig. 1a (for details, please see ESI^†). Starting from the condensation reaction of boronic acid (Fig. 1b), H₂O could be generated and played a key role in dissolving CoCl₂ and further releasing Co²⁺ ions (CoCl₂ is practically insoluble in mesitylene and dioxane). This was followed by coordination between the terpyridine motifs and the released Co²⁺ ions to obtain 2D COMS. This novel strategy could achieve crystalline 2D materials by self-controlling the release of Co²⁺ through the one-step condensation reaction of boronic acid. The calculated cross-sectional view of 2D COMS-Co indicates that the thickness of the monolayer 2D COMS-Co is 0.69 nm (Fig. 1c). The dual synergistic connecting effects of covalence and coordination in 2D COMS-Co provided nanosheet-like morphology with significant improvement in the semiconducting performance. The hole mobility of the 2D COMS-Co-based FET device could reach to 5.7 × 10⁻⁵ cm² V⁻¹ s⁻¹ with an ON–OFF ratio of 221, which demonstrated the potential application of 2D COMS-Co in semiconducting devices.The scanning electron microscopy (SEM) image (Fig. 2a) reveals that 2D COMS-Co has a uniform micron-sized nanosheet-like structure. Furthermore, the transmission electron microscopy (TEM) image indicates that the as-synthesized 2D COMS-Co consists of few multi-layers. Fig. 2c shows an enlarged image of the selected area visualized with high-resolution TEM (HRTEM), where the section enclosed by white lines depicts lattice fringes. Moreover, the selected area electron diffraction (SAED, inset of Fig. 2c) image shows a circular ring pattern that reveals the well-defined crystalline structure of 2D COMS-Co; these results are in agreement with our X-ray diffraction data (Fig. S2, ESI^†). Most interestingly, the atomic force microscopy (AFM) image (Fig. 2d) clearly demonstrates that the selected thickness of 2D COMS-Co is 2.07 nm, and the resultant thickness is three times less than the calculated value of 0.69 nm (Fig. 1c), indicating its uniform three-layer stacked structure. The above results collectively provide strong evidence of typical 2D features for COMS-Co. Moreover, the high-angle annular dark-field (HAADF) image and the scanning transmission electron microscopy (STEM) elemental mapping further revealed that the C (red), B (cyan), N (green), O (blue) and Co (pink) elements are homogeneously distributed on the selected area of 2D COMS-Co (Fig. 2e–k). The electronic structure of 2D COMS-Co was further characterized by four-probe scanning tunnel microscopy (STM) (please see details in ESI^†). The high-resolution STM imaging revealed that the 2D COMS-Co flake has a layered flake structure with uniformly distributed hexagonal hole morphology and the resultant holes have a diameter of 4.72 nm (Fig. 2l); this observation is in accordance with the proposed structure of 2D COMS-Co (Fig. S8, ESI^†).Open in a separate windowFig. 2Morphological characterization of 2D COMS-Co. (a) SEM image of powder. (b) TEM image. (c) HRTEM image (d) AFM image. (e) HAADF image. (f–k) STEM elemental mapping. (l) STM image.Due to the covalence and coordination effects, the absorption peak of 2D COMS-Co obtained from the UV-vis measurements (Fig. 3a) is red-shifted in comparison to that for ligand L¹, and the optical band gap is calculated to be 1.85 eV. Furthermore, density functional theory (DFT) calculations revealed that the highest occupied molecular orbital (HOMO) of 2D COMS-Co was dominated by the π orbital of the B₃O₃ linkage and the phenyl ring, whereas the π* orbital of TMT was responsible for the lowest unoccupied molecular orbital (LUMO). Additionally, the calculated electronic band gap of 2D COMS-Co was 1.89 eV, which was in accordance with the optical band gap, confirming the successful synthesis of 2D COMS-Co. Fig. 3b displays the X-ray photoelectron spectroscopy (XPS) spectrum of 2D COMS-Co, in which the appearance of the binding energy peak at 192.2 eV is significantly different from that for L¹ (191.1 eV), which can be ascribed to the –C–B–O₂ structure.^18,19 Compared to the observation for L¹, the N 1s peak for 2D COMS-Co shifted to a higher binding energy value (399.2 eV for COMS-Co and 397.5 eV for L¹). The skewing of the peaks toward higher binding energy was induced by the contribution of N atoms in terpyridine to the metal center. Therefore, the XPS results clearly provide evidence of the existence of both covalent and coordination effects in the as-prepared 2D COMS-Co. The Fourier transform infrared (FT-IR) spectra in Fig. 3c show that the –B(OH)₂ bands (around 3500 cm⁻¹) of the ligand L¹ are significantly attenuated compared to that observed for 2D COMS-Co. In addition, the B–O stretching vibrations at 1351 cm⁻¹ can be observed for 2D COMS-Co but not for L¹.^13,20–22 Thus, the above results show that the expected B₃O₃ rings for 2D COMS-Co have indeed been formed. Notably, the nitrogen adsorption–desorption isotherms reveal that the Brunauer–Emmett–Teller (BET) specific surface area of 2D COMS-Co is as high as 598 m² g⁻¹ (Fig. 3d); it surpasses those of other layered materials, including the reported graphene oxide paper (10 m² g⁻¹), clays (10 to 100 m² g⁻¹), and pillared clays (50 to 300 m² g⁻¹), and is in the range of the values of the most porous zeolites and many porous carbons.^13,23 This drastic enhancement can be assigned to the uniform porous structure of the as-synthesized 2D COMS-Co.Open in a separate windowFig. 3(a) UV-vis spectra of L¹ and 2D COMS-Co (left), electron distribution on HOMO/LUMO and the orbital energy gap (right). (b) XPS B 1s and N 1s spectra of L¹ and 2D COMS-Co. (c) FT-IR spectra of L¹ and 2D COMS-Co. (d) N₂ adsorption and desorption isotherms of 2D COMS-Co (inset: stacking porous view).The above results show that the 2D COMS-Co units arranged in periodic strips can provide conducting pathways for charge carrier transport through TMT and central cobalt ions. 2D COMS-Co was employed to function as the active semiconducting channel in a field-effect transistor (FET) device. As shown in Fig. 4a, the individual 2D COMS-Co sample is deposited on an Si wafer as the semiconducting layer to construct the FET device. The 2D COMS-Co-based FET device delivered hole mobility of 5.7 × 10⁻⁵ cm² V⁻¹ S⁻¹ and an ON/OFF ratio of 221, which were comparable with those of previously reported 2D MOFs (Table S1^†). Therefore, these results collectively demonstrate the potential application of 2D COMS-Co in semiconducting devices.Open in a separate windowFig. 4(a) Schematic of the FET device employing 2D COMS-Co as the semiconducting layer. (b) Transfer curve of the 2D COMS-Co-based FET device with the inset showing an optical and model diagram of the device; V_G is the gate-source voltage and I_D is the drain current.In summary, a novel two-dimensional covalent organometallic nanosheet (COMS) was designed and successfully synthesized through the strategy of one-step conjunction of a TMT sandwich coordinate motif with B₃O₃ linkage. This facile strategy could achieve crystalline 2D COMS-Co by self-controlling the release of Co²⁺ through a one-step condensation reaction of boronic acid. The systematic characterization demonstrated the successful preparation of porous and crystalline 2D COMS-Co. Particularly, the as-prepared 2D COMS-Co-based FET device presented hole mobility of 5.7 × 10⁻⁵ cm² V⁻¹ S⁻¹ and an ON/OFF ratio of 221, which demonstrated the potential application of 2D COMS-Co in semiconducting devices. Therefore, we envision that this work will open a new avenue for the synthesis of two-dimensional semiconducting covalent organometallic materials by using covalence and coordination dual synergistic connection effects via a one-step facile strategy.     

One-step synthesis of red-emitting carbon dots via a solvothermal method and its application in the detection of methylene blue

The synthesis of carbon dots (CDs) with long wavelengths, particularly the red-emitting ones, has always been the focus of researchers, and a carbon source is critical in this process. In this study, we report the synthesis of red-emitting CDs (CD-tetra) via a one-step solvothermal method with 1,2,4,5-benzenetetramine tetrahydrochloride as a novel carbon source and ethanol as a solvent, and the quantum yield (QY) of CDs is as high as 30.2%. Middle chromatography isolated gel (MCI Gel) column was used to obtain R-CDs, O-CDs and Y-CDs with emission wavelengths at 619, 608 and 554 nm, respectively. It was discovered that these CDs exhibited great differences in their particle sizes and elemental compositions. Moreover, the fluorescence of the CD-tetra could be efficiently quenched using methylene blue (MB). Under optimal conditions, a linear relationship between the decreased fluorescence intensity of the CD-tetra and the concentration of MB was established in the range of 0.05–9.5 μM. The limit of detection (LOD) is 10 nM, suggesting a promising assay for the detection of MB.

Red-emitting CDs was synthesized via a one-step solvothermal method with 1,2,4,5-benzenetetramine tetrahydrochloride as a novel carbon source and ethanol as a solvent. The luminescence mechanism of CDs was studied by MCI gel column chromatography.     

The latent factors of depression from the short forms of the CES-D are consistent,reliable and valid in community-living older adults

BackgroundDepression is an important public health outcome in the older adult population. It is associated with declining physical and psychological well-being and increasing healthcare utilisation. The Center for Epidemiological Studies Depression Scale (CES-D) although widely accepted as a screening tool for depressive symptoms in older adults, can be long and exhaustive as part of a comprehensive geriatric assessment.AimWe investigated the consistency, reliability and validity of the original and three short formats of the CES-D.MethodsSix thousand six hundred and thirty-seven community-living adults, aged ≥ 50 years from The Irish Longitudinal Study on Ageing (TILDA), completed the 20-item CES-D. Confirmatory factor analysis determined the factor structures of the 20-, 10- and two 8-item formats of the CES-D. Latent factors from each format were validated against disability and perceived stress, particularly the Positive Affect factor. Analysis was also performed in a subset aged 65+ years.ResultsAll formats of the CES-D displayed good internally consistency (0.87–0.72) and good model fit for the expected four- and three-factor structures of the CES-D. Latent factors from all formats were representative of each other and the Positive Affect factor was negatively correlated with disability and perceived stress on all CES-D formats.ConclusionShort forms of the CES-D are consistent, reliable and valid for use in the older adult population (50+ or 65+ years), where avoiding long assessments and response fatigue is warranted. These formats may be used to measure Positive Affect, an important construct related to physical health, resilience and psychological well-being in later life.     

分布式家庭医生服务系统与区块链电子病历

对比传统集中式系统、分布式系统优缺点,指出分布式架构可解决传统架构存在的模块之间耦合度高、开发效率低等问题,设计构建分布式家庭医生服务系统,包括系统功能需求、体系架构、功能架构、分布式服务框架、服务调用流程等,同时在该系统中开发区块链电子病历,该系统及电子病历均通过测试。     

补肾壮腰膏联合补肾祛瘀针法治疗腰椎间盘突出症急性发作的疗效观察

目的 研究补肾壮腰膏联合补肾祛瘀针法在腰椎间盘突出症急性发作治疗中的临床疗效。 方法 研究纳入2016年10月—2018年12月期间湖北省中医院收治的因急性发作入院治疗的腰椎间盘突出症患者120例,采用随机数字表法分为观察组和对照组各60例,其中,对照组行补肾祛瘀针法治疗,观察组在对照组基础上加用补肾壮腰膏口服,均连续治疗2周后观察疗效,比较治疗前后的JOA下腰痛评分、ODI评分及血清中炎性因子和疼痛相关介质水平的变化。 结果 观察组患者治疗后的总有效率为88.3%,显著优于对照组的75.0%,比较差异有统计学意义(χ2=5.604,P<0.05)。2组患者治疗前的JOA下腰痛评分、ODI评分以及IL-1β、IL-6、IL-10、TNF-α炎性因子水平和PGE2、5-HT、BK、NPY疼痛介质水平比较,差异均无统计学意义(均P>0.05),具有可比性;与治疗前比较,2组患者治疗后的上述指标结果均有显著改善(均P<0.05);与对照组比较,观察组患者治疗后的上述指标结果亦可见显著改善(均P<0.05)。 结论 补肾壮腰膏联合补肾祛瘀针法治疗腰椎间盘突出症急性发作疗效显著,能够明显改善患者的临床症状,并降低炎症反应和疼痛介质水平。      

新型人用狂犬病疫苗研究进展

虽然狂犬病可通过接种狂犬病疫苗来预防,但全球每年仍有超过55 000人因狂犬病死亡。采用现行狂犬病疫苗的多剂接种方案,暴露前疫苗接种对大多数国家来说不具有成本效益,因此有必要开发新型狂犬病疫苗。理想的狂犬病疫苗应与现行的多剂疫苗同样安全,而且单剂接种后就能达到保护性免疫。此综述讨论了处于临床前试验和正在进行临床试验的新型狂犬病疫苗,及其替代现有狂犬病疫苗的潜力。