Effects of Starve and Shelter Availability on the Group Behavior of Two Freshwater Fish Species (Chindongo demasoni and Spinibarbus sinensis).

In complex environments, fish often suffer from reduced physiological functioning due to starvation, which may have a significant effect on their behavioral adaptive strategies to predator attacks. We selected qingbo (Spinibarbus sinensis, which prefers flowing water habitats) and demasone cichlid (Chindongo demasoni, which prefers still water habitats), to investigate the differences in group distribution and dynamics between the two species when faced with a simulated predation attack under different trophic states (fasted for 2 weeks or fed). We chose to conduct our experiments in a six-arm maze that included a central area and six arms of equal length and width and to obtain evidence of how the fish used the various areas of the maze to respond to simulated predation attacks. We found that the two fish species differed in their responses to simulated predation attacks under different trophic states. The group structure of the two species was relatively stable, and the effect of fasting on the qingbo group was not significant, whereas the demasone cichlid group was more susceptible to the effects of fasting, shelter and a simulated predation attack. In an environment with shelter, both species had the same anti-predator strategy and tended to enter the shelter arm to hide after encountering a simulated predation attack. However, differences in the anti-predator strategies of the two species emerged in the no-shelter environment, with the qingbo tending to enter the arm to hide, whereas the demasone cichlid group chose to enter the central area to congregate, and this phenomenon was more pronounced in the fasted group. In conclusion, our research shows that even group-stable fish may shift their anti-predation strategies (i.e., entering a shelter to hide shifts to aggregating in situ into a shoal) when starved and that the worse the swimming ability of the fish, the more affected they are by starvation.

Oxygen levels differentially attenuate the structure and diversity of microbial communities in the oceanic oxygen minimal zones.

Global change mediated shifts in ocean temperature and circulation patterns, compounded by human activities, are leading to the expansion of marine oxygen minimum zones (OMZs) with concomitant alterations in nutrient and climate-active trace gas cycling. While many studies have reported distinct bacterial communities within OMZs, much of this research compares across depths rather with oxygen status and does not include eukayrotic microbes. Here, we investigated the Bay of Bengal (BoB) OMZ, where low oxygen conditions are persistent, but trace levels of oxygen remain (< 20 µM from 200 to 500 m). As other environmental variables are similar between OMZ and non-OMZ (NOZ) stations, we compared the abundance, diversity, and community composition of several microbial groups (bacterioplankton, Labyrinthulomycetes, and fungi) across oxygen levels. While prokaryote abundance decreased with depth, no significant differences existed across oxygen groups. In contrast, Labyrinthulomycetes abundance was significantly higher in non-OMZ stations but did not change significantly with depth, while fungal abundance was patchy without clear depth or oxygen-related trends. Bacterial and fungal diversity was lower in OMZ stations at 500 m, while Labyrinthulomycetes diversity only showed a depth-related profile, decreasing below the euphotic zone. Surprisingly, previously reported OMZ-associated bacterial taxa were not significantly more abundant at OMZ stations. Furthermore, compared to the bacterioplankton, fewer Labyrinthulomycetes and fungi taxa showed responses to oxygen status. Thus, this research identifies stronger oxygen-level linkages within the bacterioplankton than in the examined microeukaryotes.

A Novel Hand-held Multi-color Magnetic Particle Imaging Device based on Rapid Frequency Conversion.

OBJECTIVE: Multi-color Magnetic Particle Imaging (MPI) technology offers high sensitivity and non-invasive imaging capabilities. It can simultaneously image multiple superparamagnetic iron oxide nanoparticles (SPIOs), facilitating more precise detection of multiple molecular markers in vivo. However, the fixed drive frequency of existing hand-held MPI devices makes it difficult to fully match the nonlinear magnetic response of different SPIOs, affecting the spatial resolution and quantitative accuracy of multi-color imaging. METHODS: We designed a novel rapid frequency conversion based hand-held multi-color magnetic particle imaging (RFC-MPI) device. This device adjusts the drive frequency based on the nonlinear magnetic response of SPIOs at different frequencies, effectively expanding the system matrix information and thereby improving spatial resolution and multi-color imaging capabilities simultaneously. RESULTS: The device achieved a spatial resolution of 2 mm and an imaging speed of 1 frame/s. The scanning depth is 8 mm. It was used to scan a 22 cm x 22 cm area of a human-shaped phantom, verifying its potential for scanning humans. The ability of the device to identify and quantify SPIOs was validated using mice breast tumors. The quantitative accuracy during simultaneous imaging was determined to be 96.58%. CONCLUSION: Due to its innovative structural design and rapid frequency conversion method, the RFC-MPI device exhibits excellent in vivo imaging performance. Both simulation and phantom experiments have verified the effectiveness of the proposed method. SIGNIFICANCE: The hand-held RFC-MPI device can effectively improve the spatial resolution and quantitative accuracy of multi-color MPI, laying the foundation for future clinical applications.

Selective directional liquid transport on shoot surfaces of Crassula muscosa.

Directional liquid transport has been widely observed in various species including cacti, spiders, lizards, the pitcher plant Nepenthes alata, and Araucaria leaves. However, in all these examples the liquid transport for a specific liquid is completely restricted in a fixed direction. We demonstrate that Crassula muscosa shoot surfaces have the ability to transport a specific liquid unidirectionally in either direction. This is accomplished through the presence of asymmetric reentrant leaves with varying reentrant angles, which yields the variation in liquid meniscus heterogeneity. These findings enable engineered biomimetic structures capable of selective directional liquid transport, with functions such as intelligent flow direction switching, liquid distribution, and mixing.

Targeted gene delivery systems for T-cell engineering.

T lymphocytes are indispensable for the host systems of defense against pathogens, tumors, and environmental threats. The therapeutic potential of harnessing the cytotoxic properties of T lymphocytes for antigen-specific cell elimination is both evident and efficacious. Genetically engineered T-cells, such as those employed in CAR-T and TCR-T cell therapies, have demonstrated significant clinical benefits in treating cancer and autoimmune disorders. However, the current landscape of T-cell genetic engineering is dominated by strategies that necessitate in vitro T-cell isolation and modification, which introduce complexity and prolong the development timeline of T-cell based immunotherapies. This review explores the complexities of gene delivery systems designed for T cells, covering both viral and nonviral vectors. Viral vectors are known for their high transduction efficiency, yet they face significant limitations, such as potential immunogenicity and the complexities involved in large-scale production. Nonviral vectors, conversely, offer a safer profile and the potential for scalable manufacturing, yet they often struggle with lower transduction efficiency. The pursuit of gene delivery systems that can achieve targeted gene transfer to T cell without the need for isolation represents a significant advancement in the field. This review assesses the design principles and current research progress of such systems, highlighting the potential for in vivo gene modification therapies that could revolutionize T-cell based treatments. By providing a comprehensive analysis of these systems, we aim to contribute valuable insights into the future development of T-cell immunotherapy.

Ca2+-sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress.

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that low concentrations of GPN rupture a small fraction of lysosomes, but surprisingly trigger Ca2+ release from nearly all. Chelating cytoplasmic Ca2+ makes lysosomes more sensitive to GPN-induced rupture, suggesting a role for Ca2+ in lysosomal membrane resilience. GPN-elicited Ca2+ release causes the Ca2+-sensor Apoptosis Linked Gene-2 (ALG-2), along with Endosomal Sorting Complex Required for Transport (ESCRT) proteins it interacts with, to redistribute onto lysosomes. Functionally, ALG-2, but not its ESCRT binding-disabled ΔGF122 splice variant, increases lysosomal resilience to osmotic stress. Importantly, elevating juxta-lysosomal Ca2+ without membrane damage by activating TRPML1 also recruits ALG-2 and ESCRTs, protecting lysosomes from subsequent osmotic rupture. These findings reveal that Ca2+, through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress.

Space-Specific Mixing Excitation for High-SNR Spatial Encoding in Magnetic Particle Imaging.

OBJECTIVE: Magnetic Particle Imaging (MPI) is a radiation-free tracer-based imaging technology that visualizes the spatial distribution of superparamagnetic iron oxide nanoparticles. Conventional spatial encoding methods in MPI rely on a gradient magnetic field with a constant gradient strength to generate a field-free point or line for spatial scanning. However, increasing the gradient strength can enhance theoretical spatial resolution but also lead to a decrease in the Signal-to-Noise Ratio (SNR) and sensitivity of the imaging system. This poses a technical challenge in balancing spatial resolution and sensitivity, necessitating intricate hardware design. METHODS: To address this, we present a Space-Specific Mixing Excitation (SSME) technique for achieving high-SNR spatial encoding in MPI. By utilizing a dual-frequency excitation magnetic field with a non-homogeneous field strength, magnetic particles at each position generate unique intermodulation responses. By performing multi-channel acquisitions across the entire field of view, high SNR MPI signals can be acquired. When combined with reconstruction techniques based on system matrix, multi-dimensional SSME-MPI can be achieved. RESULTS: The effectiveness of the proposed method was validated through phantom and in vivo imaging experiments. The results demonstrate significant improvements in sensitivity (3.6-fold improvement) and spatial resolution (better than 1 mm) without any hardware modifications. CONCLUSION: These findings demonstrate the capability of SSME to enhance both the spatial resolution and sensitivity of MPI. SIGNIFICANCE: This method provides a solution to the ongoing challenge of balancing spatial resolution and sensitivity in MPI, potentially facilitating the implementation of MPI in a wider range of medical applications.

The predictive value of serum F-actin on the severity and early neurological deterioration of acute ischemic stroke: Predictive value of F-actin in stroke.

BACKGROUND: F-actin is involved in the progression of ischemic stroke and is associated with the disruption of the blood-brain barrier. In this article, we evaluated serum F-actin as a biomarker in stroke severity and early neurological deterioration (END) in acute ischemic stroke. METHODS: In this study, serum F-actin was measured in consecutively collected 140 AIS patients and 144 healthy controls matched in gender and age by ELISA. Early neurological deterioration (END) was defined as the deterioration of neurological dysfunction within 72 hours of admission, with an increase of ≥ 4 points in the NIHSS score. Severe stroke was defined as a NIHSS score>8 at admission. RESULTS: The serum F-actin level in AIS was significantly higher than healthy controls (p = 0.041). In large-artery atherosclerosis stroke and cardioembolic stroke, serum F-actin were significantly higher than that in small artery occlusion stroke (padjust = 0.019, padjust < 0.001, respectively).F-actin level above the critical value (>1.37 µg/L) was significantly associated with severe stroke (OR, 3.015; 95 %CI, 1.014-8.963; p = 0.047) . In addition, elevated level of F-actin was significantly associated with END (OR, 1.323; 95 % CI, 1.001-1.747, p = 0.049). When the level of F-actin was above the critical value (>2.17 µg/L), its association with END remained significant (OR, 6.303; 95 %CI, 2.160-18.394; p < 0.001) . CONCLUSION: F-actin is an important blood biomarker in the early stage of AIS, and high levels of F-actin are valuable in determining the severity of stroke and predicting early neurological deterioration.

Optimization of Torque-Control Model for Quasi-Direct-Drive Knee Exoskeleton Robots Based on Regression Forecasting.

The choice of torque curve in lower-limb enhanced exoskeleton robots is a key problem in the control of lower-limb exoskeleton robots. As a human-machine coupled system, mapping from sensor data to joint torque is complex and non-linear, making it difficult to accurately model using mathematical tools. In this research study, the knee torque data of an exoskeleton robot climbing up stairs were obtained using an optical motion-capture system and three-dimensional force-measuring tables, and the inertial measurement unit (IMU) data of the lower limbs of the exoskeleton robot were simultaneously collected. Nonlinear approximations can be learned using machine learning methods. In this research study, a multivariate network model combining CNN and LSTM was used for nonlinear regression forecasting, and a knee joint torque-control model was obtained. Due to delays in mechanical transmission, communication, and the bottom controller, the actual torque curve will lag behind the theoretical curve. In order to compensate for these delays, different time shifts of the torque curve were carried out in the model-training stage to produce different control models. The above model was applied to a lightweight knee exoskeleton robot. The performance of the exoskeleton robot was evaluated using surface electromyography (sEMG) experiments, and the effects of different time-shifting parameters on the performance were compared. During testing, the sEMG activity of the rectus femoris (RF) decreased by 20.87%, while the sEMG activity of the vastus medialis (VM) increased by 17.45%. The experimental results verify the effectiveness of this control model in assisting knee joints in climbing up stairs.

Machine learning-based nomogram to predict poor response to overnight orthokeratology in Chinese myopic children: A multicentre, retrospective study.

PURPOSE: To develop and validate an effective nomogram for predicting poor response to orthokeratology. METHODS: Myopic children (aged 8-15 years) treated with orthokeratology between February 2018 and January 2022 were screened in four hospitals of different tiers (i.e. municipal and provincial) in China. Potential predictors included 32 baseline clinical variables. Nomogram for the outcome (1-year axial elongation ≥0.20 mm: poor response; <0.20 mm: good response) was computed from a logistic regression model with the least absolute shrinkage and selection operator. The data from the First Affiliated Hospital of Chengdu Medical College were randomly assigned (7:3) to the training and validation cohorts. An external cohort from three independent multicentre was used for the model test. Model performance was assessed by discrimination (the area under curve, AUC), calibration (calibration plots) and utility (decision curve analysis). RESULTS: Between January 2022 and March 2023, 1183 eligible subjects were screened from the First Affiliated Hospital of Chengdu Medical College, then randomly divided into training (n = 831) and validation (n = 352) cohorts. A total of 405 eligible subjects were screened in the external cohort. Predictors included in the nomogram were baseline age, spherical equivalent, axial length, pupil diameter, surface asymmetry index and parental myopia (p < 0.05). This nomogram demonstrated excellent calibration, clinical net benefit and discrimination, with the AUC of 0.871 (95% CI 0.847-0.894), 0.863 (0.826-0.901) and 0.817 (0.777-0.857) in the training, validation and external cohorts, respectively. An online calculator was generated for free access (http://39.96.75.172:8182/#/nomogram). CONCLUSION: The nomogram provides accurate individual prediction of poor response to overnight orthokeratology in Chinese myopic children.

Ca 2+ -sensor ALG-2 engages ESCRTs to enhance lysosomal membrane resilience to osmotic stress.

Lysosomes are central players in cellular catabolism, signaling, and metabolic regulation. Cellular and environmental stresses that damage lysosomal membranes can compromise their function and release toxic content into the cytoplasm. Here, we examine how cells respond to osmotic stress within lysosomes. Using sensitive assays of lysosomal leakage and rupture, we examine acute effects of the cathepsin C-metabolized osmotic disruptant glycyl-L-phenylalanine 2-naphthylamide (GPN). Our findings reveal that widely used concentrations of GPN rupture only a small fraction of lysosomes, but surprisingly trigger Ca 2+ release from nearly all. Chelating cytoplasmic Ca 2+ using BAPTA makes lysosomes more likely to rupture under GPN-induced stress, suggesting that Ca 2+ plays a role in protecting or rapidly repairing lysosomal membranes. Mechanistically, we establish that GPN causes the Ca 2+ -sensitive protein Apoptosis Linked Gene-2 (ALG-2) and interacting ESCRT proteins to redistribute onto lysosomes, improving their resistance to membrane stress created by GPN as well as the lysosomotropic drug chlorpromazine. Furthermore, we show that activating the cation channel TRPML1, with or without blocking the endoplasmic reticulum Ca 2+ pump, creates local Ca 2+ signals that protect lysosomes from rupture by recruiting ALG-2 and ESCRTs without any membrane damage. These findings reveal that Ca 2+ , through ALG-2, helps bring ESCRTs to lysosomes to enhance their resilience and maintain organelle integrity in the face of osmotic stress. SIGNIFICANCE: As the degradative hub of the cell, lysosomes are full of toxic content that can spill into the cytoplasm. There has been much recent interest in how cells sense and repair lysosomal membrane damage using ESCRTs and cholesterol to rapidly fix "nanoscale damage". Here, we extend understanding of how ESCRTs contribute by uncovering a preventative role of the ESCRT machinery. We show that ESCRTs, when recruited by the Ca 2+ -sensor ALG-2, play a critical role in stabilizing the lysosomal membrane against osmotically-induced rupture. This finding suggests that cells have mechanisms not just for repairing but also for actively protecting lysosomes from stress-induced membrane damage.

Multivalent Fluorinated Nanorings for On-Cell 19F NMR.

The design of imaging agents with a high fluorine content is necessary for overcoming the challenges of low sensitivity in 19F magnetic resonance imaging (MRI)-based molecular imaging. Chemically self-assembled nanorings (CSANs) provide a strategy to increase the fluorine content through multivalent display. We previously reported an 19F NMR-based imaging tracer, in which case a CSAN-compatible epidermal growth factor receptor (EGFR)-targeting protein E1-dimeric dihydrofolate (E1-DD) was bioconjugated to a highly fluorinated peptide. Despite good 19F NMR performance in aqueous solutions, a limited signal was observed in cell-based 19F NMR using this monomeric construct, motivating further design. Here, we design several new E1-DD proteins bioconjugated to peptides of different fluorine contents. Flow cytometry analysis was used to assess the effect of variable fluorinated peptide sequences on the cellular binding characteristics. Structure-optimized protein, RTC-3, displayed an optimal spectral performance with high affinity and specificity for EGFR-overexpressing cells. To further improve the fluorine content, we next engineered monomeric RTC-3 into CSAN, η-RTC-3. With an approximate eightfold increase in the fluorine content, multivalent η-RTC-3 maintained high cellular specificity and optimal 19F NMR spectral behavior. Importantly, the first cell-based 19F NMR spectra of η-RTC-3 were obtained bound to EGFR-expressing A431 cells, showing a significant amplification in the signal. This new design illustrated the potential of multivalent fluorinated CSANs for future 19F MRI molecular imaging applications.

Continuous production of bimetallic nanoparticles on carbon nanotubes based on 3D-printed microfluidics.

Nanoparticle-functionalized carbon nanotubes are promising in many research fields, especially in sensing, due to their intriguing performance in catalysis. However, these nanomaterials are mainly produced through batch processes under harsh conditions, thus encountering inherent limitations of low throughput and uncontrollable morphology of functional nanoparticles (NPs). In this work, we propose a method for high-yield and continuous production of bimetallic (Pt-Pd) NPs on multi-walled carbon nanotubes (MWCNTs) at room temperature through a custom 3D-printed microfluidic platform. A homogenous particle nucleation and growth environment could be created on the microfluidic platform that was equipped with two 3D-printed micromixers. Pt-Pd NPs loaded on MWCNTs were prepared in the microfluidic platform with high throughput and controlled size, dispersity and composition. The synthetic parameters for these nanocomposites were investigated to optimize their electrocatalytic performance. The optimized nanocomposites exhibited excellent electrocatalytic activity with exceptional sensitivity and wide detection range, superior to their counterparts prepared via conventional approaches. This method proposed here could be further adapted for manufacturing other catalyst support materials, opening more avenues for future large-scale production and catalytic investigation of functional nanomaterials.

Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy.

The human placenta has a vital role in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA sequencing and single-nucleus ATAC sequencing analyses of human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their correspondence with human trophoblast stem cell (hTSC)-derived STB. Furthermore, we identified transcription factors associated with diverse STB nuclear lineages through their gene regulatory networks and experimentally confirmed their function in hTSC and trophoblast organoid-derived STBs. Together, our data provide insights into the heterogeneity of human STB and represent a valuable resource for interpreting associated pregnancy complications.

Fast System Matrix Generation Based on Single Angle Calibration in Open-Sided Field Free Line Magnetic Particle Imaging.

OBJECTIVE: Open-sided field-free line magnetic particle imaging (OS FFL MPI) is a novel medical imaging system configuration that has received significant attention in recent years. However, the measurement-based system matrix (SM) image reconstruction for OS FFL MPI typically requires multiple angle calibration (MAC), which is time-consuming in practice. METHODS: To address this issue, we propose a fast 2D SM generation method that requires only a single angle calibration (SAC). The SAC method exploits the rotational invariance of the system function. Based on the measured single angle system function, the system function is rotated to generate system functions at other angles, and then the SM for image reconstruction is constructed. Then, we conducted various simulation experiments and built an OS FFL MPI scanner to evaluate the proposed SAC method. RESULTS: The experiments demonstrating the effectiveness of SAC in reducing calibration workload, requiring fewer scanning numbers while maintaining a similar image reconstruction quality compared to MAC method. Furthermore, the SM generated by SAC produces consistent imaging results with the SM generated by MAC, regardless of the interpolation algorithms, the number of rotation angles, or the signal-to-noise ratios employed in phantom imaging experiments. CONCLUSION: SAC has been experimentally verified to reduce acquisition time while maintaining accurate and robust reconstruction performance. SIGNIFICANCE: The significance of SAC lies in its contribution to improving calibration efficiency in OS FFL MPI, potentially facilitating the implementation of MPI in a wider range of applications.

Humanized mouse models: A valuable platform for preclinical evaluation of human cancer.

Animal models are routinely employed to assess the treatments for human cancer. However, due to significant differences in genetic backgrounds, traditional animal models are unable to meet bioresearch needs. To overcome this restriction, researchers have generated and optimized immunodeficient mice, and then engrafted human genes, cells, tissues, or organs in mice so that the responses in the model mice could provide a more reliable reference for treatments. As a bridge connecting clinical application and basic research, humanized mice are increasingly used in the preclinical evaluation of cancer treatments, particularly after gene interleukin 2 receptor gamma mutant mice were generated. Human cancer models established in humanized mice support exploration of the mechanism of cancer occurrence and provide an efficient platform for drug screening. However, it is undeniable that the further application of humanized mice still faces multiple challenges. This review summarizes the construction approaches for humanized mice and their existing limitations. We also report the latest applications of humanized mice in preclinical evaluation for the treatment of cancer and point out directions for future optimization of these models.

Polyarylisocyanides Derived from an Alkyne-Pd(II) Catalyst as Robust Alignment Media with Excellent Enantiodiscimination.

The development of chiral alignment media for measuring anisotropic NMR parameters provides an opportunity to determine the absolute configuration of chiral molecules without the need for derivatization. However, chiral alignment media with a high and robust enantiodiscriminating property for a wide range of chiral molecules are still scarce. In this study, we synthesized cholesterol-end-functionalized helical polyisocyanides from a chiral monomer using a cholesterol-based alkyne-Pd(II) initiator. These stereoregular polyisocyanides form stable and weak anisotropic lyotropic liquid crystals (LLCs) in dichloromethane systems, exhibiting highly optical activities in both single left- and right-handed helices. The preparation process of the media was straightforward, and the aligning property of the LLCs could be controlled by adjusting the concentration and temperature. Using the chiral polyisocyanides, we extracted the residual dipolar coupling for an enantiomeric pair of isopinocampheol (IPC), as well as a number of pharmaceutical molecules, demonstrating excellent enantiodiscriminating properties for a broad range of chiral compounds.

Effect of low dose laser cycloplasty on deepening anterior chamber in chronic angle-closure glaucoma.

AIM: To describe the outcome of using low-dose laser cycloplasty (LCP) in chronic angle-closure glaucoma (CACG). METHODS: A retrospective case series. Medical charts of CACG patients who underwent LCP in the Eye Hospital of Wenzhou Medical University were reviewed. The main outcomes included intraocular pressure (IOP), the number of glaucoma medication, anterior segment parameters and surgery-related complications. RESULTS: A total of 7 eyes of 7 CACG patients (age 38.9±11.0y) underwent LCP with a mean follow-up of 27.1±13.7mo (range 16-48mo). Following LCP, mean IOP and glaucoma medications decreased from 26.1±6.1 mm Hg with 3.1±1.1 glaucoma medications pre-treatment to 14.9±3.1 mm Hg (P=0.027) with 0.4±1.1 glaucoma medications (P=0.001) at final follow-up. The anterior chamber depth (ACD), angle opening distance500 and trabecular-iris angle increased from 1.65±0.33 mm, 0.05 mm (range 0-0.30 mm) and 5.1° (range, 0-31.97°) at baseline to 1.98±0.43 mm (P=0.073), 0.53 mm (range 0.42-0.91 mm, P=0.015), 45.9° (range, 40.2°-59.4°, (P=0.015) in the long-term follow-up, respectively. The deepening of ACD and reopening of anterior chamber angle (ACA) was observed in 6 eyes (85.7%). CONCLUSION: LCP is a promising treatment option for patients with CACG via reducing IOP and glaucoma medication without serious complications. In addition, LCP can bring a significant deepening in ACD and reopening of ACA.

Chimeric Antigen Receptor-T Cell Therapy Decreases Distant Metastasis and Inhibits Local Recurrence Post-surgery in Mice.

Distant metastasis and primary tumor relapse are the two main hurdles to the success of surgical treatment for cancer patients. Circulating tumor cells (CTCs) and incomplete surgical resection are the primary cause of distant metastasis and local recurrence of tumors, respectively. Chimeric antigen receptor (CAR)-modified T cells target residual carcinomas and CTCs hold the potential to inhibit primary recurrence and reduce tumor metastasis, but the experimental evidence is lacking. Here, we developed a surgery-induced tumor metastasis model in immunocompetent mice to investigate the efficacy of CAR-T cells therapy in preventing metastasis and local recurrence. We observed that subcutaneous tumor resection has induced a large number of CTCs intravasated into circulation. EpCAM-specific CAR-T was effective in clearing CTCs following surgical removal of the tumor. This resulted in less pulmonary metastasis and longer survival in mice when compared to mice treated with surgery followed by Mock-T cells infusion. In addition, the local relapse was obviously inhibited at the surgical site followed by EpCAM-CAR-T cell treatment. This study demonstrated that CAR-T cell therapy can be an adjuvant treatment following surgery to prevent tumor metastasis and inhibit primary tumor relapse for cancer patients.