Quantitative CT analysis of idiopathic pulmonary fibrosis and correlation with lung function study.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a progressive fibrotic lung disease. However, the field of quantitative CT scan analysis in conjunction with pulmonary function test for IPF patients remains relatively understudied. In this study, we evaluated the diagnostic value of features derived high-resolution computed tomography (HRCT) for patients with IPF and correlated them with pulmonary function tests. METHODS: We retrospectively analyzed the chest HRCT images and pulmonary function test results of 52 patients with IPF during the same period (1 week) and selected 52 healthy individuals, matched for sex, age, and body mass index (BMI) and with normal chest HRCT as controls. HRCT scans were performed using a Philips 256-row Brilliance iCT scanner with standardized parameters. Lung function tests were performed using a Jaeger volumetric tracer for forced vital capacity (FVC), total lung capacity (TLC), forced expiratory volume in first second (FEV1), FEV1/FVC, carbon monoxide diffusing capacity (DLCO), and maximum ventilation volume (MVV) metrics. CT quantitative analysis, including tissue segmentation and threshold-based quantification of lung abnormalities, was performed using 3D-Slicer software to calculate the percentage of normal lung areas (NL%), percentage of ground-glass opacity areas (GGO%), percentage of fibrotic area (F%) and abnormal lesion area percentage (AA%). Semi-quantitative analyses were performed by two experienced radiologists to assess disease progression. The aortic-to-sternal distance (ASD) was measured on axial images as a standardized parameter. Spearman or Pearson correlation analysis and multivariate stepwise linear regression were used to analyze the relationship between the data in each group, and the ROC curve was used to determine the optimal quantitative CT metrics for identifying IPF and controls. RESULTS: ROC curve analysis showed that F% distinguished the IPF patient group from the control group with the largest area under the curve (AUC) of 0.962 (95% confidence interval: 0.85-0.96). Additionally, with F% = 4.05% as the threshold, the Youden's J statistic was 0.827, with a sensitivity of 92.3% and a specificity of 90.4%. The ASD was significantly lower in the late stage of progression than in the early stage (t = 5.691, P < 0.001), with a mean reduction of 2.45% per month. Quantitative CT indices correlated with all pulmonary function parameters except FEV1/FVC, with the highest correlation coefficients observed for F% and TLC%, FEV1%, FVC%, MVV% (r = - 0.571, - 0.520, - 0.521, - 0.555, respectively, all P-values < 0.001), and GGO% was significantly correlated with DLCO% (r = - 0.600, P < 0.001). Multiple stepwise linear regression analysis showed that F% was the best predictor of TLC%, FEV1%, FVC%, and MVV% (R2 = 0.301, 0.301, 0.300, and 0.302, respectively, all P-values < 0.001), and GGO% was the best predictor of DLCO% (R2 = 0.360, P < 0.001). CONCLUSIONS: Quantitative CT analysis can be used to diagnose IPF and assess lung function impairment. A decrease in the ASD may indicate disease progression.

Recent advances in the natural product analogues for the treatment of neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a hallmark of numerous incapacitating and untreatable conditions, the incidence of which is escalating swiftly, exemplified by Alzheimer's disease and Parkinson's disease. There is an urgent necessity to create pharmaceuticals that exhibit high efficacy and minimal toxicity in order to address these debilitating diseases. The structural complexity and diversity of natural products confer upon them a broad spectrum of biological activities, thereby significantly contributing to the history of drug discovery. Nevertheless, natural products present challenges in drug discovery, including time-consuming separation processes, low content, low bioavailability, and other related issues. To address these challenges, numerous analogs of natural products have been synthesized. This methodology enables the rapid synthesis of analogs of natural products with the potential to serve as lead compounds for drug development, thereby paving the way for the discovery of novel pharmaceuticals. This paper provides a summary of 127 synthetic analogues featuring various natural product structures, including flavonoids, alkaloids, coumarins, phenylpropanoids, terpenoids, polyphenols, and amides. The compounds are categorized based on their efficacy in treating various diseases. Furthermore, this article delves into the structure-activity relationship (SAR) of certain analogues, offering a thorough point of reference for the systematic development of pharmaceuticals aimed at addressing neurodegenerative conditions.

A Flexible and Optical Transparent Metasurface Absorber with Broadband RCS Reduction Characteristics.

Metasurface absorbers (MSAs) are of significant importance in a wide range of applications, such as in the field of stealth technology. Nevertheless, conventional designs demonstrate limited flexible characteristics and a lack of transparency, hence constraining their suitability for certain radar stealth applications. This study introduces a novel MSA operating in the broad microwave range, which exhibits both optical transparency and flexibility. The structure consists of a flexible substrate made of polyvinyl chloride (PVC), along with a resistive film composed of indium tin oxide (ITO). The proposed structure exhibits the ability to effectively absorb over 90% of the energy carried by incident electromagnetic (EM) waves across the frequency range of 9.85-41.76 GHz within an angular range of 0° to 60°. In addition, to assess the efficacy of the absorption performance, an examination of the radar cross-section (RCS) characteristics is conducted. The results indicate a reduction of over 10 dB across the aforementioned broad frequency spectrum, regardless of the central angle.

Lupiwighteone as an Antitumor Agent Reverses Multidrug Resistance in K562/ADR Cells by Regulating Cellular Prion Protein-Oct4 Axis.

INTRODUCTION: One of the many reasons for cancer treatment failure and recurrence is acquired Multidrug Resistance (MDR). Overcoming cancer drug resistance has been the focus of researchers' studies. Cellular prion protein (PrPC) is a glycophosphatidylinositol-anchored cell-surface glycoprotein that has been implicated in tumor behavior, including proliferation, apoptosis, invasion, metastasis, and chemoresistance. >Method: Lupiwighteone (Lup), a natural isoflavone found in the root of Glycyrrhiza glabra, has anticancer activity against prostate cancer cells, neuroblastoma cells, and human breast cancer cells. However, its pharmacological effects and mechanisms in drug-resistant cancer cells have not been reported. In this study, we used an adriamycin- resistant leukemia K562 cell model, and for the first time, we investigated the reversal effect of Lup on its MDR and the potential mechanism. RESULT: The results indicated that Lup could induce apoptosis through the mitochondrial pathway while upregulating the expression of related apoptotic proteins, such as Bax, Cyto C, Caspase-3, and PARP1. Autophagy is commonly recognized as a protective mechanism that mediates MDR during treatment. We found that Lup induced cellular autophagy while upregulating the expression of related autophagy proteins such as Beclin 1 and LC3 II. CONCLUSION: In addition, when Lup was combined with adriamycin, Lup decreased the IC50 of K562/ADR cells; moreover, Lup can downregulate the expression of drug-resistant proteins, suggesting that Lup can reverse drug resistance. Further studies have shown that Lup can downregulate the expression of PrPC-PI3K-Akt axis proteins and PrPC-Oct4 axis proteins. This study demonstrated that Lup has the potential to inhibit the proliferation of K562/ADR cells by targeting PrPC, and further study of the signaling pathway associated with PrPC may provide the experimental basis for the treatment of drug-resistant leukemia.

Transcutaneous Auricular Vagus Stimulation Attenuates LPS-Induced Depression-Like Behavior by Regulating Central α7nAChR/JAK2 Signaling.

Depression is a serious disabling disease worldwide. Accumulating evidence supports that there is a close relationship between depression and inflammation, and then inhibition of neuroinflammation may be another mechanism for the treatment of depression. Transcutaneous auricular vagus stimulation (taVNS), as a noninvasive transcutaneous electrical stimulation, could effectively treat depression, but its mechanism is unclear. In this study, rats with depression-like behavior were induced by intraperitoneal injection of lipopolysaccharide (LPS). The rats were randomly divided to control group, LPS group, taVNS + LPS group, and the same as the α7 nicotinic acetylcholine chloride receptor (α7nAChR) (- / -) gene knockout rats. The expressions of tumor necrosis factor alpha (TNF-ɑ) and phosphorylated-Janus kinase2 (p-JAK2), phosphorylated-signal transducer and activator of transcription3(p-STAT3) in the hypothalamus, amygdala, and hippocampus were detected by Western blot. We observed that LPS significantly decreased the sucrose preference, the time of into the open arms in the elevated plus maze, and the number of crossing and reaping in the open field test. TaVNS treatment improves these depression-like behaviors, but taVNS is not effective in α7nAChR (- / -) gene knockout rats. The expression of TNF-ɑ significantly increased, and the expression of p-Jak2 and p-STAT3 markedly decreased in the hypothalamus and amygdala induced by LPS. TaVNS could significantly reverse the abovementioned phenomena but had rare improvement effect for α7nAChR (- / -) rats. We conclude that the antidepressant effect of taVNS for LPS-induced depressive rats is related to α7nAchR/JAK2 signal pathway in the hypothalamus and amygdala.

Effect of Cerium on Inclusion Evolution and Pitting Corrosion of Nb-Microalloyed Steel.

Nb-microalloyed steels are widely used in construction engineering fields due to their excellent mechanical properties, but they face serious corrosion problems in service environments. Pitting corrosion is the severest form of corrosion, and the types of inclusions are the leading cause to induce pitting corrosion. A new strategy is proposed to enhance the corrosion resistance of steels by achieving a beneficial transformation of inclusions with Ce treatment. In this paper, two types of Nb-microalloyed steels (0% Ce and 0.0058% Ce steel) were prepared to study the modification effect on inclusions in industrial production. The spherical CaS•C12A7 inclusions were modified to smaller ellipsoidal Ce2O2S inclusions, and the proportion of inclusions (0-2 µm) increased significantly from 27 to 66%, while large inclusions (>6 µm) disappeared. A kinetic model of inclusion evolution was established. The results of electrochemical tests indicated that the corrosion potential was positively shifted, and the corrosion current was reduced after Ce treatment. Additionally, the number of defects in the passivation film was decreased, and the corrosion resistance of the steel was significantly improved. The addition of Ce changed the types of inclusions and reduced the number of pitting nucleation points, which led to a remarkable reduction in the number and size of pitting pits. The mechanism of pitting corrosion induced by different types of inclusions was further investigated, and a pitting corrosion model was modeled based on the immersion experiments. Research results provide theoretical support for enhancing the corrosion resistance of steel.

Degradation Behavior of Medical MgZZC-1 in Various Simulated Body Fluids.

Magnesium-based biodegradable metal bone implants exhibit superior mechanical properties compared to biodegradable polymers for orthopedic and cardiovascular stents. In this study, MgZZC-x (x = 1, 1.2) alloys were screened by in vitro biocompatibility tests in three simulated body fluids under nontoxic conditions. The MgZZC-1 alloys with better biocompatibility were selected to predict the days required for complete degradation. The evolution of degradation products was analyzed, and the mechanism of formation of the product film was inferred. A degradation kinetic model was established to investigate the effect of MEM components on the degradation of the alloys. The results demonstrate that the proteins in MEM can greatly retard the degradation progress by attaching to the surface of MgZZC-1 alloys, which are predicted to degrade completely within 341 days. The carbonate and phosphate buffers were adjusted to pH in MEM solution, delaying the degradation of magnesium alloys. This process in MEM more accurately reflects the actual degradation in the body and is superior to that in Hanks and SBF solutions. This study will promote the application of biodegradable materials in clinical medicine.

[Thinking of the treatment for lumbar spinal stenosis with high-dense silven needle therapy based on the theory of six-meridian differentiation].

The paper introduces the thinking of the diagnosis and treatment with high-dense silver needle therapy for lumbar spinal stenosis (LSS) based on the theory of six-meridian differentiation. According to the severity of LSS and the depth of illness location, LSS is differentiated as six syndromes/patterns, including taiyang disorder, yangming disorder, shaoyang disorder, shaoyin disorder, jueyin disorder and taiyin disorder. The high-dense silver needle therapy is used. The main points include the bilateral Jiaji points (EX-B 2) from L1 to L5 and the acupoints of the bladder meridian of foot-taiyang (1.5 cun lateral to each side of L1 to L5); and the supplementary points are selected from the affected meridians. According to the disorders of six meridians, the length of moxa stick is adjusted in warm acupuncture, targeting the tender sites of soft tissue damage. In order to obtain the satisfactory effects, the appropriate physical exercise is applicable rather than absolutely limiting the movement of affected vertebrae during the treatment.

Establishing stable and highly osteogenic hiPSC-derived MSCs for 3D-printed bone graft through microenvironment modulation by CHIR99021-treated osteocytes.

Human induced pluripotent stem cell (hiPSC)-derived mesenchymal stem cells (iMSCs) are ideal candidates for the production of standardised and scalable bioengineered bone grafts. However, stable induction and osteogenic differentiation of iMSCs pose challenges in the industry. We developed a precise differentiation method to produce homogeneous and fully differentiated iMSCs. In this study, we established a standardised system to prepare iMSCs with increased osteogenic potential and improved bioactivity by introducing a CHIR99021 (C91)-treated osteogenic microenvironment (COOME). COOME enhances the osteogenic differentiation and mineralisation of iMSCs via canonical Wnt signalling. Global transcriptome analysis and co-culturing experiments indicated that COOME increased the pro-angiogenesis/neurogenesis activity of iMSCs. The superior osteogenic differentiation and mineralisation abilities of COOME-treated iMSCs were also confirmed in a Bio3D module generated using a polycaprolactone (PCL) and cell-integrated 3D printing (PCI3D) system, which is the closest model to in vivo research. This COOME-treated iMSCs differentiation system offers a new perspective for generating highly osteogenic, bioactive, and anatomically matched grafts for clinical applications. Statement of significance: Although human induced pluripotent stem cell-derived MSCs (iMSCs) are ideal seed cells for synthetic bone implants, the challenges of stable induction and osteogenic differentiation hinder their clinical application. This study established a standardised system for the scalable preparation of iMSCs with improved osteogenic potential by combining our precise iMSC differentiation method with the CHIR99021 (C91)-treated osteocyte osteogenic microenvironment (COOME) through the activation of canonical Wnt signalling. Moreover, COOME upregulated the pro-angiogenic and pro-neurogenic capacities of iMSCs, which are crucial for the integration of implanted bone grafts. The superior osteogenic ability of COOME-treated iMSCs was confirmed in Bio3D modules generated using PCL and cell-integrated 3D printing systems, highlighting their functional potential in vivo. This study contributes to tissue engineering by providing insights into the functional differentiation of iMSCs for bone regeneration.

RP11-874 J12.4 promotes erlotinib resistance in non-small cell lung cancer via increasing AXL expression.

EGFR tyrosine kinase inhibitor (TKI) resistance is a major challenge for EGFR-mutant non-small cell lung cancer (NSCLC) treatment. Our previous work revealed that overexpression of AXL promoted EGFR-TKI resistance through epithelial-mesenchymal transition (EMT) in a subset of NSCLC patients. Compared with erlotinib resistant and sensitive cells, RP11-874 J12.4 was upregulated in erlotinib-resistant NSCLC cells (HCC827-ER3). Interestingly, the expression of RP11-874 J12.4 positively correlated with AXL. Besides, RP11-874 J12.4 promotes NSCLC cell proliferation and metastasis in vitro. Mechanistically, RP11-874 J12.4 promoted AXL expression through sponge with miR-34a-5p, which was reported to inhibit the translation of AXL mRNA. Meanwhile, the expression of RP11-874 J12.4 in lung cancer tumors were higher than the adjacent tissue, and those patients with high expression of RP11-874 J12.4 showed a poor prognosis in clinical. High expression of RP11-874 J12.4 might be a biomarker for NSCLC patients with erlotinib resistance. These findings reveal a novel insight into the mechanism of erlotinib resistance in NSCLC, and it might be a promising target for the diagnosis and treatment of NSCLC.

Pseudotargeted lipidomics analysis of scoparone on glycerophospholipid metabolism in non-alcoholic steatohepatitis mice by LC-MRM-MS.

As the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), the progression of nonalcoholic steatohepatitis (NASH) is associated with disorders of glycerophospholipid metabolism. Scoparone is the major bioactive component in Artemisia capillaris which has been widely used to treat NASH in traditional Chinese medicine. However, the underlying mechanisms of scoparone against NASH are not yet fully understood, which hinders the development of effective therapeutic agents for NASH. Given the crucial role of glycerophospholipid metabolism in NASH progression, this study aimed to characterize the differential expression of glycerophospholipids that is responsible for scoparone's pharmacological effects and assess its efficacy against NASH. Liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) was performed to get the concentrations of glycerophospholipids, clarify mechanisms of disease, and highlight insights into drug discovery. Additionally, pathologic findings also presented consistent changes in high-fat diet-induced NASH model, and after scoparone treatment, both the levels of glycerophospholipids and histopathology were similar to normal levels, indicating a beneficial effect during the observation time. Altogether, these results refined the insights on the mechanisms of scoparone against NASH and suggested a route to relieve NASH with glycerophospholipid metabolism. In addition, the current work demonstrated that a pseudotargeted lipidomic platform provided a novel insight into the potential mechanism of scoparone action.

Bioengineered Artificial Extracellular Vesicles Presenting PD-L1 and Gal-9 Ameliorate New-Onset Type 1 Diabetes.

An important factor in the development of type 1 diabetes (T1D) is the deficiency of inhibitory immune checkpoint ligands, specifically programmed cell death ligand 1 (PD-L1) and galectin-9 (Gal-9), in ß-cells. Therefore, modulation of pancreas-infiltrated T lymphocytes by exogenous PD-L1 or Gal-9 is an ideal approach for treating new-onset T1D. We genetically engineered macrophage cells to generate artificial extracellular vesicles (aEVs) overexpressing PD-L1 and Gal-9, which could restrict islet autoreactive T lymphocytes and protect ß-cells from destruction. Intriguingly, overexpression of Gal-9 stimulated macrophage polarization to the M2 phenotype with immunosuppressive attributes. Alternatively, both PD-L1- and Gal-9-presenting aEVs (PD-L1-Gal-9 aEVs) favorably adhered to T cells via the interaction of programmed cell death protein 1/PD-L1 or T-cell immunoglobulin mucin 3/Gal-9. Moreover, PD-L1-Gal-9 aEVs prominently promoted effector T-cell apoptosis and splenic regulatory T (Treg) cell formation in vitro. Notably, PD-L1-Gal-9 aEVs efficaciously reversed new-onset hyperglycemia in NOD mice, prevented T1D progression, and decreased the proportion and activation of CD4+ and CD8+ T cells infiltrating the pancreas, which together contributed to the preservation of residual ß-cell survival and mitigation of hyperglycemia.

IDN5706 Inhibits Synovial Inflammation via Inducing M2 Polarization of Synovial Macrophages in Osteoarthritis Rats.

INTRODUCTION: IDN5706 is a tetrahydro derivative of hyperforin. In this study, we aimed to explore the effect of IDN5706 on synovial macrophages in osteoarthritis (OA) rats and the underlying mechanisms. METHODS: OA rats were employed for the in vivo experiments, and RAW264.7 cells were employed for the in vitro experiments. Histopathological changes in synovium were examined using hematoxylin-eosin staining. Cell apoptosis in synovium was assessed by TUNEL staining. Macrophage polarization was determined by immunohistochemical analysis and flow cytometry. The mRNA expression and protein level of genes were detected by qRT-PCR and Western blot. The efferocytosis of macrophages was assessed by flow cytometry. RESULTS: IDN5706 reversed the increased CD86-positive cells (M1 macrophages) and decreased CD206-positive cells (M2 macrophages), both in synovium and synovial fluid of OA rats. The in vitro experiments further confirmed the promotion effect of IDN5706 on M2 macrophages, accompanied by the elevated Arg-1 and reduced iNOS. Also, the upregulated p-mTOR in synovium and synovial fluid of OA rats were reversed by IDN5706, and the decreased M1 macrophages and increased M2 macrophages induced by IDN5706 were reversed by the mTOR activator. IDN5706 enhanced the efferocytosis of IL-4-treated RAW264.7 cells, and the animal experiments further revealed the involvement of efferocytosis in the improvement of OA by IDN5706. CONCLUSIONS: IDN5706 enhanced the efferocytosis of synovial macrophages by inducing M2 polarization via inhibiting p-mTOR, thus suppressing synovial inflammation and OA development, providing a theoretical basis for IDN5706 as a clinical drug for inflammatory diseases.

Study on the Preparation and Process Parameter-Mechanical Property Relationships of Carbon Fiber Fabric Reinforced Poly(Ether Ether Ketone) Thermoplastic Composites.

Carbon fiber fabric-reinforced poly(ether ether ketone) (CFF-PEEK) composites exhibit exceptional mechanical properties, and their flexibility and conformability make them a promising alternative to traditional prepregs. However, the formation of the CFF-PEEK composite is trapped in the high viscosity of PEEK, the smooth surface, and tightly interwoven bundles of CFF. It is more difficult for the resin to flow through the fibers of complex textile structures. Here, a simple film stacking method using the hot-pressing process of plain-woven CFF-PEEK thermoplastic composites is discussed. The uniform distribution of PEEK resin between each layer of CFF reduces the flow distance during the molding process, preventing defects in the composite material effectively. Four process parameters, including molding temperature (370, 385, 400, and 415 °C), molding pressure (1, 2, 4, 8, and 10 MPa), molding time (10, 20, 30, 40, 60, and 90 min), and pre-compaction process, are considered. Interlaminar shear strength (ILSS), tensile strength, and flexural strength of CFF/PEEK composites are evaluated to optimize the process parameters. Moreover, ultrasonic scanning microscopy and scanning electron microscopy are employed to observe the formation quality and microscopic failure modes of CFF/PEEK composites, respectively. The ultimate process parameters are a molding temperature of 410 °C, molding pressure of 10 MPa, molding time of 60 min, and the need for the pre-compaction process. Under the best process parameters, the ILSS is 62.5 MPa, the flexural strength is 754.4 MPa, and the tensile strength is 796.1 MPa. This work provides valuable insight for studying the process parameters of fiber fabric-reinforced thermoplastic polymer composites and revealing their impact on mechanical properties.

Preparation of Superhydrophobic Coating on X80 Steel and Its Corrosion Resistance in Oilfield Produced Water.

Corrosion is an unavoidable issue that steel encounters during service; however, the generic methods employed for corrosion prevention often need high cost or preparation conditions. In this study, a facile chemical replacement deposition method was proposed to realize an anticorrosion superhydrophobic coating on a X80 steel surface. The growth mechanism of the rough structure and its impact on the wettability of the superhydrophobic coating were analyzed. The superhydrophobic coating, deposited for 50 s and modified for 30 min, achieved optimal electrochemical properties and a maximum water contact angle. The immersion test, in the saturated CO2 oilfield produced water, demonstrated the better corrosion resistance of superhydrophobic coating than X80 steel. Correspondingly, a kinetic corrosion model was established to analyze the anticorrosion mechanism. In summary, this method significantly improves the corrosion resistance of X80 steel and is attractive for other industrial fields.

Silk Fibroin Formed Bioadhesive Ophthalmic Gel for Dry Eye Syndrome Treatment.

PURPOSE: Dry eye syndrome (DES), arising from various etiologic factors, leads to tear film instability and ocular surface damage. Given its anti-inflammatory effects, cyclosporine A (CsA) has been widely used as a short-term treatment option for DES. However, poor bioavailability and solubility of CsA in aqueous phase make the development of a cyclosporine A-based eye drop for ocular topical application a huge challenge. METHODS: In this study, a novel strategy for preparing cyclosporine A-loaded silk fibroin nanoemulsion gel (CsA NBGs) was proposed to address these barriers. Additionally, the rheological properties, ocular irritation potential, tear elimination kinetics, and pharmacodynamics based on a rabbit dry eye model were investigated for the prepared CsA NBGs. Furthermore, the transcorneal mechanism across the ocular barrier was also investigated. RESULTS: The pharmacodynamics and pharmacokinetics of CsA NBGs exhibited superior performance compared to cyclosporine eye drops, leading to a significant enhancement in the bioavailability of CsA NBGs. Furthermore, our investigation into the transcorneal mechanism of CsA NBGs revealed their ability to be absorbed by corneal epithelial cells via the paracellular pathway. CONCLUSION: The CsA NBG formulation exhibits promising potential for intraocular drug delivery, enabling safe, effective, and controlled administration of hydrophobic drugs into the eye. Moreover, it enhances drug retention within the ocular tissues and improves systemic bioavailability, thereby demonstrating significant clinical translational prospects.

Electroacupuncture regulates gut microbiota to reduce depressive-like behavior in rats.

Background and objectives: Growing studies show that gut microbiota is closely associated with depression. Acupuncture treatment could regulate the gut microbiota of many diseases. Here, we aim to observe the effect of electroacupuncture (EA) on gut microbiota in rats that showed depressive-like behavior. Materials and methods: The rats were randomly divided into normal group, chronic unpredictable mild stress model (CUMS) group, CUMS + electroacupuncture (EA) group, and CUMS + sham-electroacupuncture (Sham) group. The CUMS+EA rats were treated with EA stimulation at bilateral Zusanli (ST36) and Tianshu (ST25) acupoints for 2 weeks (0.7 mA, 2/100 Hz, 30 min/day). The rats in the sham EA group were treated with the same conditions without inserting needles and electrical stimulation. Behavioral tests were conducted by forced swimming test (FST), open field test (OFT), and sucrose preference test (SPT) to assess depression-like behavior in rats. The relative abundance of intestinal bacteria in rat feces was detected by 16S rRNA analysis. The expression of calcitonin-gene-related peptide (CGRP), vasoactive intestinal peptide (VIP), somatostatin (SST), and adrenocorticotropic hormone (ACTH) in serum was detected by ELISA kit, and VIP, CGRP, and SST in the colon were detected by qRT-PCR and Western blot. Results: Chronic unpredictable mild stress model rats exhibited depressive-like behaviors and had differential abundance vs. control rats. CUMS significantly decreased the relative abundance of Bifidobacterium and Streptococcus at the genus level, CGRP in plasma (p < 0.05), and significantly increased the intestine propulsion rate, the mRNA and protein expression of VIP, SST, and mRNA in the colon, and ATCH in plasma (p < 0.05). EA rats with microbial profiles were distinct from CUMS rats. EA markedly reduced the depressive-like behaviors, significantly increased the intestine propulsion rate, the relative abundance of Bacteroidetes, Proteobacteria, and Actinobacteria at the phylum level, Bifidobacterium and Streptococcus at the genus level, and VIP and CGRP in plasma (p < 0.05), and significantly decreased Firmicutes, the ratio of Firmicutes to Bacteroidetes at the phylum level, ACTH and SST in plasma, and SST mRNA in the colon (p < 0.05). Conclusion: The antidepressant effect of EA at ST36 and ST25 is related to regulating intestinal flora and the neurotransmitter system. Our study suggests that EA contributes to the improvement of depression, and gut microbiota may be one of the mechanisms of EA effect.

The Osteocyte with SB216763-Activated Canonical Wnt Signaling Constructs a Multifunctional 4D Intelligent Osteogenic Module.

The enhancement of bioactivity in materials has become an important focus within the field of bone tissue engineering. Four-dimensional intelligent osteogenic module, an innovative fusion of 3D printing with the time axis, shows immense potential in augmenting the bioactivity of these materials, thereby facilitating autologous bone regeneration efficiently. This study focuses on novel bone repair materials, particularly bioactive scaffolds with a developmental osteogenic microenvironment prepared through 3D bioprinting technology. This research mainly creates a developmental osteogenic microenvironment named "DOME". This is primed by the application of a small amount of the small molecule drug SB216763, which activates canonical Wnt signaling in osteocytes, promoting osteogenesis and mineralization nodule formation in bone marrow stromal cells and inhibiting the formation of adipocytes. Moreover, DOME enhances endothelial cell migration and angiogenesis, which is integral to bone repair. More importantly, the DOME-PCI3D system, a 4D intelligent osteogenic module constructed through 3D bioprinting, stably supports cell growth (91.2% survival rate after 7 days) and significantly increases the expression of osteogenic transcription factors in bone marrow stromal cells and induces osteogenic differentiation and mineralization for 28 days. This study presents a novel approach for bone repair, employing 3D bioprinting to create a multifunctional 4D intelligent osteogenic module. This innovative method not only resolves challenges related to shape-matching and biological activity but also demonstrates the vast potential for applications in bone repair.

Deep learning-based automatic segmentation of meningioma from T1-weighted contrast-enhanced MRI for preoperative meningioma differentiation using radiomic features.

BACKGROUND: This study aimed to establish a dedicated deep-learning model (DLM) on routine magnetic resonance imaging (MRI) data to investigate DLM performance in automated detection and segmentation of meningiomas in comparison to manual segmentations. Another purpose of our work was to develop a radiomics model based on the radiomics features extracted from automatic segmentation to differentiate low- and high-grade meningiomas before surgery. MATERIALS: A total of 326 patients with pathologically confirmed meningiomas were enrolled. Samples were randomly split with a 6:2:2 ratio to the training set, validation set, and test set. Volumetric regions of interest (VOIs) were manually drawn on each slice using the ITK-SNAP software. An automatic segmentation model based on SegResNet was developed for the meningioma segmentation. Segmentation performance was evaluated by dice coefficient and 95% Hausdorff distance. Intra class correlation (ICC) analysis was applied to assess the agreement between radiomic features from manual and automatic segmentations. Radiomics features derived from automatic segmentation were extracted by pyradiomics. After feature selection, a model for meningiomas grading was built. RESULTS: The DLM detected meningiomas in all cases. For automatic segmentation, the mean dice coefficient and 95% Hausdorff distance were 0.881 (95% CI: 0.851-0.981) and 2.016 (95% CI:1.439-3.158) in the test set, respectively. Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). Features extracted on manual and automatic segmentation are comparable: the average ICC value was 0.804 (range, 0.636-0.933). For meningioma classification, the radiomics model based on automatic segmentation performed well in grading meningiomas, yielding a sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.778 (95% CI: 0.701-0.856), 0.860 (95% CI: 0.722-0.908), 0.848 (95% CI: 0.715-0.903) and 0.842 (95% CI: 0.807-0.895) in the test set, respectively. CONCLUSIONS: The DLM yielded favorable automated detection and segmentation of meningioma and can help deploy radiomics for preoperative meningioma differentiation in clinical practice.