Isotropic multi-scale neuronal reconstruction from high-ratio expansion microscopy with contrastive unsupervised deep generative models.

BACKGROUND AND OBJECTIVE: Current methods for imaging reconstruction from high-ratio expansion microscopy (ExM) data are limited by anisotropic optical resolution and the requirement for extensive manual annotation, creating a significant bottleneck in the analysis of complex neuronal structures. METHODS: We devised an innovative approach called the IsoGAN model, which utilizes a contrastive unsupervised generative adversarial network to sidestep these constraints. This model leverages multi-scale and isotropic neuron/protein/blood vessel morphology data to generate high-fidelity 3D representations of these structures, eliminating the need for rigorous manual annotation and supervision. The IsoGAN model introduces simplified structures with idealized morphologies as shape priors to ensure high consistency in the generated neuronal profiles across all points in space and scalability for arbitrarily large volumes. RESULTS: The efficacy of the IsoGAN model in accurately reconstructing complex neuronal structures was quantitatively assessed by examining the consistency between the axial and lateral views and identifying a reduction in erroneous imaging artifacts. The IsoGAN model accurately reconstructed complex neuronal structures, as evidenced by the consistency between the axial and lateral views and a reduction in erroneous imaging artifacts, and can be further applied to various biological samples. CONCLUSION: With its ability to generate detailed 3D neurons/proteins/blood vessel structures using significantly fewer axial view images, IsoGAN can streamline the process of imaging reconstruction while maintaining the necessary detail, offering a transformative solution to the existing limitations in high-throughput morphology analysis across different structures.

Construction and optimization of a novel plasma membrane model for membrane affinity assay based on polydiacetylene vesicles / 药学学报

Most drugs need to interact with cell membrane to reach the biological target, so that membrane affinity assay is an important early screening step in drug discovery. However, at present, the traditional oil-water distribution method is still used, a new, simple and accurate method for membrane affinity assay is urgently needed. In this study, according to the colorimetric principle, a new assay model based on polydiacetylene vesicles was optimized through a series of experiments including different concentrations of vesicle solution, temperature, or pH reaction environment. On this basis, tetracaine hydrochloride, 2-methylimidazole and histamine were used as model drugs to measure the membrane affinity constants and verify the between-batch precision of the optimized assay model (relative standard deviation less than 5%). In addition, polydiacetylene vesicles were stable for up to 180 days, demonstrating the potential application of the assay model. This strategy is simple, stable, reliable, with high reproducibility, low cost and easy to promote, which provided a new tool and a new direction for the high-throughput assay of membrane affinity.

Nucleic acid drug delivery strategies without the lysosomal pathway / 中国药科大学学报

@#By regulating gene expression, nucleic acid drugs functioning in the cytoplasm or nucleus are of great significance in the treatment of acquired or inherited diseases and vaccine development.A variety of nucleic acid delivery vectors currently developed are suffering from low transfection efficiency due to endosome/lysosome entrapment.This paper introduces and summarizes the nucleic acid delivery strategies that bypass the endosomal/lysosomal pathway, including membrane translocation, membrane fusion, receptor/transporter-mediated non-endocytic uptake and caveolae-mediated endocytosis, and discusses the problems and challenges facing such strategies, aiming to facilitate the development of intracellular delivery of nucleic acid drugs bypassing lysosomal pathway.

QCW surface-pumped cryogenically cooled single-slab laser with 1 kW level at 946 nm.

We present a kilowatt-level quasi-continuous-wave (QCW) cryogenically cooled 946-nm slab laser oscillator for the first time, to the best of our knowledge. The laser system is based on a double-face-pumped large-size single-slab Nd:YAG design, delivering a record-high average power of 1.06 kW without additional amplification. This laser oscillator operates at repetition rate of 400 Hz with a pulse duration of 175 µs, resulting in a single pulse energy of 2.65 J. To the best of our knowledge, these results represent the highest output power and pulse energy for any all-solid-state 946-nm laser ever reported to date. Our scheme paves a new path for the development of the compact high-power solid-state 946-nm laser.

Primary aberration optimization for double-plane symmetric beam shaping systems using a pair of curved reference surfaces.

The geometric aberration of centered refracting double-plane symmetric optical systems (DPSOS) is investigated. For DPSOS with different defocus values in the tangential plane and the sagittal plane (astigmatic wavefront), a pair of curved reference surfaces which vanishes the quadratic terms of the optical path difference (OPD) between a general ray and a reference ray are deduced. With the curved reference surfaces, the primary (fourth-order) wave aberration function for DPSOS is calculated and analyzed, which can be used for beam shaping designs with astigmatic input wavefront, such as slab lasers and semiconductor lasers. Further, the proposed curved reference surfaces can be applied to analyze the aberrations of general DPSOS.

Compact integrated aberration-compensating module for a 9 kW Nd:YAG slab laser based on an off-axis stable-unstable resonator.

An integrated aberration-compensating module (IACM), consisting mainly of an adjustable slab-aberration compensator, a one-dimensional Shack-Hartmann wavefront sensor, and a data processor, which meet the urgent requirements of correcting the specific wavefront aberrations of a slab laser based on an off-axis stable-unstable resonator, is designed and experimentally demonstrated. Benefits include compactness, robustness, simplicity, automation, and cost-effectiveness. The particular wavefront aberrations of the 9 kW level quasi-continuous-wave Nd:YAG slab laser, which have characteristics of asymmetry, large amplitude and gradient, high spatial frequency, and low temporal frequency, were measured and theoretically analyzed. In the experiment, the wavefront aberrations of the slab laser were corrected by the IACM. At the average output power of 9 kW, the diffraction-limited factor ß was improved from 20.3 times diffraction limit (DL) to 3.6 times DL. The peak-to-valley and root-mean-square values of aberrations were reduced from 9.6 to 0.85 µm and from 2.86 to 0.18 µm within five iterations of the IACM, respectively. Moreover, The IACM is capable of maintaining the compensating surface figure after power-off.

Anti-inflammatory sesquiterpene dimers and diterpenes from the aerial part of Inula japonica.

Phytochemical investigation on the 95% alcohol extract of the aerial part of Inula japonica led to the isolation of three new compounds, inulanolides F-G (1-2) and 17α-carboxaldehyde-ent-kaur-18-oic acid (3), together with four known compounds (4-7). The structures of new compounds were elucidated by using spectroscopic data. Most of the isolated compounds showed significant anti-inflammatory activities.

Mild Chronic Colitis Triggers Parkinsonism in LRRK2 Mutant Mice Through Activating TNF-α Pathway.

BACKGROUND: Leucine-rich repeat kinase 2 (LRRK2) is a common risk gene for Parkinson's disease (PD) and inflammatory bowel disorders. However, the penetrance of the most prevalent LRRK2 mutation, G2019S, is <50%. Factors other than genetic mutations are needed in PD process. OBJECTIVES: To examine whether and how gut inflammation may act as an environmental trigger to neurodegeneration in PD. METHODS: A mild and chronic dextran sodium sulfate (DSS)-induced colitis mice model harboring LRRK2 G2019S mutation was established. The colitis severity, immune responses, locomotor function, dopaminergic neuron, and microglia integrity were compared between littermate controls, transgenic LRRK2 wild type (WT), and LRRK2 G2019S mice. RESULTS: The LRRK2 G2019S mice are more vulnerable to DSS-induced colitis than littermate controls or LRRK2 WT animals with increased intestinal expressions of pattern-recognition receptors, including toll-like receptors (TLRs), nuclear factor (NF)-κB activation, and pro-inflammatory cytokines secretion, especially tumor necrosis factor (TNF)-α. Notably, the colonic expression of α-synuclein was significantly increased in LRRK2 G2019S colitis mice. We subsequently observed more aggravated locomotor defect, microglia activation, and dopaminergic neuron loss in LRRK2 G2019S colitis mice than control animals. Treatment with anti-TNF-α monoclonal antibody, adalimumab, abrogated both gut and neuroinflammation, mitigated neurodegeneration, and improved locomotor function in LRRK2 G2019S colitis mice. Finally, we validated increased colonic expressions of LRRK2, TLRs, and NF-κB pathway proteins and elevated plasma TNF-α level in PD patients compared to controls, especially in those with LRRK2 risk variants. CONCLUSIONS: Our findings demonstrate that chronic colitis promotes parkinsonism in genetically susceptible mice and TNF-α plays a detrimental role in the gut-brain axis of PD. © 2021 International Parkinson and Movement Disorder Society.

Simplified analytical method for an anamorphic refractive shaping system of laser beams with a large aspect ratio.

For reshaping aperture size and correcting low-order aberration of laser beams with large aspect ratios, a simplified analytical method is proposed to design an anamorphic refractive shaping system, which is composed of double-plane symmetric lenses. The simplified method enables performing a global study of aberrations via calculating the analytical primary wave aberration function under paraxial approximation. The aberration balance is analyzed with a three-lens laser collimating system and a compact four-lens laser expanding system. Lens bending and conic surfaces are introduced to decrease ray errors. Through the simplified analytical method, anamorphic refractive shaping systems for laser beams with large aspect ratios can be adequately analyzed and conveniently designed.

Peripapillary changes after vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the peripapillary changes after vitrectomy and silicone oil (SO) tamponade in eyes with rhegmatogenous retinal detachment (RRD). METHODS: In this study, 25-gauge vitrectomy with SO tamponade was performed in 22 eyes with RRD. The radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer thickness (RNFLT) were assessed by optical coherence tomography angiography at 2, 4, 8, and 12 weeks postoperatively. The values of healthy fellow eyes were used as controls. RESULTS: The global RPC VDs were significantly lower in the eyes with RRD than in fellow healthy eyes at 2 weeks (P < 0.001), and increased at 4 weeks, then decreased over time after surgery (F = 1.046, P = 0.377). The RPC VDs in the superior-hemifield were lower than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.844, P = 0.010). The global RNFLTs decreased gradually after vitrectomy in the eyes with RRD (F = 1.312, P = 0.276). The RNFLTs in the superior-hemifield were thinner than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.222, P = 0.037). The global, superior, and inferior RNFLTs were correlated with corresponding RPC VDs in the eyes with RRD at all time-points postoperatively (P < 0.05). CONCLUSION: RRD resulted in the decrease of RPC VDs. The RPC VDs recovered in the early postoperative period but were still lower than the normal level. Long-term application of SO tamponade resulted in the reduction of peripapillary VDs secondary to loss of RNFLTs.

Evaluation of macular vessel density changes after vitrectomy with silicone oil tamponade in patients with rhegmatogenous retinal detachment.

AIM: To evaluate macular microvasculature changes in eyes after pars plana vitrectomy (PPV) and intraocular silicone oil (SO) tamponade for macula-off rhegmatogenous retinal detachment (RRD) using optical coherence tomography angiography (OCTA). METHODS: Totally 19 eyes (19 patients) with macula-off RRD who underwent PPV and intraocular SO tamponade were retrospectively reviewed. The parafoveal superficial capillary plexus (SCP) vessel density (VD), deep capillary plexus (DCP) VD, choriocapillaris plexus (CCP) VD, and foveal macular thickness were evaluated using OCTA throughout 16wk postoperatively. The values of healthy fellow eyes were used as control. RESULTS: The parafoveal SCP, DCP, and CCP VDs were significant increased over time in RRD eyes during the 12wk postoperatively, then decreased at 16wk postoperatively (all P<0.01). The ratios of RRD eyes and fellow healthy eyes (r/f ratios) of the SCP and DCP VDs were lower than those of the CCP VD postoperatively (all P<0.05). There were not significant differences in the r/f ratios between SCP and DCP VDs postoperatively (all P>0.05). CONCLUSION: The parafoveal SCP, DCP, and CCP VDs gradually recover over time after PPV surgery with SO tamponade. Long-time SO tamponade might decrease postoperative macular VDs. Compared to parafoveal CCP VD, the parafoveal SCP and DCP VDs were more vulnerable in RRD eyes postoperatively.

Application Advantages of Nanoemulsion in Field of Traditional Chinese Medicine Preparation：A Review / 中国实验方剂学杂志

As a new technology with unique drug delivery advantages， nanoemulsion has been widely used in the field of traditional Chinese medicine （TCM） preparations. By searching， classifying and sorting out the literature reports at home and abroad in recent years， this paper systematically expounded the application advantages and production mechanism of nanoemulsion in delivering effective components of TCM from three aspects of improving oral bioavailability， enhancing targeting effect and delaying drug release. The current formulation optimization strategies， preparation processes and quality evaluation indicators commonly used in TCM nanoemulsion were summarized. Based on the research status of TCM nanoemulsion with different active components， the common problems and possible solutions in the development of TCM nanoemulsion were discussed， and the future research hotspots and directions of TCM nanoemulsion were prospected. This article clarifies the feasibility of nanoemulsion for enriching the selection of TCM dosage forms， which can provide reference for the subsequent rational design and improvement of TCM preparations. At the same time， it is revealed that the research focus of TCM nanoemulsion in the future lies in the integrated research of TCM compounds， and shows a trend of multi-disciplinary joint and targeted research.

Drug target discovery by magnetic nanoparticles coupled mass spectrometry / 药物分析学报

Drug target discovery is the basis of drug screening.It elucidates the cause of disease and the mechanism of drug action,which is the essential of drug innovation.Target discovery performed in biological sys-tems is complicated as proteins are in low abundance and endogenous compounds may interfere with drug binding.Therefore,methods to track drug-target interactions in biological matrices are urgently required.In this work,a Fe3O4 nanoparticle-based approach was developed for drug-target screening in biofluids.A known ligand-protein complex was selected as a principle-to-proof example to validate the feasibility.After incubation in cell lysates,ligand-modified Fe3O4 nanoparticles bound to the target protein and formed complexes that were separated from the lysates by a magnet for further analysis.The large surface-to-volume ratio of the nanoparticles provides more active sites for the modification of chemical drugs.It enhances the opportunity for ligand-protein interactions,which is beneficial for capturing target proteins,especially for those with low abundance.Additionally,a one-step magnetic separation simplifies the pre-processing of ligand-protein complexes,so it effectively reduces the endogenous interference.Therefore,the present nanoparticle-based approach has the potential to be used for drug target screening in biological systems.

Void-free bonding for a large slab laser crystal.

A void-free bonding technique was demonstrated for a large slab Nd: YAG crystal with a bonding surface dimension of ∼160mm×70mm. By using the novel fluxless oxide layer removal technology, the indium-oxide barrier problem was resolved. With the help of electrochemical-polished indium solder and a plasma-cleaned heat sink, the solderability of the indium was enhanced; in particular, the contact angle of the solder was improved from 51° to 31°. With the largest-bonding-size slab, a single-slab laser created a maximum output power of 7.3 kW under an absorbed pump power of 12.8 kW, corresponding to an optical to optical efficiency of 57% and a slope conversion of 67.8%. By detecting the wavefront of the interferometer before and after bonding, the RMS of wavefront was 0.192λ and 0.434λ (λ=633nm), respectively. To the best of our knowledge, this is the largest void-free bonding size for a laser slab and the highest output power achieved from a single-slab crystal laser oscillator.

Recent advances of metal-organic frameworks applied in biomedicine / 药学学报

Metal-organic frameworks (MOFs) are porous crystalline polymers constructed from the coordination reaction between organic ligands and metal ions. Due to their advantages: adjustable periodic pore structure, large specific surface area and easy functional modification, etc., MOFs have been widely used in the fields of gas storage/separation, catalysis, sensing, biological imaging and drug delivery. In recent years, MOFs have shown great potential in disease diagnosis and treatment. This review summarizes the application of MOFs in the fields of bio-sensing, cell imaging, in vivo imaging, drug delivery, etc., discusses the problems and corresponding solutions in the application of MOFs for biomedicine. We hope this review can provide reference for the designing new methods for disease diagnosis and treatment.

Research advances of glutamine metabolism-related targets in tumor treatment / 药学学报

Metabolic reprogramming is an important feature of tumor cell metabolism. Glutamine, as a conditionally essential amino acid, provides material and energy for cell growth and maintains the redox homeostasis of tumor cells. This article reviews the role of glutamine in tumorigenesis, development and metastasis, discusses the relationship between glutamine and key biomacromolecules, and provides ideas for finding new targets in cancer therapy.

Factors influencing demand for emergency education for college students in Liaoning Province / 中国学校卫生

Objective@#To understand demand for emergency education among college students and to analyze the influencing factors, to provide the evidence for college to make prevention and controlling measures.@*Methods@#A survey was conducted among college students who were selected by stratified random sampling from 4 colleges in Liaoning Province, and data were analyzed using general descriptive analysis, chi-square test and multivariate Logistic regression analysis.@*Results@#There were 90.7% of college students who had urgent needs for emergency education. Students who were female(93.9%), seniors(94.4%), learning in medical colleges(97.6%), having mothers with higher education levels(92.6%), and living in urban areas(94.4%) had higher educational needs. Multivariate analysis showed that gender (OR=5.00), school category (OR=3.87), emergency attitude (OR=8.02), active learning behavior (OR=3.91), emergency knowledge self-assessment (OR=6.64) were influencing factors(P<0.05).@*Conclusion@#The emergency knowledge and preparation of college students were insufficient and emergency education was needed. The government and schools should strengthen their attention and input, develop more effective ways to disseminate emergency knowledge among students so as to improve their response ability.

Preparation and applications of gold nanoclusters with precise atom number / 药学学报

Gold nanoclusters (AuNCs) are gold atom aggregates less than 2 nm (excluding the ligand shell) or 150 atoms. It has been widely studied due to its small size effect, fluorescence property, and catalytic activity. In this review, research progress in the preparation of gold nanoclusters containing accurate atom numbers using biomolecules and chemically synthesized molecules as ligands have been summarized. The factors that affect the preparation of gold nanoclusters have been discussed. The applications of AuNCs having accurate atomic numbers in the fields of analyte assay, catalysis, bioimaging, and drug delivery have been introduced. This review provides references to the further researches on the preparation technology and biomedical applications of AuNCs.

Interchangeability and reliability of macular perfusion parameter measurements using optical coherence tomography angiography.

AIM: The aim of the study was to investigate the interchangeability and reliability of macular perfusion measurements using optical coherence tomography angiography. METHODS: A prospective cross-sectional observational study. Healthy adult Chinese subjects were recruited. Macular perfusion parameters were automatically analysed by software included in a spectral-domain optical coherence tomography system. The vessel density (VD) of the whole, parafovea, superior-hemi, inferior-hemi, fovea, temporal, superior, nasal and inferior quadrants as well as the foveal avascular zone (FAZ) and choroidal capillary VD (CCVD) were quantified. RESULTS: A total of 51 eyes in 27 subjects were included (8 men and 19 women, mean age 24±4 years). Significant differences in VD of all quadrants (all p<0.001) was detected between the 3×3 mm and 6×6 mm macular scan size. The biggest difference of VD between the two scan size was 5.14±4.03, which was not clinically meaningful. No statistically significant differences were found in FAZ or CCVD between the two different scan sizes. The mean intraclass correlation coefficient (ICC) between two measurements from the inter-rater of 20 eyes was from 0.560 to 0.893 for VD and 0.845 for FAZ. The mean ICC between two measurements from the intrarater of 20 eyes was from 0.497 to 0.870 for VD and 0.780 for FAZ. CONCLUSIONS: FAZ and CCVD are interchangeable between the 3×3 mm and 6×6 mm macular scan sizes. The VD differences between the two different scan sizes are not clinically meaningful. The macular perfusion parameters presented good but not perfect reliability, which should be acknowledged in clinical practice.