Carbon Dots Crosslinked Egg White Hydrogel for Tissue Engineering.

Egg white (EW)-derived hydrogels hold promise as biomaterials for in vitro cell culture due to their ability to mimic the extracellular matrix. However, their highly cross-linked structures restrict their potential for in vivo applications, as they are unable to integrate dynamically with tissues before degradation. In this study, this limitation is addressed by introducing carbon dots (CDs) as cross-linking agents for EW in a dilute aqueous solution. The resulting CDs-crosslinked EW hydrogel (CEWH) exhibits tensile strength comparable to that of skin tissue and features a large pore structure that promotes cell infiltration. Subcutaneous implantation of CEWH demonstrated excellent integration with surrounding tissue and a degradation rate aligned with the hair follicles (HFs) regeneration cycle. This allows the long-term regeneration and establishment of an M2 macrophage-dominated immune microenvironment, which in turn promotes the re-entry of HFs into the anagen phase from the telogen phase. Additionally, CEWH demonstrated potential as a wound dressing material. Overall, this study paves the way for utilizing EW as a versatile biomaterial for tissue engineering.

d-arginine-functionalized carbon dots with enhanced near-infrared emission and prolonged metabolism time for tumor fluorescent-guided photothermal therapy.

Carbon dots (CDs) have garnered significant interest owing to their distinctive optical properties. However, their bioimaging and biomedical applications are limited by pronounced fluorescence (FL) quenching in aqueous media and low tumor accumulation efficacy associated with their ultra-small size. This study proposes a simple surface modification approach using functioning d-arginine on CDs (d-Arg@CDs) to improve their near-infrared (NIR) FL in aqueous solution and maintain their high photothermal conversion properties. Because of the low utilization rate of dextral amino acids in animals, modifying CDs with low molecular weight d-arginine did not increase particle size but extended the metabolism time in blood circulation, thereby leading to enhanced accumulation efficacy at tumor sites in the mice model. The enhanced tumor accumulation of d-Arg@CDs resulted in significantly superior tumor NIR FL imaging and photothermal therapy performance compared with pure CDs and l-arginine functionalized CDs. This dextral amino acid modification approach is expected to be an effective tool for enhancing the biomedical applications of CDs.

Association of the panimmune-inflammatory value (PIV) with all-cause and cardiovascular mortality in maintenance hemodialysis patients: a propensity score matching retrospective study.

PURPOSE: The panimmune-inflammatory value (PIV) is a novel inflammatory indicator. However, its role in maintenance hemodialysis (MHD) remains unclear. Our goal was to explore the predictive value of PIV for cardiovascular and all-cause mortality in MHD patients. METHODS: In this retrospective cohort study, 507 patients receiving MHD between November 2017 and December 2022 were enrolled. The PIV value was calculated as follows: neutrophil count × monocyte count × platelet count/lymphocyte count. Patients were divided into two groups on the basis of the median PIV. Propensity score matching (PSM) was used to adjust for imbalances in baseline information between groups. Kaplan‒Meier curves, Cox regression, the Fine‒Gray competing risk model, and restricted cubic spline (RCS) curves were used to analyze the relationship between PIV and mortality. RESULTS: By the end of follow-up, 126 deaths had occurred, 91 of which were due to cardiovascular disease. The Kaplan‒Meier curves demonstrated that MHD patients with higher PIV levels had a poorer prognosis for all-cause death (p = 0.019). PIV levels were linked to all-cause death in multivariate Cox proportional risk regression (HR = 1.76; 95% CI 1.14, 2.72; p = 0.011). The Fine‒Gray model revealed a greater cumulative incidence of cardiovascular death in the higher PIV group (p = 0.035). PIV levels were linked to cardiovascular mortality in the Fine‒Gray competing risk model (HR = 2.06; 95% CI 1.25, 3.42; p = 0.005). The RCS revealed a nonlinear relationship between PIV and mortality risk (p < 0.05). Using 63 years of age as the threshold, we observed a multiplicative interaction effect between age and PIV for all-cause mortality (p = 0.006). CONCLUSION: In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality.

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. CONCLUSION: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

Conditional generative adversarial network-assisted system for radiation-free evaluation of scoliosis using a single smartphone photograph: a model development and validation study.

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Natural pachypodol integrated, lung targeted and inhaled lipid nanomedicine ameliorates acute lung injury via anti-inflammation and repairing lung barrier.

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a high-mortality disease caused by multiple disorders such as COVID-19, influenza, and sepsis. Current therapies mainly rely on the inhalation of nitric oxide or injection of pharmaceutical drugs (e.g., glucocorticoids); however, their toxicity, side effects, or administration routes limit their clinical application. In this study, pachypodol (Pac), a hydrophobic flavonol with anti-inflammatory effects, was extracted from Pogostemon cablin Benth and intercalated in liposomes (Pac@liposome, Pac-lipo) to improve its solubility, biodistribution, and bioavailability, aiming at enhanced ALI/ARDS therapy. Nanosized Pac-lipo was confirmed to have stable physical properties, good biodistribution, and reliable biocompatibility. In vitro tests proved that Pac-lipo has anti-inflammatory property and protective effects on endothelial and epithelial barriers in lipopolysaccharide (LPS)-induced macrophages and endothelial cells, respectively. Further, the roles of Pac-lipo were validated on treating LPS-induced ALI in mice. Pac-lipo showed better effects than did Pac alone on relieving ALI phenotypes: It significantly attenuated lung index, improved pulmonary functions, inhibited cytokine expression such as TNF-α, IL-6, IL-1ß, and iNOS in lung tissues, alleviated lung injury shown by HE staining, reduced protein content and total cell number in bronchoalveolar lavage fluid, and repaired lung epithelial and vascular endothelial barriers. As regards the underlying mechanisms, RNA sequencing results showed that the effects of the drugs were associated with numerous immune- and inflammation-related signaling pathways. Molecular docking and western blotting demonstrated that Pac-lipo inhibited the activation of the TLR4-MyD88-NF-κB/MAPK signaling pathway. Taken together, for the first time, our new drug (Pac-lipo) ameliorates ALI via inhibition of TLR4-MyD88-NF-κB/MAPK pathway-mediated inflammation and disruption of lung barrier. These findings may provide a promising strategy for ALI treatment in the clinic.

Sprouting facilitates the antiglycative effect of black soybean (Glycine max (L.) Merr.) by promoting the accumulation of isoflavones.

The exposure of advanced glycation end products (AGEs) can induce chronic inflammation, oxidative stress, and accelerated aging, contributing the onset and progression of many diseases especially diabetic complications. Therefore, the searching of antiglycative foods is of practical significance, which may serve as a strategy in the attenuation of AGEs-associated diseases. In this study, we evaluated the antiglycative potential of some beans and bean sprouts that were common in our daily life. The results revealed that sprouting enhanced the antiglycative activity of beans, with black soybean sprouts demonstrating the highest efficacy (4.92-fold higher than the unsprouted beans). To assess practical implications, we examined the antiglycative activity of black soybean sprouts in pork soup, a popular food model that incorporates sprouts. Our findings confirmed the inhibitory effect on a dose-dependent manner. Through open column fractionation, we identified isoflavones and soyasaponin Bb as the candidates responsible for these effects. Additionally, compare to the unsprouted black soybeans, we found significant increases in the levels of antioxidative properties (2.51-fold), total phenolics (7.28-fold), isoflavones, and soyasaponin Bb during the sprouting process. Further studies determined that genistein, genistin, and daidzin were the major antiglycative compounds in black soybean sprouts. Collectively, this study emphasizes the benefits of sprouted beans and offers foundation for the development of functional sprouting foods.

Natural Language Processing Versus Diagnosis Code-Based Methods for Postherpetic Neuralgia Identification: Algorithm Development and Validation.

Background: Diagnosis codes and prescription data are used in algorithms to identify postherpetic neuralgia (PHN), a debilitating complication of herpes zoster (HZ). Because of the questionable accuracy of codes and prescription data, manual chart review is sometimes used to identify PHN in electronic health records (EHRs), which can be costly and time-consuming. Objective: This study aims to develop and validate a natural language processing (NLP) algorithm for automatically identifying PHN from unstructured EHR data and to compare its performance with that of code-based methods. Methods: This retrospective study used EHR data from Kaiser Permanente Southern California, a large integrated health care system that serves over 4.8 million members. The source population included members aged ≥50 years who received an incident HZ diagnosis and accompanying antiviral prescription between 2018 and 2020 and had ≥1 encounter within 90-180 days of the incident HZ diagnosis. The study team manually reviewed the EHR and identified PHN cases. For NLP development and validation, 500 and 800 random samples from the source population were selected, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), F-score, and Matthews correlation coefficient (MCC) of NLP and the code-based methods were evaluated using chart-reviewed results as the reference standard. Results: The NLP algorithm identified PHN cases with a 90.9% sensitivity, 98.5% specificity, 82% PPV, and 99.3% NPV. The composite scores of the NLP algorithm were 0.89 (F-score) and 0.85 (MCC). The prevalences of PHN in the validation data were 6.9% (reference standard), 7.6% (NLP), and 5.4%-13.1% (code-based). The code-based methods achieved a 52.7%-61.8% sensitivity, 89.8%-98.4% specificity, 27.6%-72.1% PPV, and 96.3%-97.1% NPV. The F-scores and MCCs ranged between 0.45 and 0.59 and between 0.32 and 0.61, respectively. Conclusions: The automated NLP-based approach identified PHN cases from the EHR with good accuracy. This method could be useful in population-based PHN research.

Bulk and single-cell RNA-seq analyses reveals canonical RNA editing associated with microglial homeostasis and its role in sepsis-associated encephalopathy.

Previous studies have demonstrated the roles of both microglia homeostasis and RNA editing in sepsis-associated encephalopathy (SAE), yet their relationship remains to be elucidated. In the current study, we analyzed bulk and single-cell RNA-seq (scRNA) datasets containing 107 brain tissues and microglia samples of mice with microglial depletion and repopulation to explore canonical RNA editing associated with microglia homeostasis and evaluated its role in SAE. Analysis of brain RNA-Seq of mice revealed hallmarks of microglial repopulation, including peak expressions of Apobec1 and Apobec3 at Day 5 and dramatically changed B2m RNA editing. Significant time-dependent changes in brain RNA editing during microglial depletion and microglial repopulation was primarily observed in synaptic genes, such as Tbc1d24 and Slc1a2. ScRNA-Seq revealed heterogeneous RNA editing among microglia subpopulations and their distinct changes associated with microglia homeostasis. Moreover, repopulated microglia from LPS-induced septic mice exhibited intensified up-regulation of Apobec1 and Apobec3, with distinct RNA editing responses to LPS, mainly involved in immune-related pathways. The hippocampus from septic mice induced by peritoneal contamination and infection showed upregulated Apobec1 and Apobec3 expression, and altered RNA editing in immune-related genes, such as B2m and Mier1, and nervous-related lncRNA Meg3 and Snhg11, both of which were repressed by microglial depletion. Moreover, expression of complement-related genes, such as C4b and Cd47, were substantially correlated with RNA editing activity in microglia homeostasis and SAE. Our study demonstrates canonical RNA editing associated with microglia homeostasis, and provides new insight into its potential role in SAE.

HOXA1 promotes epithelial-mesenchymal transition and malignant characteristics of laryngeal squamous cell carcinoma.

Despite considerable advancements in the diagnosis and treatment of LSCC, there has been no significant improvement in survival rate. Consequently, identifying molecular targets for this cancer is of paramount importance. HOXA1, a constituent of the homeobox transcription factor cluster, plays a role in the development of various types of cancer. Nevertheless, the specific function and mechanism of HOXA1 in LSCC remains unclear. This study aimed to clarify the impact of HOXA1 on the advancement of LSCC and uncover its underlying mechanism. Our findings indicate that HOXA1 exhibits a significantly elevated expression level in LSCC. Suppression of HOXA1 inhibited the proliferation of LSCC cells. Furthermore, the ablation of HOXA1 triggered the apoptosis of LSCC cells and inhibited EMT. Functionally, HOXA1 has a role in initiating the activation of the PI3K/AKT/mTOR pathway in LSCC cells. In summary, HOXA1 significantly contributes to the EMT of LSCC cells via the PI3K/AKT/mTOR signaling pathway, thereby facilitating the proliferation and motility of LSCC cells. Consequently, HOXA1 presents itself as a viable therapeutic target for LSCC interventions.

Hydroxychloroquine and a low antiresorptive activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.

Osteoporosis remains incurable. The most widely used antiresorptive agents, bisphosphonates (BPs), also inhibit bone formation, while the anabolic agent, teriparatide, does not inhibit bone resorption, and thus they have limited efficacy in preventing osteoporotic fractures and cause some side effects. Thus, there is an unmet need to develop dual antiresorptive and anabolic agents to prevent and treat osteoporosis. Hydroxychloroquine (HCQ), which is used to treat rheumatoid arthritis, prevents the lysosomal degradation of TNF receptor-associated factor 3 (TRAF3), an NF-κB adaptor protein that limits bone resorption and maintains bone formation. We attempted to covalently link HCQ to a hydroxyalklyl BP (HABP) with anticipated low antiresorptive activity, to target delivery of HCQ to bone to test if this targeting increases its efficacy to prevent TRAF3 degradation in the bone microenvironment and thus reduce bone resorption and increase bone formation, while reducing its systemic side effects. Unexpectedly, HABP-HCQ was found to exist as a salt in aqueous solution, composed of a protonated HCQ cation and a deprotonated HABP anion. Nevertheless, it inhibited osteoclastogenesis, stimulated osteoblast differentiation, and increased TRAF3 protein levels in vitro. HABP-HCQ significantly inhibited both osteoclast formation and bone marrow fibrosis in mice given multiple daily PTH injections. In contrast, HCQ inhibited marrow fibrosis, but not osteoclast formation, while the HABP alone inhibited osteoclast formation, but not fibrosis, in the mice. HABP-HCQ, but not HCQ, prevented trabecular bone loss following ovariectomy in mice and, importantly, increased bone volume in ovariectomized mice with established bone loss because HABP-HCQ increased bone formation and decreased bone resorption parameters simultaneously. In contrast, HCQ increased bone formation, but did not decrease bone resorption parameters, while HABP also restored the bone lost in ovariectomized mice, but it inhibited parameters of both bone resorption and formation. Our findings suggest that the combination of HABP and HCQ could have dual antiresorptive and anabolic effects to prevent and treat osteoporosis.

Effects of Surface Crack Shape on Fracture Behavior of Oil Pipelines Based on the MMC Criterion.

This study employs a hybrid numerical-experimental calibration method based on phenomena to determine the fracture parameters of the Modified Mohr-Coulomb (MMC) model. Using a self-developed VUMAT subroutine and the element deletion technique, the fracture process of a wide plate pipeline is thoroughly analyzed. This study investigates the impact of various crack shapes on the fracture response under tensile loading and the influence of surface crack size on the initiation location of a wide plate. These results demonstrate the calibrated MMC fracture model's accurate prediction of the toughness fracture behavior of X80 pipeline steel. Under equal area conditions of the dangerous section, circular cracks exhibit lower bearing capacity compared to elliptical cracks. Elliptical cracks predominantly propagate in the thickness direction, whereas circular cracks show nearly uniform growth in all directions. Furthermore, when the crack depth is less than half of the wall thickness, the damage accumulation value at the midpoint of the crack front is maximized; conversely, when the crack front is closer to the internal measurement point of the wide plate, the damage accumulation value is maximized.

CUL1 exacerbates glucocorticoid-induced osteoporosis by enhancing ASAP1 ubiquitination.

BACKGROUND: Glucocorticoid-induced osteoporosis is a leading secondary cause of osteoporosis. Cullin-1 (CUL1) levels are abnormally elevated in patients with osteoporosis, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the mechanism of action of CUL1 in a glucocorticoid (dexamethasone, Dex)-induced osteoporosis model. METHODS: C57BL/6J mice were intraperitoneally injected with Dex to establish an osteoporosis model. Mouse femur bone injury and bone formation were detected using hematoxylin-eosin or Masson staining. Apoptosis and cell cycle distribution were determined by flow cytometry. Alkaline phosphatase (ALP) activity and calcified nodules were monitored using ALP and Alizarin Red S staining. The molecular mechanism was validated by co-immunoprecipitation (Co-IP) and ubiquitination assays. RESULTS: CUL1 expression was enhanced in the Dex-induced osteoporosis mouse model. CUL1 silencing moderated the Dex-induced cell proliferation and osteogenesis inhibition. Moreover, CUL1 promoted the ubiquitination and degradation of ASAP1 via the SKP1-CUL1-F-box (SCF)-FBXW7 complex. CUL1 induced apoptosis and repressed osteogenesis by ASAP1. CUL1 silencing alleviated the Dex-induced osteoporosis in mice. CONCLUSION: CUL1 suppressed osteoblast proliferation and osteogenesis by promoting ASAP1 ubiquitination via the SCF-FBXW7 complex in glucocorticoid-induced osteoporosis.

Base-Promoted Ring Expansion Reaction of 4-Quinolones To Access Benzazepinones.

4-Quinolone derivatives undergo an unexpected ring expansion reaction with α-halo esters/phosphonates/sulfones in the presence of a base, such as NaH, to produce novel benzazepinones. Under these mild and transition-metal-free conditions, most substrates gave moderate to excellent yields. The reaction could be applied in gram-scale synthesis of drug-like molecules that greatly accelerated our structure-activity relationship studies. A plausible mechanism was proposed.

Exploring the sensory acceptance, physicochemical properties, and phenolamide leaching characteristics of rose tea.

The consumption of rose tea has gained popularity due to its unique flavor and health benefits. In particular, previous data exemplified the protective role of N1, N5, N10-(E)-tri-p-coumaroylspermidine (ETCS; a phenolamide) against alcohol-induced hepatic injuries. This study evaluated the customer acceptance and physicochemical properties of eight rose tea varieties that available in the market. In general, Qianye rose (Rosa centifolia) exhibits better flavor and taste, while Hetian rose (Rosa damascena Mill.) has the highest ETCS level. Moreover, a negative correlation between ETCS content and both vitamin C and anthocyanins content in rose is observed. Additionally, the optimal brewing conditions for rose tea is 95 °C mineral water for 5 min in a thermos bottle, based on ETCS level in the infusion. And rose tea can be brewed for at least three times. Collectively, our findings provide valuable insights for rose tea drinkers and individuals interested in the dietary hepatic-protective benefits.

Olink Proteomics for the Identification of Biomarkers for Early Diagnosis of Postmenopausal Osteoporosis.

This investigation aims to employ Olink proteomics in analyzing the distinct serum proteins associated with postmenopausal osteoporosis (PMOP) and identifying prognostic markers for early detection of PMOP via molecular mechanism research on postmenopausal osteoporosis. Postmenopausal women admitted to Beijing Jishuitan Hospital were randomly selected and categorized into three groups based on their dual-energy X-ray absorptiometry (DXA) T-scores: osteoporosis group (n = 24), osteopenia group (n = 20), and normal bone mass group (n = 16). Serum samples from all participants were collected for clinical and bone metabolism marker measurements. Olink proteomics was utilized to identify differentially expressed proteins (DEPs) that are highly associated with postmenopausal osteoporosis. The functional analysis of DEPs was performed using Gene Ontology and Kyto Encyclopedia Genes and Genomes (KEGG). The biological characteristics of these proteins and their correlation with PMOP were subsequently analyzed. ROC curve analysis was performed to identify potential biomarkers with the highest diagnostic accuracy for early stage PMOP. Through Olink proteomics, we identified five DEPs highly associated with PMOP, including two upregulated and three downregulated proteins. TWEAK and CDCP1 markers exhibited the highest area under the curve (0.8188 and 0.8031, respectively). TWEAK and CDCP1 have the potential to serve as biomarkers for early prediction of postmenopausal osteoporosis.

Comparative study of PGCs cultivation systems HiS and FAcs: a transcriptomic and cellular biology perspective.

In chicken, primordial germ cells (PGC) are crucial for the preservation and manipulation of genetic resources in poultry production. The HiS and FAcs culture systems are two important methods for the in vitro cultivation of chicken PGCs. The purpose of this study was to compare and analyze the two cultivation systems for PGCs (His and FAcs culture systems) to assess their efficacy and applicability in supporting PGC growth, maintaining PGC characteristics, and lineage transmission ability. The study found that both HiS and FAcs culture systems could maintain the basic biological characteristics of chicken PGCs, including the simultaneous expression of pluripotency and reproductive marker genes, as well as the presence of abundant glycogen granules. Subsequently, we identified 2,145 differentially expressed genes (DEG) through RNA sequencing. GO and KEGG analysis revealed a large number of DEGs enriched in the cell adhesion and calcium ion binding pathways, and the analysis found that these genes maintained a higher level in HiS-PGCs. Further personalized analysis found that the regulatory genes for maintaining PGC pluripotency were highly expressed in HiS-PGCs, while germ cell-related genes showed similar expression in both systems. Additionally, through RNA sequencing data and cell proliferation ability, it was found that PGCs in the FAcs system had a higher proliferation rate and a faster cell cycle. Finally, it was discovered that the expression of cell migration-related genes was maintained at a higher level in HiS-PGCs, but the migration efficiency of HiS-PGCs did not show a significant difference compared to FAcs-PGCs. These results suggest that both HiS and FAcs culture systems can maintain the proliferation and basic characteristics of chicken PGCs, but differences exist in cell proliferation, pluripotency regulation, and cell adhesion. These findings provide new information for optimizing PGC cultivation systems and are important for the preservation and genetic improvement of chicken PGCs.

Remediation of cadmium contaminated soil using electrokinetic-phytoremediation system with rotary switching electrodes.

Considering both electrokinetic remediation and phytoremediation have limitations, an electrokinetic phytoremediation (EP) system was constructed to obtain efficient and environmentally friendly remediation results. This study indicates that the electric field can promote the absorption of Cd by ryegrass with little impact on soil physicochemical properties under the condition of rotary switching electrodes, and the accumulation of Cd in the aboveground and underground parts of ryegrass increased by 145.2% and 93.7%, respectively. The DC electric field combined with ryegrass under rotary switching electrode mode proved to be the optimal condition for the remediation of Cd contaminated soil with a remediation efficiency of 66.7%. Moreover, the rotary switching of the electrodes alleviated the suppression of the growth of ryegrass by the DC electric field. During the EP remediation process, the electric field promoted the transformation of the residue state of Cd to the other forms, which accelerated the desorption rate of Cd from the soil and facilitated the migration of Cd into plants. In conclusion, EP is a green and efficient remediation technology for heavy metal contaminated soil with good application prospects.

Combination Therapy Consisting of Transarterial Chemoembolization, Lenvatinib, and Programmed Cell Death Protein 1 Blockade for Hepatocellular Carcinoma with Inferior Vena Cava Tumor Thrombus: A Case Series Study and Literature Review.

INTRODUCTION: Patients with hepatocellular carcinoma (HCC) and inferior vena cava tumor thrombus (IVCTT) have poor prognosis. Combination therapy involving the blockade of programmed cell death protein 1 (PD-1) and tyrosine kinase inhibitors is an efficient treatment strategy for advanced HCC. However, surgical treatment after a combination of systemic therapy and transarterial chemoembolization (TACE) for HCC with IVCTT has not been widely reported, and the efficacy and safety of this treatment have not been studied. METHODS: In the 21 cases reported herein, the patients were treated with TACE, lenvatinib, and PD-1 blockade. The treatment responses, progression-free survival (PFS), overall survival (OS), disease control rate, and toxicities were evaluated, and the related literature was reviewed. RESULTS: The overall response and disease control rates were 66.7% and 85.7%, respectively. The median PFS time was 16.0 months, with a 1-year PFS rate of 55.60%. The median OS was not reached, with a 1-year OS rate of 66.70%. Four patients underwent hepatectomy without serious complications and survived for 29.1, 24.7, 14.2, and 13.8 months. Three patients survived tumor-free, and 1 patient experienced intrahepatic recurrence. Pathological complete response and major pathological responses were observed in 1 and 3 patients, respectively. Treatment-related adverse events of any grade occurred in 8/9 patients (88.9%), and grade 3 treatment-related adverse events occurred in 1 patient. CONCLUSION: The combination of TACE, lenvatinib, and PD-1 is effective for HCC with IVCTT and has acceptable adverse effects.

ZBTB46 coordinates angiogenesis and immunity to control tumor outcome.

Tumor angiogenesis and immunity show an inverse correlation in cancer progression and outcome1. Here, we report that ZBTB46, a repressive transcription factor and a widely accepted marker for classical dendritic cells (DCs)2,3, controls both tumor angiogenesis and immunity. Zbtb46 was downregulated in both DCs and endothelial cells by tumor-derived factors to facilitate robust tumor growth. Zbtb46 downregulation led to a hallmark pro-tumor microenvironment (TME), including dysfunctional vasculature and immunosuppressive conditions. Analysis of human cancer data revealed a similar association of low ZBTB46 expression with an immunosuppressive TME and a worse prognosis. In contrast, enforced Zbtb46 expression led to TME changes to restrict tumor growth. Mechanistically, Zbtb46-deficient endothelial cells were highly angiogenic, and Zbtb46-deficient bone marrow progenitors upregulated Cebpb and diverted the DC program to immunosuppressive myeloid lineage output, potentially explaining the myeloid lineage skewing phenomenon in cancer4. Conversely, enforced Zbtb46 expression normalized tumor vessels and, by suppressing Cebpb, skewed bone marrow precursors toward immunostimulatory myeloid lineage output, leading to an immune-hot TME. Remarkably, Zbtb46 mRNA treatment synergized with anti-PD1 immunotherapy to improve tumor management in preclinical models. These findings identify ZBTB46 as a critical factor for angiogenesis and for myeloid lineage skewing in cancer and suggest that maintaining its expression could have therapeutic benefits.