Synthesis and structural optimization of oncolytic peptide LTX-315.

Oncolytic peptides represented potential novel candidates for anticancer treatments especially drug-resistant cancer cell lines. One of the most promising and extensively studied is LTX-315, which is considered as the first in class oncolytic peptide and has entered phase I/II clinical trials. Nevertheless, the shortcomings including poor proteolytic stability, moderate anticancer durability and high synthesis costs may hinder the widespread clinical applications of LTX-315. In order to reduce the synthesis costs, as well as develop derivatives possessing both high protease-stability and durable anticancer efficiency, twenty LTX-315-based derived-peptides were designed and efficiently synthesized. Especially, through solid-phase S-alkylation, as well as the optimized peptide cleavage condition, the derived peptides could be prepared with drastically reduced synthesis cost. The in vitro anticancer efficiency, serum stability, anticancer durability, anti-migration activity, and hemolysis effect were systematically investigated. It was found that derived peptide MS-13 exhibited comparable anticancer efficiency and durability to those of LTX-315. Strikingly, the D-type peptide MS-20, which is the enantiomer of MS-13, was demonstrated to possess significantly high proteolytic stability and sustained anticancer durability. In general, the cost-effective synthesis and stability-guided structural optimizations were conducted on LTX-315, affording the highly hydrolysis resistant MS-20 which possessed durable anticancer activity. Meanwhile, this study also provided a reliable reference for the future optimization of anticancer peptides through the solid-phase S-alkylation and L-type to D-type amino acid substitutions.

A Pan-Cancer Analysis to Provide Insight into the Immunological Role and Prognostic Value of HTRA3.

High-temperature requirement factor A3 (HTRA3), a member of the HTRA protein family, is closely associated with apoptosis and plays a crucial role in controlling signal transmission and cancer development. However, the regulatory pathways of HTRA3 in tumors are not fully understood, necessitating a comprehensive analysis of HTRA3 in cancers. In this study, we conducted a multi-omics analysis of HTRA3 in pan-cancer using data from various databases including TCGA, cBioPortal, GeneMANIA, DAVID, TIMER2.0, SangerBox, and RNAactDrug. Our analysis included gene expression, survival prognosis, diagnostic value, mutation, gene-gene interaction, enrichment analysis, and drug sensitivity analysis. We found that HTRA3 is aberrantly expressed in a variety of cancers and significantly correlates with diagnosis, prognosis, TMB, MSI, immune checkpoint (ICP) genes, and drug sensitivity in various cancer types. HTRA3 is involved in a variety of cancer pathways, particularly extracellular matrix (ECM) alterations, and has a potential role in epithelial-mesenchymal transition (EMT). HTRA3 expression is positively correlated with the abundance of cancer-associated fibroblasts (CAFs) and endothelial cells in the tumor microenvironment, and is also positively correlated with immune scores, stromal scores, and ESTIMATE scores in multiple cancers. HTRA3 is often overexpressed in cancer and is associated with poor prognosis and regulation of the tumor's immune response. Therefore, it may serve as a novel biomarker for tumor diagnosis and treatment.

DeepS: Accelerating 3D Mass Spectrometry Imaging via a Deep Neural Network.

Mass spectrometry imaging (MSI) is a powerful methodology that enables the visualization of the spatial distribution of biomolecules, including lipids, peptides, and proteins, from biological tissue sections. While two-dimensional (2D) MSI has been widely reported in various applications, three-dimensional (3D) MSI can enable the mapping of biomolecule distribution in complex biological structures (e.g., organs) with an added dimension. However, traditional 3D MSI techniques are time-consuming since 3D MS images are constructed from 2D MSI analyses of a series of tissue sections. In this study, we propose a 3D MSI workflow, termed DeepS, which uses a 3D sparse sampling network (3D-SSNet) and a sparse sampling strategy to significantly accelerate 3D MSI analyses. Sparsely sampled tissue sections are reconstructed using 3D-SSNet, yielding results comparable to those using full sampling MSI, even at a sampling ratio of 20-30%. The workflow performed well when applied to 3D imaging of a mouse brain with Alzheimer's disease, and combined with transfer learning, it is successfully used for the 3D MSI analyses of more heterogeneous samples, e.g., a mouse brain with glioblastoma and a mouse kidney.

Targeting 14-3-3ζ by a small-molecule compound AI-34 maintains epithelial barrier integrity and alleviates colitis in mice via stabilizing ß-catenin.

Aberrant intestinal epithelial barrier function is the primary pathology of Ulcerative colitis (UC), making it a desirable drug target. In this study, our small-molecule compound AI-34 exerted a significant protective effect in an LPS-induced epithelial barrier injury model. In vitro, AI-34 treatment significantly decreased cell permeability, increased transmembrane resistance, and maintained the junctional protein (ZO-1 and E-cadherin) levels in monolayer cells. Using the LiP-small molecule mapping approach (LiP-SMap), we demonstrated that AI-34 binds to 14-3-3ζ. AI-34 promoted the interaction between 14-3-3ζ and ß-catenin, decreasing the ubiquitination of ß-catenin and thus maintaining intestinal epithelial barrier function. Finally, AI-34 triggered the stabilization of ß-catenin mediated by 14-3-3ζ, provoking a significant improvement in the DSS-induced colitis model. Our findings suggest that AI-34 may be a promising candidate for UC treatment.

Mobility-Modulated Sequential Dissociation Analysis Enables Structural Lipidomics in Mass Spectrometry Imaging.

Spatial lipidomics based on mass spectrometry imaging (MSI) is a powerful tool for fundamental biology studies and biomarker discovery. But the structure-resolving capability of MSI is limited because of the lack of multiplexed tandem mass spectrometry (MS/MS) method, primarily due to the small sample amount available from each pixel and the poor ion usage in MS/MS analysis. Here, we report a mobility-modulated sequential dissociation (MMSD) strategy for multiplex MS/MS imaging of distinct lipids from biological tissues. With ion mobility-enabled data-independent acquisition and automated spectrum deconvolution, MS/MS spectra of a large number of lipid species from each tissue pixel are acquired, at no expense of imaging speed. MMSD imaging is highlighted by MS/MS imaging of 24 structurally distinct lipids in the mouse brain and the revealing of the correlation of a structurally distinct phosphatidylethanolamine isomer (PE 18 : 1_18 : 1) from a human hepatocellular carcinoma (HCC) tissue. Mapping of structurally distinct lipid isomers is now enabled and spatial lipidomics becomes feasible for MSI.

sn-1 Specificity of Lysophosphatidylcholine Acyltransferase-1 Revealed by a Mass Spectrometry-Based Assay.

Lysophosphatidylcholine acyltransferase-1 (LPCAT1) plays a critical role in the remodeling of phosphatidylcholines (PCs) in cellular lipidome. However, evidence is scarce regarding its sn-selectivity, viz. the preference of assembling acyl-Coenzyme A (CoA) at the C1 or C2-hydroxyl on a glycerol backbone because of difficulty to quantify the thus-formed PC sn-isomers. We have established a multiplexed assay to measure both sn- and acyl-chain selectivity of LPCAT1 toward a mixture of acyl-CoAs by integrating isomer-resolving tandem mass spectrometry. Our findings reveal that LPCAT1 shows exclusive sn-1 specificity regardless of the identity of acyl-CoAs. We further confirm that elevated PC 18 : 1/16:0 relative to its sn-isomer results from an increased expression of LPCAT1 in human hepatocellular carcinoma (HCC) tissue as compared to normal liver tissue. MS imaging via desorption electrospray ionization of PC 18 : 1/16:0 thus enables visualization of HCC margins in human liver tissue at a molecular level.

Multiscale feature pyramid network based on activity level weight selection for infrared and visible image fusion.

At present, deep-learning-based infrared and visible image fusion methods have the problem of extracting insufficient source image features, causing imbalanced infrared and visible information in fused images. To solve the problem, a multiscale feature pyramid network based on activity level weight selection (MFPN-AWS) with a complete downsampling-upsampling structure is proposed. The network consists of three parts: a downsampling convolutional network, an AWS fusion layer, and an upsampling convolutional network. First, multiscale deep features are extracted by downsampling convolutional networks, obtaining rich information of intermediate layers. Second, AWS highlights the advantages of the l1-norm and global pooling dual fusion strategy to describe the characteristics of target saliency and texture detail, and effectively balances the multiscale infrared and visible features. Finally, multiscale fused features are reconstructed by the upsampling convolutional network to obtain fused images. Compared with nine state-of-the-art methods via the publicly available experimental datasets TNO and VIFB, MFPN-AWS reaches more natural and balanced fusion results, such as better overall clarity and salient targets, and achieves optimal values on two metrics: mutual information and visual fidelity.

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis.

BACKGROUND: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. METHODS: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). RESULTS: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. CONCLUSIONS: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types.

Formononetin, J1 and J2 have different effects on endothelial cells via EWSAT1-TRAF6 and its downstream pathway.

Formononetin is a natural isoflavone compound found mainly in Chinese herbal medicines such as astragalus and red clover. It is considered to be a typical phytooestrogen. In our previous experiments, it was found that formononetin has a two-way regulatory effect on endothelial cells (ECs): low concentrations promote the proliferation of ECs and high concentrations have an inhibitory effect. To find a specific mechanism of action and provide a better clinical effect, we performed a structural transformation of formononetin and selected better medicinal properties for formononetin modifier J1 and J2 from a variety of modified constructs. The MTT assay measured the effects of drugs on human umbilical vein endothelial cell (HUVEC) activity. Scratch and transwell experiments validated the effects of the drugs on HUVEC migration and invasion. An in vivo assessment effect of the drugs on ovariectomized rats. Long-chain non-coding RNA for EWSAT1, which is abnormally highly expressed in HUVEC, was screened by gene chip, and the effect of the drug on its expression was detected by PCR after the drug was applied. The downstream factors and their pathways were analysed, and the changes in the protein levels after drug treatment were evaluated by Western blot. In conclusion, the mechanism of action of formononetin, J1 and J2 on ECs may be through EWSAT1-TRAF6 and its downstream pathways.

DMSP-Producing Bacteria Are More Abundant in the Surface Microlayer than Subsurface Seawater of the East China Sea.

Microbial production and catabolism of dimethylsulfoniopropionate (DMSP), generating the climatically active gases dimethyl sulfide (DMS) and methanethiol (MeSH), have key roles in global carbon and sulfur cycling, chemotaxis, and atmospheric chemistry. Microorganisms in the sea surface microlayer (SML), the interface between seawater and atmosphere, likely play an important role in the generation of DMS and MeSH and their exchange to the atmosphere, but little is known about these SML microorganisms. Here, we investigated the differences between bacterial community structure and the distribution and transcription profiles of the key bacterial DMSP synthesis (dsyB and mmtN) and catabolic (dmdA and dddP) genes in East China Sea SML and subsurface seawater (SSW) samples. Per equivalent volume, bacteria were far more abundant (~ 7.5-fold) in SML than SSW, as were those genera predicted to produce DMSP. Indeed, dsyB (~ 7-fold) and mmtN (~ 4-fold), robust reporters for bacterial DMSP production, were also far more abundant in SML than SSW. In addition, the SML had higher dsyB transcripts (~ 3-fold) than SSW samples, which may contribute to the significantly higher DMSP level observed in SML compared with SSW. Furthermore, the abundance of bacteria with dmdA and their transcription were higher in SML than SSW samples. Bacteria with dddP and transcripts were also prominent, but less than dmdA and presented at similar levels in both layers. These data indicate that the SML might be an important hotspot for bacterial DMSP production as well as generating the climatically active gases DMS and MeSH, a portion of which are likely transferred to the atmosphere.

Elevated Blood and Urinary ICAM-1 is a Biomarker for Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology. Intercellular cell adhesion molecule-1 (ICAM-1) is critical for leukocyte adhesion to endothelium and migration out of blood vessels and thus participates in many autoimmune diseases. Previous studies of blood and urinary ICAM-1 in SLE have yielded inconsistent results.Methods: The following databases were searched for studies that compared blood and/or urinary ICAM-1 in SLE patients vs. healthy control subjects, and/or in SLE with active vs. inactive diseases: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure and Web of Science. Standardized mean difference (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model when there was significant heterogeneity (assesses using the Cochrane Q test and I2 statistics), and using a fixed-effects model otherwise. Publication bias was assessed using funnel plot and egger text.Results: The initial screening yielded a total of 1,215 articles; 22 articles (14 reporting blood ICAM-1, 7 reporting urinary ICAM-1 and 1 reporting both) were included in the meta-analysis. In comparison to healthy controls, SLE patients had elevated urinary ICAM-1 (SMD: 0.711; 95% CI: 0.521, 0.901) as well as blood ICAM-1 (SMD: 0.725; 95% CI: 0.385, 1.065). Blood ICAM-1 did not differ significantly between active and inactive SLE (SMD: 0.396; 95% CI: -0.556, 1.347).Conclusion: Elevated blood and urinary ICAM-1 is a biomarker for SLE, but does not differentiate active and inactive SLE.

A Meta-Analysis of Cardiovascular Events in Systemic Lupus Erythematosus.

Objective: To identify accurate occurrence and risk of cardiovascular (CV) events (stroke and myocardial infarction [MI]) in patients with systemic lupus erythematosus (SLE). Methods: Systemic literature search in PubMed and additional manual search were performed to obtain interested studies until March 31, 2018. The pooled incidences and risk of stroke and MI were calculated. Results: A total of 24 studies were included in this meta-analysis. For MI, a total of 1,516 SLE patients were reported to had MI (n = 96,154) over a mean follow-up of 9.98 years: incidence 2.0% (95% CI: 1.7-2.4%), i.e. 0.20/100 pyrs; in the five studies, 360 SLE patients (n = 18,943) and 817 controls had MI (n = 111,525), revealing that the risk of MI in SLE population was 3.04 times higher than in the general population (RR = 3.04, 95% CI: 1.81-5.11). For stroke, the incidence of 17 studies during the 10.09 follow-up period using random model was 4.4% (95% CI: 3.6-5.1%), i.e. 0.44/100 pyrs; in the 7 studies, 694 SLE patients (n = 22,594) and 4,034 controls had stroke (n = 255,023), indicating that the risk of MI in SLE population was 1.95 times higher than that in the general population (RR = 1.95, 95% CI: 1.52-2.53). Conclusion: Based on the findings from previous reports, our meta-analysis showed that patients with SLE have been at higher risk of CV events.

Effects of VEGF-ANG-1-PLA nano-sustained release microspheres on proliferation and differentiation of ADSCs.

The improvement of fat graft viability might depend on the presence of multipotent resident adipose derived stem cells (ADSCs) which is the important component of stromal vascular fraction (SVF). Vascular endothelial growth factor (VEGF) and angiogenin-1 (Ang-1) are responsible for neovascularization. However, their half-life is too short to produce a biological effect. We thus investigated whether VEGF-ANG-1-polylactic acid (PLA) microspheres could enhance the angiogenic properties of ADSCs. PLA microspheres containing VEGF and ANG-1 were prepared by in vitro ultrasonic emulsification and characterized according to their encapsulation efficiency (EE), drug-loading rate (DL), particle size, and drug release. The systemic toxicity of empty loaded nanospheres (NPs) and the ability of these microspheres to promote the proliferation and differentiation of ADSCs were evaluated. The EE and DL were above 86% and 0.0288%, respectively [corrected].The drug release was completed after 20 days. Systemic toxicity was verified in ADSCs that received the unloaded NPs. It was observed that ADSCs treated with VEGF-ANG-1-PLA microspheres had an increase in the proliferation and the number of CD31 positive cells. ADSCs proliferation and differentiation toward endothelial cells (ECs) could be enhanced by the addition of VEGF-ANG-1-PLA nano-sustained release microspheres.

Curcumin alleviates hypertrophic scarring by inhibiting fibroblast activation and regulating tissue inflammation.

BACKGROUND: Hypertrophic scar (HS) that can lead to defects in appearance and function is often characterized by uncontrolled fibroblast proliferation and excessive inflammation. Curcumin has been shown to have anti-inflammatory and anti-oxidative effects and to play an anti-fibrotic role by interfering transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathways. AIM: To study the effect and mechanism of curcumin on HS from the perspective of fibroblast activity and inflammation regulation. METHODS: Cell proliferation, migration and the expression of α-smooth muscle actin (α-SMA) of TGF-ß1-induced human dermal fibroblasts (HDFs) treated by curcumin were evaluated using Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine staining, Transwell assay, Western blotting and immunofluorescence, respectively. The expression of TGF-ß1/Smad3 pathway-related molecules (TGF-ß1, TGFß-R1/2, p-Smad3, Smad4) was detected by Western blotting. In a rabbit ear model, hematoxylin and eosin and Masson's staining were conducted to assess scar elevation and collagen deposition, and immunohistochemistry was performed to detect the activation of fibroblasts and infiltration of inflammatory cells. RESULTS: Curcumin inhibited proliferation, migration and α-SMA expression of HDFs in a dose-dependent manner. Curcumin (25 µm mol/L) did not regulate the expression of endogenous TGF-ß1, but suppressed Smad3 phosphorylation and nuclear translocation, leading to lower α-SMA expression. Curcumin also reduced hypertrophic scarring of rabbit ear, accompanied by the inhibited TGF-ß1/Smad3 pathway, inflammatory infiltration and M2 macrophage polarization. CONCLUSION: Curcumin plays an anti-scar role through regulating fibroblast activation and tissue inflammation. Our findings provide scientific reference for the clinical use of curcumin in the treatment of HS.

Comparison research on the therapeutic effects of botulinum toxin type A and stromal vascular fraction gel on hypertrophic scars in the rabbit ear model.

BACKGROUND AND OBJECTIVES: Botulinum toxin type A (BTA) is often used for wrinkles and muscle convulsive diseases due to its blocking of the transmission of nerve impulses. Stromal vascular fraction gel (SVF-gel) prepared from adipose tissue has novel effects on skin depression and poor texture. Both BTA and SVF-gel are proved to possess anti-scar potential. This study aimed to assess and compare their therapeutic effects on hypertrophic scars. MATERIALS AND METHODS: The rabbit ear scar model was established and treated with BTA and SVF-gel, alone or in combination. Gross evaluation using Manchester Scar Scale (MSS) was conducted immediately, 4 and 8 weeks after initial treatment. After tissue sample harvest, histological and Western blot analyses were performed. RESULTS: All the treatments alleviated scar hyperplasia in different degrees by inhibiting fibroblast activation (Ki-67, α-SMA), tissue inflammation (CD45, IL-1ß) and the transforming growth factor-ß1 (TGF-ß1)/Smad3 pathway. Despite an excellent anti-inflammatory effect, improvement of scar appearance and pathological characteristics in SVF-gel-contained groups was not as good as that in BTA-only group, which might be related to the retention of M2-type macrophages (CD163 +) and partial maintenance of TGF-ß1 expression. CONCLUSION: Our data suggest that BTA has better anti-scar efficacy than SVF-gel, and the combination of these two treatments shows no obvious combinatorial effect.

Dispersion characteristics of arc-axis waveguides.

Ultrasonic single mode excitation methods, mode separation algorithms and damage detection applications all require the calculation of the dispersion characteristics of the waveguide. However, existing dispersion calculation methods are mainly applicable to straight-axis waveguides. Therefore, in this paper, a novel semi-analytical finite element method in cylindrical coordinates (SAFEM-CC) is established and we focus on the dispersion characteristics of arc-axis waveguides. The cross-section of the waveguide can have arbitrary complex shapes, and the correctness of this method is verified by the finite element eigenfrequency method. At the same time, this paper takes the example of an arc-axis structure with a square cross-section and investigates the convergence of SAFEM-CC under different numbers of elements, element types, and element orders. This paper also establishes a finite element simulation model to study the waveform transmission law over a wide frequency range and the wave amplitude distribution law within the cross-section of arc-axis waveguides. The dispersion characteristics of arc-axis waveguides at different radii are also investigated. Finally, the correctness of the proposed method and the dispersion characteristics of arc-axis waveguides are verified by a large number of experiments. The main conclusions are as follows: the waveform transmission laws of the guided wave in arc-axis waveguides at each frequency agree with the dispersion curve; the theoretical wavestructure gives the distribution law of the amplitude within the cross-section; when the axis is arc, the displacement of the wavestructure on the inner and outer sides does not have symmetry, and the difference between the left and right sides gradually increases as the radius decreases.

Paeoniflorin attenuates particulate matter-induced acute lung injury by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis through activation of the Nrf2 signaling pathway.

Particulate matter (PM), the main component of air pollutants, emerges as a research hotspot, especially in the area of respiratory diseases. Paeoniflorin (PAE), known as anti-inflammatory and immunomodulatory effects, has been reported to alleviate acute lung injury (ALI). However, the effect of PAE on PM-induced ALI and the underlying mechanisms are still unclear yet. In this study, we established the PM-induced ALI model using C57BL/6J mice and BEAS-2B cells to explore the function of PAE. In vivo, mice were intraperitoneally injected with PAE (100 mg/kg) or saline 1 h before instilled with 4 mg/kg PM intratracheally and were euthanized on the third day. For lung tissues, HE staining and TUNEL staining were used to evaluate the degree of lung injury, ELISA assay was used to assess inflammatory mediators and oxidative stress level, Immunofluorescence staining and western blotting were applied to explore the role of pyroptosis and Nrf2 signaling pathway. In vitro, BEAS-2B cells were pretreated with 100 µM PAE before exposure to 200 µg/ml PM and were collected after 24h for the subsequent experiments. TUNEL staining, ROS staining, and western blotting were conducted to explore the underlying mechanisms of PAE on PM-induced ALI. According to the results, PAE can attenuate the degree of PM-induced ALI in mice and reduce PM-induced cytotoxicity in BEAS-2B cells. PAE can relieve PM-induced excessive oxidative stress and NLRP3 inflammasome-mediated pyroptosis. Additionally, PAE can also activate Nrf2 signaling pathway and inhibition of Nrf2 signaling pathway can impair the protective effect of PAE by aggravating oxidative stress and pyroptosis. Our findings demonstrate that PAE can attenuate PM-induced ALI by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis, which is mediated by Nrf2 signaling pathway.

The Role of Continuous Theta Burst Stimulation on Primary Motor Cortex in Improving Bladder Function in Post-stroke Patients: A Case Report.

Neurogenic bladder (NB) is a frequently encountered post-stroke complication, characterized by symptoms, such as urinary incontinence, dysuria, increased frequency, and urgency. Here, we present a case of a 75-year-old male with urgent urination, frequent urination, urinary incontinence, conspicuous discomfort during urination, and an unpleasant smell in the urine following a stroke. By reviewing the patient's previous medical records of stroke and ruling out other potential causes for bladder dysfunction, a diagnosis of NB could be established. We implemented conventional physical therapy, pelvic floor muscle training with the electromyography biofeedback device, and continuous theta burst stimulation (cTBS) on the contralesional primary motor cortex area to manage bladder function. To the best of our knowledge, this is the first case report on cTBS applied to manage NB after stroke. Our treatment has demonstrated remarkable efficacy in enhancing bladder and kidney function, improving the overall quality of life, and alleviating anxiety and depression symptoms in this patient. This case study concludes that the noninvasive neuromodulation approach exhibits significant potential in the clinical field when addressing this specific patient population.

High-throughput single-cell mass spectrometry enables metabolic network analysis by resolving phospholipid C[double bond, length as m-dash]C isomers.

Single-cell mass spectrometry (MS) is an essential technology for sensitive and multiplexed analysis of metabolites and lipids for cell phenotyping and pathway studies. However, the structural elucidation of lipids from single cells remains a challenge, especially in the high-throughput scenario. Technically, there is a contradiction between the inadequate sample amount (i.e. a single cell, 0.5-20 pL) for replicate or multiple analysis, on the one hand, and the high metabolite coverage and multidimensional structure analysis that needs to be performed for each single cell, on the other hand. Here, we have developed a high-throughput single-cell MS platform that can perform both lipid profiling and lipid carbon-carbon double bond (C[double bond, length as m-dash]C) location isomer resolution analysis, aided by C[double bond, length as m-dash]C activation in unsaturated lipids by the Paternò-Büchi (PB) reaction and tandem MS, termed single-cell structural lipidomics analysis. The method can achieve a single-cell analysis throughput of 51 cells per minute. A total of 145 lipids were structurally characterized at the subclass level, of which the relative abundance of 17 isomeric lipids differing in the location of C[double bond, length as m-dash]C from 5 lipid precursors was determined. While cell-to-cell variations in MS1-based lipid profiling can be large, an advantage of quantifying lipid C[double bond, length as m-dash]C location isomers is the significantly improved quantitation accuracy. For example, the relative standard deviations (RSDs) of the relative amounts of PC 34:1 C[double bond, length as m-dash]C position isomers in MDA-MB-468 cells are half smaller than those measured for PC 34:1 as a whole by MS1 abundance profiling. Taken together, the developed method can be effectively used for in-depth structural lipid metabolism network analysis by high-throughput analysis of 142 MDA-MB-468 human breast cancer cells.

Extracellular Matrix Remodelling of the Periodontium under Orthodontic Force.

As the biological mechanisms of orthodontic tooth movement have been explored further, scholars have gradually focused on the remodelling mechanism of the extracellular matrix (ECM) in the periodontal ligament (PDL). The ECM of the PDL consists of various types of collagens and other glycoproteins. The specific process and mechanism of ECM remodelling during orthodontic tooth movement remains unclear. Collagen I and III, which constitute major components of the PDL, are upregulated under orthodontic force. The changes in the contents of ECM proteins also depend on the expression of ECM-related enzymes, which organise new collagen fibre networks to adapt to changes in tooth position. The matrix metalloproteinase family is the main enzyme that participates in collagen hydrolysis and renewal and changes its expression under orthodontic force. Moreover, ECM adhesion molecules, such as integrins, are also regulated by orthodontic force and participate in the dynamic reaction of cell adhesion and separation with the ECM. This article reviews the changes in ECM components, related enzymes and adhesion molecules in the PDL under orthodontic force to lay the foundation for the exploration of the regulatory mechanism of ECM remodelling during orthodontic tooth movement.