A retrospective study on the correction of distal arthrogryposis with a progressive extension brace.

Purpose: Camptodactyly, clasped thumbs, and windblown hands are distinctive features of distal arthrogryposis (DA). Current therapeutic interventions often yield suboptimal effects, predisposing patients to relapses and complications. This study explicates a corrective approach involving a progressive extension brace for the management of DA and evaluates its clinical outcomes. Methods: Between 2015 and 2023, progressive extension braces were used in 32 DA patients, with an average follow-up of 4.8 years. Patients were stratified by age into four groups: 0-1, 1-3, 3-7, and above 7 years. The correction of camptodactyly was assessed based on the total active movement (TAM) of metacarpophalangeal joints (MPJ) and proximal interphalangeal joints (PIPJ), as well as the extensor lag of PIPJ. Clasped thumb correction was evaluated by measuring the thumb-to-index finger metacarpal angle (M1M2 angle) and the degree of deviation at the first MPJ (M1P1 angle). The quality of life for the children was measured using PedsQL 4.0, while parental satisfaction was gauged using the FACE questionnaire. Results: Earlier intervention with a progressive extension brace yielded superior corrective results. Infants aged 0-1 year and toddlers aged 1-3 years achieved average TAM scores of 152° and 126° after correction; however, patients older than 3 years experienced a significant decrease in TAM with the same treatment. Infants and toddlers with DA showed improvement in the average extensor lag from 46° to 6°. The M1M2 angle increased from an average of 38° to 65°, with the M1P1 angle decreasing from an average of 43° to 5°. After the treatment, average PedsQL scores of 94.7 (parent-reported) and 89.3 (child-reported) were achieved. Among the 32 parents, 24 expressed high satisfaction, 5 expressed moderate satisfaction, and 3 expressed fair satisfaction. Conclusion: The early, progressive, and consistent use of an extension brace significantly improved joint mobility and corrected camptodactyly and clasped thumbs. It can be an effective approach to addressing hand deformities in patients with DA.

The impact of 5-aminosalicylates on the efficacy of mesenchymal stem cell therapy in a murine model of ulcerative colitis.

Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.

Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy.

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4+ and CD8+ T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Experimental test and mechanism analysis of soil crust erosion resistance of rammed earth Great Wall in rainy season.

Rammed earth is a kind of cleaning material, widely used in all kinds of buildings in the world. The Great Wall of ancient China is a typical world cultural site built from rammed earth. The rammed earth Great Wall of Shanhaiguan is close to Bohai Bay, which has suffered from long-term erosion by rain, causing a series of problems such as soil loss, collapse and gully flushing. The protection materials of the rammed earth site have always puzzled scholars. However, during the rainy season, it was found that some of the walls at Xiaowan Gouge and Nantuzhuang Gouge in the Shanhaiguan Great Wall had unwashed traces, the soil surface of the walls was intact, and the anti-erosion ability of the walls was significantly higher than that of other places. In order to explore the reasons for its strong anti-erosion ability in the natural state of rammed earth wall, guide the protection of rammed earth Great Wall, and carry out different experimental tests to explore its anti-erosion reasons and internal mechanisms. Firstly, the characteristics of rammed soil were understood through the composition test of rammed soil, and the indoor and outdoor erosion test was carried out to determine that the anti-erosion reason was the protection of gray-green soil crust. The property and composition of soil crust were determined through the immersion test and genome sequencing. Finally, the protection mechanism of soil crust was analyzed by scanning electron microscopy.

Preparation of Puerarin Long Circulating Liposomes and its Effect on Osteoporosis in Castrated Rats.

Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/ß-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59 nm and -25.54±0.11 mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, ß-catenin and T-cell factor (TCF) expressions at protein level in the wnt/ß-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis.

Comprehensive Overview of Treponema pallidum Outer Membrane Proteins.

Treponema pallidum, the causative agent of syphilis, is a sexually transmitted microorganism that exhibits remarkable motility capabilities, allowing it to affect various systems. Despite its structural resemblance to gram-negative bacteria due to its dual-membrane, T. pallidum possesses a lower abundance of outer membrane proteins (OMPs), which enables it to effectively conceal itself. This review presents a comprehensive analysis of the clinical diagnostic potential associated with the OMPs of T. pallidum. Furthermore, the known OMPs in T. pallidum that are responsible for mediating host interactions have been progressively elucidated. This review aims to shed light on the pathogenesis of syphilis, encompassing aspects such as vascular inflammation, chancre self-healing, neuroinvasion, and reinfection. Additionally, this review offers a detailed overview of the current state and prospects of development in the field of syphilis vaccines, with the ultimate goal of establishing a foundation for understanding the pathogenesis and implementing effective prevention strategies against syphilis.

EgMADS3 directly regulates EgLPAAT to mediate medium-chain fatty acids (MCFA) anabolism in the mesocarp of oil palm.

KEY MESSAGE: EgMADS3, a pivotal transcription factor, positively regulates MCFA accumulation via binding to the EgLPAAT promoter, advancing lipid content in mesocarp of oil palm. Lipids function as the structural components of cell membranes, which serve as permeable barriers to the external environment of cells. The medium-chain fatty acid in the stored lipids of plants is an important renewable energy. Most research on MCFA production in plant lipid synthesis is based on biochemical methods, and the importance of transcriptional regulation in MCFA synthesis and its incorporation into TAGs needs further research. Oil palm is the most productive oil crop in the world and has the highest productivity among the main oil crops. In this study, the MADS transcription factor (EgMADS3) in the mesocarp of oil palm was characterized. Through the VIGS-virus induced gene silencing, it was determined that the potential target gene of EgMADS3 was related to the biosynthesis of medium-chain fatty acid (MCFA). Transient transformation in protoplasts and qRT-PCR analysis showed that EgMADS3 positively regulated the expression of EgLPAAT. The results of the yeast one-hybrid assays and EMSA indicated the interaction between EgMADS3 and EgLPAAT promoter. Through genetic transformation and fatty acid analysis, it is concluded that EgMADS3 directly regulates the mid-chain fatty acid synthesis pathway of the potential target gene EgLPAAT, thus promotes the accumulation of MCFA and improves the total lipid content. This study is innovative in the functional analysis of the MADS family transcription factor in the metabolism of medium-chain fatty acids (MCFA) of oil palm, provides a certain research basis for improving the metabolic pathway of chain fatty acids in oil palm, and improves the synthesis of MCFA in plants. Our results will provide a reference direction for further research on improving the oil quality through biotechnology of oil palm.

Using Claims Data to Predict Pre-Operative BMI Among Bariatric Surgery Patients: Development of the BMI Before Bariatric Surgery Scoring System (B3S3).

Background: Lack of body mass index (BMI) measurements limits the utility of claims data for bariatric surgery research, but pre-operative BMI may be imputed due to existence of weight-related diagnosis codes and BMI-related reimbursement requirements. We used a machine learning pipeline to create a claims-based scoring system to predict pre-operative BMI, as documented in the electronic health record (EHR), among patients undergoing a new bariatric surgery. Methods: Using the Optum Labs Data Warehouse, containing linked de-identified claims and EHR data for commercial or Medicare Advantage enrollees, we identified adults undergoing a new bariatric surgery between January 2011 and June 2018 with a BMI measurement in linked EHR data ≤30 days before the index surgery (n=3226). We constructed predictors from claims data and applied a machine learning pipeline to create a scoring system for pre-operative BMI, the B3S3. We evaluated the B3S3 and a simple linear regression model (benchmark) in test patients whose index surgery occurred concurrent (2011-2017) or prospective (2018) to the training data. Results: The machine learning pipeline yielded a final scoring system that included weight-related diagnosis codes, age, and number of days hospitalized and distinct drugs dispensed in the past 6 months. In concurrent test data, the B3S3 had excellent performance (R2 0.862, 95% confidence interval [CI] 0.815-0.898) and calibration. The benchmark algorithm had good performance (R2 0.750, 95% CI 0.686-0.799) and calibration but both aspects were inferior to the B3S3. Findings in prospective test data were similar. Conclusion: The B3S3 is an accessible tool that researchers can use with claims data to obtain granular and accurate predicted values of pre-operative BMI, which may enhance confounding control and investigation of effect modification by baseline obesity levels in bariatric surgery studies utilizing claims data.

Pre-operative BMI is an important potential confounder in comparative effectiveness studies of bariatric surgeries.Claims data lack clinical measurements, but insurance reimbursement requirements for bariatric surgery often result in pre-operative BMI being coded in claims data.We used a machine learning pipeline to create a model, the B3S3, to predict pre-operative BMI, as documented in the EHR, among bariatric surgery patients based on the presence of certain weight-related diagnosis codes and other patient characteristics derived from claims data.Researchers can easily use the B3S3 with claims data to obtain granular and accurate predicted values of pre-operative BMI among bariatric surgery patients.

Hereditary hemochromatosis caused by a C282Y/H63D mutation in the HFE gene: A case report.

Hereditary hemochromatosis (HH) is a disease characterized by disordered iron metabolism. It often involves mutations of the HFE gene, which encodes the homeostatic iron regulator protein (HFE), as well as mutations affecting hepcidin antimicrobial peptide, hemojuvelin, or transferrin receptor 2. Historically, HH has been observed primarily in European and European diaspora populations, while classical HH is rare in Asian populations, including in China. In this article, we report a rare case of HH in a Chinese man that could be attributed to a heterozygous C282Y/H63D HFE mutation. Based on clinical examination, liver biopsy, and genetic testing results, the patient was diagnosed with HH. Clinical signs and symptoms and serum iron-related test results were recorded for a period of two years after the patient began treatment. Over this observation period, the patient was subjected to 25 phlebotomies (accounting for a total blood loss of 10.2 L). His serum ferritin levels decreased from 1550 µg/L to 454 µg/L, his serum iron concentration decreased from 40 µmol/L to 24.6 µmol/L, and his transferrin saturation decreased from 97.5% to 55.1%. Early diagnosis is essential for patients with HH to obtain good outcomes. Regular phlebotomy after diagnosis can improve HH symptoms and delay HH disease progression.

An Investigation of the Efficient-Precise Continuous Electrochemical Grinding Process of Ti-6Al-4V.

Titanium alloys have many excellent characteristics, and they are widely used in aerospace, biomedicine, and precision engineering. Meanwhile, titanium alloys are difficult to machine and passivate readily. Electrochemical grinding (ECG) is an ideal technology for the efficient-precise machining of titanium alloys. In the ECG process of titanium alloys, the common approach of applying high voltage and active electrolytes to achieve high efficiency of material removal will lead to serious stray corrosion, and the time utilized for the subsequent finishing will be extended greatly. Therefore, the application of ECG in the field of high efficiency and precision machining of titanium alloys is limited. In order to address the aforementioned issues, the present study proposed an efficient-precise continuous ECG (E-P-C-ECG) process for Ti-6Al-4V applying high-pulsed voltage with an optimized duty cycle and low DC voltage in the efficient ECG stage and precise ECG stage, respectively, without changing the grinding wheel. According to the result of the passivation properties tests, the ideal electrolyte was selected. Optimization of the process parameters was implemented experimentally to improve the processing efficiency and precision of ECG of Ti-6Al-4V. Utilizing the process advantages of the proposed process, a thin-walled structure of Ti-6Al-4V was obtained with high efficiency and precision. Compared to the conventional mechanical grinding process, the compressive residual stress of the machined surface and the processing time were reduced by 90.5% and 63.3% respectively, and both the surface roughness and tool wear were obviously improved.

Meta-Quantitative Trait Loci Analysis and Candidate Gene Mining for Drought Tolerance-Associated Traits in Maize (Zea mays L.).

Drought is one of the major abiotic stresses with a severe negative impact on maize production globally. Understanding the genetic architecture of drought tolerance in maize is a crucial step towards the breeding of drought-tolerant varieties and a targeted exploitation of genetic resources. In this study, 511 quantitative trait loci (QTL) related to grain yield components, flowering time, and plant morphology under drought conditions, as well as drought tolerance index were collected from 27 published studies and then projected on the IBM2 2008 Neighbors reference map for meta-analysis. In total, 83 meta-QTL (MQTL) associated with drought tolerance in maize were identified, of which 20 were determined as core MQTL. The average confidence interval of MQTL was strongly reduced compared to that of the previously published QTL. Nearly half of the MQTL were confirmed by co-localized marker-trait associations from genome-wide association studies. Based on the alignment of rice proteins related to drought tolerance, 63 orthologous genes were identified near the maize MQTL. Furthermore, 583 candidate genes were identified within the 20 core MQTL regions and maize-rice homologous genes. Based on KEGG analysis of candidate genes, plant hormone signaling pathways were found to be significantly enriched. The signaling pathways can have direct or indirect effects on drought tolerance and also interact with other pathways. In conclusion, this study provides novel insights into the genetic and molecular mechanisms of drought tolerance in maize towards a more targeted improvement of this important trait in breeding.

Fabricating Precise and Smooth Microgroove Structures on Zr-Based Metallic Glass Using Jet-ECM.

Zr-based metallic glasses (MGs) are promising materials for mold manufacturing due to their unique mechanical and chemical properties. However, the high hardness of metallic glasses and their tendency to crystallize at high temperatures make it challenging to fabricate precise and smooth microscale structures on metallic glasses. This limitation hampers the development of metallic glasses as molds. Jet electrochemical machining (jet-ECM) is a non-contact subtractive manufacturing technology that utilizes a high-speed electrolyte to partially remove material from workpieces, making it highly suitable for processing difficult-to-machine materials. Nevertheless, few studies have explored microgroove structures on Zr-based MGs using sodium nitrate electrolytes by jet-ECM. Therefore, this paper advocates the utilization of the jet-ECM technique to fabricate precise and smooth microgroove structures using a sodium nitrate electrolyte. The electrochemical characteristics were studied in sodium nitrate solution. Then, the effects of the applied voltages and nozzle travel rates on machining performance were investigated. Finally, micro-helical and micro-S structures with high geometric dimensional consistency and low surface roughness were successfully fabricated, with widths and depths measuring 433.7 ± 2.4 µm and 101.4 ± 1.6 µm, respectively. Their surface roughness was determined to be 0.118 ± 0.002 µm. Compared to non-aqueous-based methods for jet-ECM of Zr-based MGs, the depth of the microgrooves was increased from 20 µm to 101 µm. Furthermore, the processed microstructures had no uneven edges in the peripheral areas and no visible flow marks on the bottom.

Effects of C and Al Alloying on Constitutive Model Parameters and Hot Deformation Behavior of Medium-Mn Steels.

Single-pass isothermal hot compression tests on four medium-Mn steels with different C and Al contents were conducted using a Gleeble-3500 thermal simulation machine at varying deformation temperatures (900-1150 °C) and strain rates (0.01-5 s-1). Based on friction correction theory, the friction of the test stress-strain data was corrected. On this basis, the Arrhenius constitutive model of experimental steels considering Al content and strain compensation and hot processing maps of different experimental steels at a strain of 0.9 were established. Moreover, the effects of C and Al contents on constitutive model parameters and hot processing performance were analyzed. The results revealed that the increase in C content changed the trend of the thermal deformation activation energy Q with the true strain. The Q value of 2C7Mn3Al increased by about 50 KJ/mol compared with 7Mn3Al at a true strain greater than 0.4. In contrast, increasing the Al content from 0 to 1.14 wt.% decreased the activation energy of thermal deformation in the true strain range of 0.4-0.9. Continuing to increase to 3.30 wt.% increased the Q of 7Mn3Al over 7Mn by about 65 KJ/mol over the full strain range. In comparison, 7Mn1Al exhibited the best hot processing performance under the deformation temperature of 975-1125 °C and strain rate of 0.2-5 s-1. This is due to the addition of C element reduces the δ-ferrite volume fraction, which leads to the precipitation of κ-carbides and causes the formation of microcracks; an increase in Al content from 0 to 1.14 wt.% reduces the austenite stability and improves the hot workability, but a continued increase in the content up to 3.30 wt.% results in the emergence of δ-ferrite in the microstructure, which slows down the austenite DRX and not conducive to the hot processing performance.

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

Local-Global Geometric Information and View Complementarity Introduced Multiview Metric Learning.

Geometry studies the spatial structure and location information of objects, providing a priori knowledge and intuitive explanation for classification methods. Considering samples from a geometric perspective offers a novel approach to understanding their information. In this article, we propose a method called local-global geometric information and view complementarity introduced multiview metric learning (GIVCMML). Our method effectively exploits the geometric information of multiview samples. The learned metric space retains the geometric relations of samples and makes them more separable. First, we propose the global geometrical constraint in the maximum margin criterion framework. By maximizing the distance between class centers in the metric space, we ensure that samples from different classes are well separated. Second, to maintain the manifold structure of the original space, we build an adjacency matrix that contains the sample label information. This helps explore the local geometric information of sample pairs. Finally, to better mine the complementary information of multiview samples, GIVCMML maximizes the correlation between each view in the metric space. This enables each view to adaptively learn from the others and explore the complementary information between views. We extensively evaluate the effectiveness of our method on real-world datasets. The experimental results demonstrate that GIVCMML achieves competitive performance compared with multiview metric learning (MvML) methods.

Microfabricating Mirror-like Surface Precision Micro-Sized Amorphous Alloy Structures Using Jet-ECM Process.

Amorphous alloy (AA) is a high-performance metal material generally with significantly excellent mechanical and corrosion resistance properties and thus is considered as a desirable material selection for micro-scale articles. However, the microfabrication of AA still faces a variety of technical challenges mainly because the materials are too hard to process and easily lose their original properties, although at moderately high temperatures. In this study, jet-electrolyte electrochemical machining (Jet-ECM) was proposed to microfabricate the Zr-based AA because it is a low-temperature material-removal process based on the anode dissolution mechanism. The electrochemical dissolution characteristics and material removal mechanism of AA were investigated, and then the optimal process parameters were achieved based on the evaluation of the surface morphologies, surface roughness, geometrical profile, and machining accuracy of the machined micro-dimples. Finally, the feasibility was further studied by using Jet-ECM to fabricate arrayed micro-dimples using the optimized parameters. It was found that Jet-ECM can successfully microfabricate mirror-like surface AA arrayed precision micro-dimples with significantly high dimensional accuracy and geometrical consistency. Jet-ECM is a promisingly advantageous microfabrication process for the hard-to-machine AA.

Transcriptome analysis provides new insights into the immune response of Ruditapes philippinarum infected with Vibrio alginolyticus.

Manila clam (Ruditapes philippinarum) is a bivalve species with commercial value, but it is easily infected by pathogenic microorganisms in aquaculture, which restricts the shellfish industry. Notably, the impact of Vibrio alginolyticus on clam culture is obvious. In this study, RNA-seq was performed to analyze clam hepatopancreas tissue in 48 h (challenge group, G48h) and 96 h (challenge group, G96h) after infection with V. alginolyticus and 0 h after injection of PBS (control group, C). The results showed that a total of 1670 differentially expressed genes were detected in the G48h vs C group, and 1427 differentially expressed genes were detected in the G96h vs C group. In addition, KEGG analysis showed that DEGs were significantly enriched in pathways such as Lysosome and Mitophagy. Moreover, 15 immune related DEGs were selected for qRT-PCR analysis to verify the accuracy of RNA-seq, and the results showed that the expression level of DEGs was consistent with that of RNA-seq. Therefore, the results obtained in this study provides a preliminary understanding of the immune defense of R. philippinarum and molecular insights for genetic breeding of V. alginolyticus resistance in Manila clam.

Mitigating phospholipid peroxidation of macrophages in stress-induced tumor microenvironment by natural ALOX15/PEBP1 complex inhibitors.

BACKGROUND: The intricate interactions between chronic psychological stress and susceptibility to breast cancer have been recognized, yet the underlying mechanisms remain unexplored. Danzhi Xiaoyao Powder (DZXY), a traditional Chinese medicine (TCM) formula, has found clinical utility in the treatment of breast cancer. Macrophages, as the predominant immune cell population within the tumor microenvironment (TME), play a pivotal role in orchestrating tumor immunosurveillance. Emerging evidence suggests that lipid oxidation accumulation in TME macrophages, plays a critical role in breast cancer development and progression. However, a comprehensive understanding of the pharmacological mechanisms and active components of DZXY related to its clinical application in the treatment of stress-aggravated breast cancer remains elusive. PURPOSE: This study sought to explore the plausible regulatory mechanisms and identify the key active components of DZXY contributing to its therapeutic efficacy in the context of breast cancer. METHODS: Initially, we conducted an investigation into the relationship between the phagocytic capacity of macrophages damaged by psychological stress and phospholipid peroxidation using flow cytometry and LC-MS/MS-based phospholipomics. Subsequently, we evaluated the therapeutic efficacy of DZXY based on the results of the tumor size, tumor weight, the phospholipid peroxidation pathway and phagocytosis of macrophage. Additionally, the target-mediated characterization strategy based on binding of arachidonate 15-lipoxygenase (ALOX15) to phosphatidylethanolamine-binding protein-1 (PEBP1), including molecular docking analysis, microscale thermophoresis (MST) assay, co-immunoprecipitation analysis and activity verification, has been further implemented to reveal the key bio-active components in DZXY. Finally, we evaluated the therapeutic efficacy of isochlorogenic acid C (ICAC) based on the results of tumor size, tumor weight, the phospholipid peroxidation pathway, and macrophage phagocytosis in vivo. RESULTS: The present study demonstrated that phospholipid peroxides, as determined by LC-MS/MS-based phospholipidomics, triggered in macrophages, which in turn compromised their capacity to eliminate tumor cells through phagocytosis. Furthermore, we elucidate the mechanism behind stress-induced PEBP1 to form a complex with ALOX15, thereby mediating membrane phospholipid peroxidation in macrophages. DZXY, demonstrates potent anti-breast cancer therapeutic effects by disrupting the ALOX15/PEBP1 interaction and inhibiting phospholipid peroxidation, ultimately enhancing macrophages' phagocytic capability towards tumor cells. Notably, ICAC emerged as a promising active component in DZXY, which can inhibit the ALOX15/PEBP1 interaction, thereby mitigating phospholipid peroxidation in macrophages. CONCLUSION: Collectively, our findings elucidate stress increases the susceptibility of breast cancer by driving lipid peroxidation of macrophages and suggest the ALOX15/PEBP1 complex as a promising intervention target for DZXY.

Anisotropic Diffusion of Elongated Particles in Active Coherent Flows.

The study of particle diffusion, a classical conundrum in scientific inquiry, holds manifold implications for various real-world applications. Particularly within the domain of active flows, where the motion of self-propelled particles instigates fluid movement, extensive research has been dedicated to unraveling the dynamics of passive spherical particles. This scrutiny has unearthed intriguing phenomena, such as superdiffusion at brief temporal scales and conventional diffusion at longer intervals. In contrast to the spherical counterparts, anisotropic particles, which manifest directional variations, are prevalent in nature. Although anisotropic behavior in passive fluids has been subject to exploration, enigmatic aspects persist in comprehending the interplay of anisotropic particles within active flows. This research delves into the intricacies of anisotropic passive particle diffusion, exposing a notable escalation in translational and rotational diffusion coefficients, as well as the superdiffusion index, contingent upon bacterial concentration. Through a detailed examination of particle coordinates, the directional preference of particle diffusion is not solely dependent on the particle length, but rather determined by the ratio of the particle length to the associated length scale of the background flow field. These revelations accentuate the paramount importance of unraveling the nuances of anisotropic particle diffusion within the context of active flows. Such insights not only contribute to the fundamental understanding of particle dynamics, but also have potential implications for a spectrum of applications.

Carbomer Hydrogel Composed of Cu2O and Hematoporphyrin Monomethyl Ether Promotes the Healing of Infected Wounds.

Infectious wounds pose a significant challenge in the field of wound healing primarily due to persistent inflammation and the emergence of antibiotic-resistant bacteria. To combat these issues, the development of an effective wound dressing that can prevent infection and promote healing is of the utmost importance. Photodynamic therapy (PDT) has emerged as a promising noninvasive treatment strategy for tackling antibiotic-resistant bacteria. A biodegradable photosensitizer called hematoporphyrin monomethyl ether (HMME) has shown potential in generating reactive oxygen species (ROS) upon laser activation to combat bacteria. However, the insolubility of HMME limits its antibacterial efficacy and its ability to facilitate skin healing. To overcome these limitations, we have synthesized a compound hydrogel by combining carbomer, HMME, and Cu2O nanoparticles. This compound hydrogel exhibits enhanced antimicrobial ability and excellent biocompatibility and promotes angiogenesis, which is crucial for the healing of skin defects. By integrating the benefits of HMME, Cu2O nanoparticles, and the gel-forming properties of carbomer, this compound hydrogel shows great potential as an effective wound dressing material. In summary, the compound hydrogel developed in this study offers a promising solution for infectious wounds by addressing the challenges of infection prevention and promoting skin healing. This innovative approach utilizing PDT and the unique properties of the compound hydrogel could significantly improve the outcomes of wound healing in clinical settings.