Elastase-targeting biomimic nanoplatform for neurovascular remodeling by inhibiting NETosis mediated AlM2 inflammasome activation in ischemic stroke.

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored. Herein, a biomimic multifunctional nanoplatform (HM@ST/TeTeLipos) was developed for active NE targeting and IS treatment. The core of the HM@ST/TeTeLipos consisted of sivelestat-loaded ditelluride-containing liposomes with ROS-responsive and NE-inhibiting properties. The outer shell was composed of platelet-neutrophil hybrid membrane vesicles (HMVs), which acted to hijack neutrophils and neutralize proinflammatory cytokines. Our studies revealed that HM@ST/TeTeLipos could effectively inhibit NE activity, thereby suppressing the release of NETs, impeding the activation of the AIM2 inflammasome, and consequently redirecting the immune response away from a pro-inflammatory M1 microglia phenotype. This resulted in enhanced neurovascular remodeling, reduced BBB disruption, and diminished neuroinflammation, ultimately promoting neuron survival. We believe that this innovative approach holds significant potential for improving the treatment of IS and various NE-mediated inflammatory diseases.

A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy.

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

Exposure to organophosphate esters and early menopause: A population-based cross-sectional study.

Organophosphate esters (OPEs), increasingly used as new flame retardants and plasticizers in various products, have been found to have reproductive toxicity with overt endocrine disruption potential, yet the relationship between OPEs and early menopause remains unexplored. In the present study, we included 2429 women who participated in the U.S. National Health and Nutrition Examination Survey data (2011-2020) and had data of five urinary OPE metabolite levels and information of menopause characteristics, to investigate the associations of OPEs exposure with premature ovarian insufficiency (POI) and age of menopause. Multivariable adjusted linear and logistic regression were used to assess the associations of urinary OPE metabolites with age of menopause and POI, respectively. Quantile g computation (QGC) models were used to assess the relative contribution of individual metabolites to associations of OPE metabolites mixture. After adjusting for covariates, urinary bis(2-chloroethyl) phosphate (BCEP) concentration was inversely associated with menopause age (ß = - 0.21; 95% confidence interval (CI): 0.41, - 0.002). Higher urinary BCEP level (>median) was associated with earlier age at menopause (ß = -1.14, 95% CI: 1.83, - 0.46), and elevated odds of having POI (OR = 1.93; 95% CI: 1.02, 3.66). These associations were robust to the further adjustment of cardiometabolic diseases and related traits (e.g., body mass index). Further QGC analyses confirmed that BCEP was the dominant metabolite contributing most to the associations of OPEs mixture with age of menopause (weight = 49.5%) and POI (weight = 75.1%). No significant associations were found for the other four OPE metabolites. In this cross-sectional study, urinary BCEP level was associated with earlier menopause and increased odds of POI, highlighting the potential negative impacts of this chemical and its parent compound tris(2-chloroethyl) phosphate on ovarian function. Further studies are required to validate our findings and reveal potential underlying mechanisms.

Wnt7b acts in concert with Wnt5a to regulate tissue elongation and planar cell polarity via noncanonical Wnt signaling.

Intercellular signaling mediated by evolutionarily conserved planar cell polarity (PCP) proteins aligns cell polarity along the tissue plane and drives polarized cell behaviors during tissue morphogenesis. Accumulating evidence indicates that the vertebrate PCP pathway is regulated by noncanonical, ß-catenin-independent Wnt signaling; however, the signaling components and mechanisms are incompletely understood. In the mouse hearing organ, both PCP and noncanonical Wnt (ncWnt) signaling are required in the developing auditory sensory epithelium to control cochlear duct elongation and planar polarity of resident sensory hair cells (HCs), including the shape and orientation of the stereociliary hair bundle essential for sound detection. We have recently discovered a Wnt/G-protein/PI3K pathway that coordinates HC planar polarity and intercellular PCP signaling. Here, we identify Wnt7b as a ncWnt ligand acting in concert with Wnt5a to promote tissue elongation in diverse developmental processes. In the cochlea, Wnt5a and Wnt7b are redundantly required for cochlear duct coiling and elongation, HC planar polarity, and asymmetric localization of core PCP proteins Fzd6 and Dvl2. Mechanistically, Wnt5a/Wnt7b-mediated ncWnt signaling promotes membrane recruitment of Daple, a nonreceptor guanine nucleotide exchange factor for Gαi, and activates PI3K/AKT and ERK signaling, which promote asymmetric Fzd6 localization. Thus, ncWnt and PCP signaling pathways have distinct mutant phenotypes and signaling components, suggesting that they act as separate, parallel pathways with nonoverlapping functions in cochlear morphogenesis. NcWnt signaling drives tissue elongation and reinforces intercellular PCP signaling by regulating the trafficking of PCP-specific Frizzled receptors.

Angiopep-2 conjugated biomimetic nano-delivery system loaded with resveratrol for the treatment of methamphetamine addiction.

Methamphetamine (METH) addiction can damage the central nervous system, resulting in cognitive impairment and memory deficits. Low target effects have limited the utility of anti-addiction drugs because the presence of the blood-brain barrier hinders the effective delivery of drugs to the brain. Angiopep-2 can recognize and target low-density lipoprotein receptor-associated protein 1 (LRP-1) on the surface of cerebral capillary endothelial cells, causing cross-cell phagocytosis, and thus has high blood-brain barrier transport capacity. Resveratrol (RSV) has been found to be a neuroprotective agent in many nervous system diseases. In our study, we modified Angiopep-2 on the surface of the erythrocyte membrane to obtain a modified erythrocyte membrane (Ang-RBCm) and coated RSV-loaded poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG) nanoparticles with Ang-RBCm (Ang-RBCm@RSVNPs) to treat METH addiction. Our results showed that Ang-RBCm@RSVNPs can penetrate the blood-brain barrier and accumulate in the brain better than free RSV. Besides, mice treatetd with Ang-RBCm@RSVNPs showed less preference to METH-paired chamber and no noticeable tissue toxicity or abnormality was found in H&E staining images. Electrophysiological experiments demonstrated Ang-RBCm@RSVNPs could elevate synaptic plasticity impaired by METH. These indicated that Ang-RBCm@RSVNPs has better anti-addiction and neuroprotective effects. Therefore, Ang-RBCm@RSVNPs has great potential in the treatment of METH addiction.

Kidney targeting and modulating macrophage polarization through AMPK signaling: Therapeutic mechanism of berberine in uric acid nephropathy.

Uric acid nephropathy (UAN), caused by a common metabolic disorder resulting from hyperuricemia (HUA), has an increasing incidence. Previous studies have shown that berberine (BBR) has clear urate-lowering and anti-inflammatory effects in UAN mice, but its mechanism needs to be further clarified. Therefore, Potassium Oxonate (PO) combined with hypoxanthine (HX) induced UAN mice model and MSU induced THP-1 cells polarization model were adopted to investigate the mechanism of BBR on UAN in terms of tissue distribution and molecular pharmacology. Study unveiled that BBR was first found to bind to red blood cells (RBCs), which were recognized and phagocytosed by monocytes, then recruited by the injured kidney. Subsequently, BBR was enriched and functional in damaged kidney. The results of in vivo experiments revealed that, BBR reduced UA, BUN, CRE levels as well as the release of TNF-α, IL-1ß, IL-18 and IL-6, and alleviated renal injury in UAN mice, as consistent with previous studies. Additionally, BBR decreased MCP-1 expression, while diminishing macrophage infiltration and decreasing M1 proportion as determined by RT-qPCR. In vitro experiments, demonstrated that MSU promoted inflammatory polarization of THP-1 cells, while BBR reduced synthesis of inflammatory factors and inhibited MSU-induced inflammatory polarization. These effects of BBR were dependent on AMPK activation along with indirect inhibition of NF-κB signaling pathway mediated. However, the anti-inflammatory and macrophage polarization regulation effects of BBR were completely reversed upon administration of Compound C, an AMPK inhibitor. Therefore, BBR ameliorated kidney injury via regulating macrophage polarization through AMPK, which has therapeutic potential for UAN patients.

TTFDNet: Precise Depth Estimation from Single-Frame Fringe Patterns.

This work presents TTFDNet, a transformer-based and transfer learning network for end-to-end depth estimation from single-frame fringe patterns in fringe projection profilometry. TTFDNet features a precise contour and coarse depth (PCCD) pre-processor, a global multi-dimensional fusion (GMDF) module and a progressive depth extractor (PDE). It utilizes transfer learning through fringe structure consistency evaluation (FSCE) to leverage the transformer's benefits even on a small dataset. Tested on 208 scenes, the model achieved a mean absolute error (MAE) of 0.00372 mm, outperforming Unet (0.03458 mm) models, PDE (0.01063 mm) and PCTNet (0.00518 mm). It demonstrated precise measurement capabilities with deviations of ~90 µm for a 25.4 mm radius ball and ~6 µm for a 20 mm thick metal part. Additionally, TTFDNet showed excellent generalization and robustness in dynamic reconstruction and varied imaging conditions, making it appropriate for practical applications in manufacturing, automation and computer vision.

Pyroptosis Signature Gene CHMP4B Regulates Microglia Pyroptosis by Inhibiting GSDMD in Alzheimer's Disease.

In this study, we aimed to work through the key genes involved in the process of pyroptosis in Alzheimer's disease (AD) to identify potential biomarkers using bioinformatics technology and further explore the underlying molecular mechanisms. The transcriptome data of brain tissue in AD patients were screened from the GEO database, and pyroptosis-related genes were analyzed. The functions of differential genes were analyzed by enrichment analysis and protein-protein interaction. The diagnostic model was established using LASSO and logistic regression analysis, and the correlation of clinical data was analyzed. Based on single-cell analysis of brain tissues of patients with AD, immunofluorescence and western blotting were used to explore the key cells affected by the hub gene. After GSEA, qRT-PCR, western blotting, LDH, ROS, and JC-1 were used to investigate the potential mechanism of the hub gene on pyroptosis. A total of 15 pyroptosis differentially expressed genes were identified. A prediction model consisting of six genes was established by LASSO and logistic regression analysis, and the area under the curve was up to 0.81. As a hub gene, CHMP4B was negatively correlated with the severity of AD. CHMP4B expression was decreased in the hippocampal tissue of patients with AD and mice. Single-cell analysis showed that CHMP4B was downregulated in AD microglia. Overexpression of CHMP4B reduced the release of LDH and ROS and restored mitochondrial membrane potential, thereby alleviating the inflammatory response during microglial pyroptosis. In summary, CHMP4B as a hub gene provides a new strategy for the diagnosis and treatment of AD.

Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system.

Our sense of hearing is critically dependent on the spiral ganglion neurons (SGNs) that connect the sound receptors in the organ of Corti (OC) to the cochlear nuclei of the hindbrain. Type I SGNs innervate inner hair cells (IHCs) to transmit sound signals, while type II SGNs (SGNIIs) innervate outer hair cells (OHCs) to detect moderate-to-intense sound. During development, SGNII afferents make a characteristic 90-degree turn toward the base of the cochlea and innervate multiple OHCs. It has been shown that the Planar Cell Polarity (PCP) pathway acts non-autonomously to mediate environmental cues in the cochlear epithelium for SGNII afferent turning towards the base. However, the underlying mechanisms are unknown. Here, we present evidence that PCP signaling regulates multiple downstream effectors to influence cell adhesion and the cytoskeleton in cochlear supporting cells (SCs), which serve as intermediate targets of SGNII afferents. We show that the core PCP gene Vangl2 regulates the localization of the small GTPase Rac1 and the cell adhesion molecule Nectin3 at SC-SC junctions through which SGNII afferents travel. Through in vivo genetic analysis, we also show that loss of Rac1 or Nectin3 partially phenocopied SGNII peripheral afferent turning defects in Vangl2 mutants, and that Rac1 plays a non-autonomous role in this process in part by regulating PCP protein localization at the SC-SC junctions. Additionally, epistasis analysis indicates that Nectin3 and Rac1 likely act in the same genetic pathway to control SGNII afferent turning. Together, these experiments identify Nectin3 and Rac1 as novel regulators of PCP-directed SGNII axon guidance in the cochlea.

Quaternary pulse width modulation based ultra-high frame rate scene projector used for hard-ware-in-the-loop testing.

The scene projector (SP) can provide simulated scene images with same optical characteristics as the real scenes to evaluate imaging systems in hard-ware-in-the-loop (HWIL) simulation testing. The single scene generation device (SGD) based SP typically projects 8-bit images at 220 fps, which is insufficient to fulfill the requirements of ultra-high frame rate imaging systems, such as star trackers and space debris detectors. In this paper, an innovative quaternary pulse width modulation (PWM) based SP is developed and implemented to realize the ultra-high frame rate projection. By optically overlapping modulation layers of two digital micro-mirror devices (DMDs) in parallel, and illuminating them with light intensities, a quaternary SGD is built up to modulate quaternary digit-planes (QDs) with four grayscale levels. And the quaternary digit-plane de-composition (QDD) is adopted to decompose an 8-bit image into 4 QDs. In addition, the exposure time of each QD is controlled by quaternary PWM, and the base time is optimized to 8 µs. The experimental results prove that the total exposure time of all QDs sequentially modulated by quaternary PWM is approximately 760 µs, namely projecting 8-bit images at 1300 fps. The quaternary PWM using two DMDs in parallel dramatically improves the grayscale modulation efficiency compared to the existing projection technologies, which provides a new approach for the SP design with ultra-high frame rate.

Simulation and On-Site Detection of the Failure Characteristics of Overlying Strata under the Mining Disturbance of Coal Seams with Thin Bedrock and Thick Alluvium.

When mining deep coal seams with thin bedrock and thick alluvium, the collapse and fracture of thin bedrock layers may cause geological disasters, such as water inrush and sand inrush of the mining face. Comprehensively obtaining the response data of coal mining and reasonably analyzing the failure characteristics of overlying strata are helpful in guiding safe production. In this study, the caving zone heights of overlying strata are obtained by field detection during layered mining. Then, the caving zone heights during the once-full-height mining are evaluated by theoretical analysis. Further, the force and failure characteristics of coal-rock structures under different mining conditions are compared by the simulation detection and analysis. Finally, the results of on-site observation, theoretical analysis, and simulation detection are compared and discussed, and an optimized mining technology is proposed to ensure safe mining. The research shows the caving zone heights of on-site and simulation detections are, respectively, 14.65 m and 13.5 m during bottom-layer mining, which is larger than the caving zone heights of the top-layer coal mining. During once-full-height mining, the maximum caving zone height of simulation detection is 21 m, which is in between two standard results. For the mechanical responses of an aquiclude clay layer under thick loose alluvium, the maximum disturbance displacement of clay aquiclude is 5.8 m during layered mining, which is slightly larger than the disturbance displacement of once full-height mining; however, the maximum stress of the clay layer is 25 MPa during once-full-height mining, which is larger than the maximum stress of clay layer during layered mining. For the clay aquiclude failure, the clay layer during layered mining is in the deflection deformation area, and there is no obvious fracture structure to inrush the water and sand of thick loose alluvium; however, the clay layer during once-full-height mining is prone to produce obvious fracture structure. Therefore, the layered mining technology can effectively reduce and prevent the water/sand inrush disaster of mining working face.

Direct space-time manipulation mechanism for spatio-temporal coupling of ultrafast light field.

Traditionally, manipulation of spatiotemporal coupling (STC) of the ultrafast light fields can be actualized in the space-spectrum domain with some 4-f pulse shapers, which suffers usually from some limitations, such as spectral/pixel resolution and information crosstalk associated with the 4-f pulse shapers. This work introduces a novel mechanism for direct space-time manipulation of ultrafast light fields to overcome the limitations. This mechanism combines a space-dependent time delay with some spatial geometrical transformations, which has been experimentally proved by generating a high-quality STC light field, called light spring (LS). The LS, owing a broad topological charge bandwidth of 11.5 and a tunable central topological charge from 2 to -11, can propagate with a stable spatiotemporal intensity structure from near to far fields. This achievement implies the mechanism provides an efficient way to generate complex STC light fields, such as LS with potential applications in information encryption, optical communication, and laser-plasma acceleration.

A Spatial Multi-Modal Dissection of Host-Microbiome Interactions within the Colitis Tissue Microenvironment.

The intricate and dynamic interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host features and its microbiome across multiple spatial modalities. We demonstrate MicroCart by comprehensively investigating the alterations in both gut host and microbiome components in a murine model of colitis by coupling MicroCart with spatial proteomics, transcriptomics, and glycomics platforms. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, and bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multiomics.

All-Cause Mortality Differentials by Diabetes Status and Serum Neurofilament Light Chain Levels in U.S. General Adults.

CONTEXT: Neurofilament light chain (sNFL) increases in patients with diabetes and is associated with death. OBJECTIVE: To examine whether sNFL mediates associations of diabetes with all-cause mortality and the extent of interaction or joint relations of sNFL and diabetes with mortality. DESIGN: Population based cohort study. SETTING: 2013-2014 cycle of National Health and Nutrition Examination Survey. PARTICIPANTS: 2071 adults aged 20 to 75 years with measurements of sNFL. INTERVENTION(S): sNFL was lg transformed (LgNfl). Participants were featured whether LgNfl was higher than 1.48pg/ml or diagnosed with diabetes. MAIN OUTCOME MEASURE: All-cause mortality was the primary outcome obtained through linkage to registries. RESULTS: During a median follow-up of 6.1years, 85 participants died. Incidence rates [per 1000 person-years (95% CI)] of all-cause mortality were 27.78 (19.98∼35.58) in adults with LgNfl>1.48pg/ml and diabetes, 9.01 (1.99∼16.03) in adults with LgNfl>1.48pg/ml but no diabetes, 3.07 (1.01∼5.13) in adults with diabetes and LgNfl≤1.48pg/ml, and 2.21 (1.15∼3.27) in adults without diabetes and LgNfl≤1.48pg/ml. Significant interaction but not mediation was observed between LgNfl and diabetes. Compared with adults of no diabetes and LgNfl≤1.48pg/ml, those with diabetes and LgNfl > 1.48pg/ml had higher risks of all-cause mortality (Hazard ratio, 95%CI; 7.06, 3.52∼14.16). CONCLUSIONS: In general US adults with diabetes, elevated sNFL associated with higher all-cause mortality specifically, supporting an important role of sNFL in predicting health outcome in those with diabetes.

Touchless Thermosensation Enabled by Flexible Infrared Photothermoelectric Detector for Temperature Prewarning Function of Electronic Skin.

Artificial skin, endowed with the capability to perceive thermal stimuli without physical contact, will bring innovative interactive experiences into smart robotics and augmented reality. The implementation of touchless thermosensation, responding to both hot and cold stimuli, relies on the construction of a flexible infrared detector operating in the long-wavelength infrared range to capture the spontaneous thermal radiation. This imposes rigorous requirements on the photodetection performance and mechanical flexibility of the detector. Herein, a flexible and wearable infrared detector is presented, on basis of the photothermoelectric coupling of the tellurium-based thermoelectric multilayer film and the infrared-absorbing polyimide substrate. By suppressing the optical reflection loss and aligning the destructive interference position with the absorption peak of polyimide, the fabricated thermopile detector exhibits high sensitivity to the thermal radiation over a broad source temperature range from -50 to 110 °C, even capable of resolving 0.05 °C temperature change. Spatially resolved radiation distribution sensing is also achieved by constructing an integrated thermopile array. Furthermore, an established temperature prewarning system is demonstrated for soft robotic gripper, enabling the identification of noxious thermal stimuli in a contactless manner. A feasible strategy is offered here to integrate the infrared detection technique into the sensory modality of electronic skin.

Discovery of 2,8-dihydroxyadenine in HUA patients with uroliths and biomarkers for its associated nephropathy.

Currently, it is acknowledged that gout is caused by uric acid (UA). However, some studies have revealed no correlation between gout and UA levels, and growing evidence suggests that 2,8-dihydroxyadenine (2,8-DHA), whose structural formula is similar to UA but is less soluble, may induce gout. Hence, we hypothesized that uroliths from hyperuricemia (HUA) patients, which is closely associated with gout, may contain 2,8-DHA. In this study, 2,8-DHA in uroliths and serum of HUA patients were determined using HPLC. Moreover, bioinformatics was used to investigate the pathogenic mechanisms of 2,8-DHA nephropathy. Subsequently, a mouse model of 2,8-DHA nephropathy established by the gavage administration of adenine, as well as a model of injured HK-2 cells induced by 2,8-DHA were used to explore the pathogenesis of 2,8-DHA nephropathy. Interestingly, 2,8-DHA could readily deposit in the cortex of the renal tubules, and was found in the majority of these HUA patients. Additionally, the differentially expressed genes between 2,8-DHA nephropathy mice and control mice were found to be involved in inflammatory reactions. Importantly, CCL2 and IL-1ß genes had the maximum degree, closeness, and betweenness centrality scores. The expressions of CCL2 and IL-1ß genes were significantly increased in the serum of 24 HUA patients with uroliths, indicating that they may be significant factors for 2,8-DHA nephropathy. Further analysis illustrated that oxidative damage and inflammation were the crucial processes of 2,8-DHA renal injury, and CCL2 and IL-1ß genes were verified to be essential biomarkers for 2,8-DHA nephropathy. These findings revealed further insights into 2,8-DHA nephropathy, and provided new ideas for its diagnosis and treatment.

An N-glycome tissue atlas of 15 human normal and cancer tissue types determined by MALDI-imaging mass spectrometry.

N-glycosylation is an abundant post-translational modification of most cell-surface proteins. N-glycans play a crucial role in cellular functions like protein folding, protein localization, cell-cell signaling, and immune detection. As different tissue types display different N-glycan profiles, changes in N-glycan compositions occur in tissue-specific ways with development of disease, like cancer. However, no comparative atlas resource exists for documenting N-glycome alterations across various human tissue types, particularly comparing normal and cancerous tissues. In order to study a broad range of human tissue N-glycomes, N-glycan targeted MALDI imaging mass spectrometry was applied to custom formalin-fixed paraffin-embedded tissue microarrays. These encompassed fifteen human tissue types including bladder, breast, cervix, colon, esophagus, gastric, kidney, liver, lung, pancreas, prostate, sarcoma, skin, thyroid, and uterus. Each array contained both normal and tumor cores from the same pathology block, selected by a pathologist, allowing more in-depth comparisons of the N-glycome differences between tumor and normal and across tissue types. Using established MALDI-IMS workflows and existing N-glycan databases, the N-glycans present in each tissue core were spatially profiled and peak intensity data compiled for comparative analyses. Further structural information was determined for core fucosylation using endoglycosidase F3, and differentiation of sialic acid linkages through stabilization chemistry. Glycan structural differences across the tissue types were compared for oligomannose levels, branching complexity, presence of bisecting N-acetylglucosamine, fucosylation, and sialylation. Collectively, our research identified the N-glycans that were significantly increased and/or decreased in relative abundance in cancer for each tissue type. This study offers valuable information on a wide scale for both normal and cancerous tissues, serving as a reference for future studies and potential diagnostic applications of MALDI-IMS.

Novel Variants of CEP152 in a Case of Compound-Heterozygous Inheritance of Epilepsy.

Introduction CEP152 encodes protein Cep152, which associates with centrosome function. The lack of Cep152 can cause centrosome duplication to fail. CEP152 mutates, causing several diseases such as Seckel syndrome-5 and primary microencephaly-9. Methods In this study, we reported a patient diagnosed with epilepsy in Tianjin Children's Hospital. We performed clinical examination and laboratory test, and whole-exome sequencing was performed for the proband's and his parents' peripheral blood. The suspected compound-heterozygous variant in the CEP152 gene was verified by Sanger sequencing and quantitative real-time polymerase chain reaction technology. Results We discovered three variants-two of them from CEP152 and one from HPD . The result showed the variants in CEP152 only. The patient presented with seizures frequently. Sanger sequencing showed two novel variants in CEP152 are in exon26 (NM_014985.3 c.3968C > A p.Ser1323*) and in exon16 (NM_014985.3 c.2034_2036del p.Tyr678*). Conclusions We reported a novel compound-heterozygous variant in the CEP152 gene in this study. Most of the phenotypes are Seckel syndrome and primary microencephaly, and the novel variant may cause an atypical phenotype that is epilepsy.

Simulation and Optimization: A New Direction in Supercritical Technology Based Nanomedicine.

In recent years, nanomedicines prepared using supercritical technology have garnered widespread research attention due to their inherent attributes, including structural stability, high bioavailability, and commendable safety profiles. The preparation of these nanomedicines relies upon drug solubility and mixing efficiency within supercritical fluids (SCFs). Solubility is closely intertwined with operational parameters such as temperature and pressure while mixing efficiency is influenced not only by operational conditions but also by the shape and dimensions of the nozzle. Due to the special conditions of supercriticality, these parameters are difficult to measure directly, thus presenting significant challenges for the preparation and optimization of nanomedicines. Mathematical models can, to a certain extent, prognosticate solubility, while simulation models can visualize mixing efficiency during experimental procedures, offering novel avenues for advancing supercritical nanomedicines. Consequently, within the framework of this endeavor, we embark on an extensive review encompassing the application of mathematical models, artificial intelligence (AI) methodologies, and computational fluid dynamics (CFD) techniques within the medical domain of supercritical technology. We undertake the synthesis and discourse of methodologies for calculating drug solubility in SCFs, as well as the influence of operational conditions and experimental apparatus upon the outcomes of nanomedicine preparation using supercritical technology. Through this comprehensive review, we elucidate the implementation procedures and commonly employed models of diverse methodologies, juxtaposing the merits and demerits of these models. Furthermore, we assert the dependability of employing models to compute drug solubility in SCFs and simulate the experimental processes, with the capability to serve as valuable tools for aiding and optimizing experiments, as well as providing guidance in the selection of appropriate operational conditions. This, in turn, fosters innovative avenues for the development of supercritical pharmaceuticals.