miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

A Guideline Strategy for Identifying Genes/Proteins Regulating Antiviral Innate Immunity.

Antiviral innate immunity is a complicated system initiated by the induction of type I interferon (IFN-I) and downstream interferon-stimulated genes (ISGs) and is finely regulated by numerous positive and negative factors at different signaling adaptors. During this process, posttranslational modifications, especially ubiquitination, are the most common regulatory strategy used by the host to switch the antiviral innate signaling pathway and are mainly controlled by E3 ubiquitin ligases from different protein families. A comprehensive understanding of the regulatory mechanisms and a novel discovery of regulatory factors involved in the IFN-I signaling pathway are important for researchers to identify novel therapeutic targets against viral infectious diseases based on innate immunotherapy. In this section, we use the E3 ubiquitin ligase as an example to guide the identification of a protein belonging to the RING Finger (RNF) family that regulates the RIG-I-mediated IFN-I pathway through ubiquitination.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease.

JOURNAL/nrgr/04.03/01300535-202508000-00026/figure1/v/2024-09-30T120553Z/r/image-tiff Interferon regulatory factor 7 plays a crucial role in the innate immune response. However, whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown. Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells. Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype. In addition, siRNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase, tumor necrosis factor α, CD16, CD32, and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1. Taken together, our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Binary ruthenium dioxide and nickel oxide ultrafine particles loaded on carbon nanotubes for high-stability oxygen evolution reaction at high current densities.

RuO2 is an efficient electrocatalyst for the oxygen evolution reaction (OER). However, during the OER process, RuO2 is prone to oxidation into Rux+ (x > 4), leading to its dissolution in the electrolyte and resulting in poor stability of RuO2. Here, we report a bicomponent electrocatalyst, NiO and RuO2 co-loaded on carbon nanotubes (RuO2/NiO/CNT). The results demonstrate that the introduction of NiO suppresses the over-oxidation of RuO2 during the OER process, not only inheriting the excellent catalytic performance of RuO2, but also significantly enhancing the stability of the catalyst for OER at high current densities. In contrast to RuO2/CNT, RuO2/NiO/CNT shows no significant change in activity after 150 h of OER at a current density of 100 mA cm-2. Density functional theory (DFT) calculations indicate that NiO transfers a large number of electrons to RuO2, thereby reducing the oxidation state of Ru. In conclusion, this study provides a detailed analysis of the phenomenon where low-valent metal oxides have the ability to enhance the stability of RuO2 catalysts.

Sodium chloride-assisted CVD enables controlled synthesis of large single-layered MoS2.

Thin-layer MoS2 has attracted much interest because of its potential in diverse technologies, including electronics, optoelectronics and catalysis these few years. In particular, finding a simple and effective solution for large-scale growth of thin-layer semiconductor nanosheets is a prerequisite for achieving their excellent performance. In this paper, we investigated four different substrates under identical conditions for MoS2 film growth and observed a strong correlation between substrate surface conditions and MoS2 growth. To enhance substrate performance, a low-concentration NaCl water solution (25 mg mL-1) was employed for pre-treating the substrate surface, thereby modifying its initial state. In the chemical vapor deposition (CVD) growth environment, the introduced halide ions served as surface dangling bonds. The pre-treated led to a remarkable 90% increase in the growth rate of MoS2 on the substrate surface, facilitating the production of large monolayer MoS2 sheets (∼200 µm). This growth mechanism further enabled the manufacturing of ultra-large single crystals (∼1 mm). Consequently, our research presents a straightforward and cost-effective approach for the large-scale production of nanosheets. Field-effect transistors (FETs) based on the pre-treated monolayer MoS2 exhibited high mobility (12 cm2 V-1 s-1) and a large on/off ratio (104). Therefore, our research provides a simple and low-cost approach for large-scale production of nanosheets for use in high-quality electronics over large areas.

Comparative Analysis of Lennox-Gastaut Syndrome With Different Subtypes of Tonic Seizures: A Single-Center Retrospective Cohort Study.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is one of the most severe childhood-onset epileptic encephalopathies, primarily characterized by tonic seizures. In clinical practice, we have identified various subtypes of tonic seizures in LGS. This study aimed to analyze the clinical characteristics, electrographic features, treatment responses, and prognosis across different subtypes of LGS. METHODS: This retrospective cohort study included 46 patients diagnosed with LGS at our center between January 2017 and January 2020. Patients were classified into four groups based on tonic seizure subtypes: Group A (tonic), Group B (spasm-tonic), Group C (myoclonic-tonic), and Group D (combination of spasm-tonic and myoclonic-tonic). Comprehensive clinical data were collected and analyzed. RESULTS: Of the 46 patients, 33 were male. The mean age of onset for Group B (12.38 ± 7.85 months) was significantly less than those of the other three groups (P = 0.02). No significant differences in etiology were found among the groups. Genetic analysis identified mutations in SCN8A, MCCC2, STXBP1, GABRB3, and CACNA1H. After a minimum follow-up of 24 months, the treatment outcomes were more favorable in Groups A and C, whereas psychomotor development was notably poorer in Groups B and D. CONCLUSIONS: The findings of this study suggest that LGS may present with distinct subtypes of tonic seizures, with spasm-tonic seizures presenting at an earlier age. Patients with LGS experiencing spasm-tonic seizures, with or without myoclonic-tonic seizures, exhibited poorer treatment responses and psychomotor development than those with other subtypes.

Platelet factors ameliorate thoracic aortic aneurysm and dissection by inhibiting the FGF-FGFR cascade activation in aortic-endothelial cell.

Thoracic aortic aneurysm and dissection (TAAD) is closely associated with vascular endothelial dysfunction. Platelet factor 4 (PF4) is crucial for maintaining vascular endothelial cell homeostasis. However, whether PF4 can influence the progression of TAAD remains unknown. In the present study, we constructed a liposome-encapsulated PF4 nanomedicine and verified its effect on BAPN-induced TAAD in vivo. We found that liposome PF4 nanoparticles (Lipo-PF4), more effectively than PF4 alone, inhibited the formation of TAAD. In vitro, PF4 improved endothelial cell function under pathological conditions by inhibiting migratory and angiogenic abilities of human aortic endothelial cells (HAECs). Mechanically, PF4 inhibited the development of TAAD and improved HAECs function by combining with heparin sulfate and blocking fibroblast growth factor-fibroblast growth factor receptor (FGF-FGFR) signaling. Taken together, we developed a nano-drug (Lipo-PF4) that effectively ameliorates the progression of TAAD by improving endothelial function. Lipo-PF4 is expected to be a therapeutic option for TAAD in the future.

LlbHLH87 interacts with LlSPT to modulate thermotolerance via activation of LlHSFA2 and LlEIN3 in lily.

Basic helix-loop-helix (bHLH) proteins comprise one of the largest families of transcription factors in plants, which play roles in plant development, secondary metabolism, and the response to biotic/abiotic stresses. However, the roles of bHLH proteins in thermotolerance are largely unknown. Herein, we identified a heat-inducible member of the bHLH family in lily (Lilium longiflorum), named LlbHLH87, which plays a role in thermotolerance. LlbHLH87 was rapidly induced by transient heat stress, and its encoded protein was localized to the nucleus, exhibiting transactivation activity in both yeast and plant cells. Overexpression of LlbHLH87 in Arabidopsis enhanced basal thermotolerance, while silencing of LlbHLH87 in lily reduced basal thermotolerance. Further analysis showed that LlbHLH87 bound to the promoters of HEAT STRESS TRANSCRIPTION FACTOR A2 (LlHSFA2) and ETHYLENE-INSENSITIVE 3 (LlEIN3) to directly activate their expression. In addition, LlbHLH87 interacted with itself and with SPATULA (LlSPT) protein. LlSPT was activated by extended heat stress and its protein competed for the homologous interaction of LlbHLH87, which reduced the transactivation ability of LlbHLH87 for target genes. Compared with that observed under LlbHLH87 overexpression alone, co-overexpression of LlbHLH87 and LlSPT reduced the basal thermotolerance of lily to sudden heat shock, but improved its thermosensitivity to prolonged heat stress treatment. Overall, our data demonstrated that LlbHLH87 regulates thermotolerance via activation of LlEIN3 and LlHSFA2, along with an antagonistic interaction with LlSPT.

Comparison of long-term quality of life and their predictors in survivors between paediatric and adult nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

BACKGROUND: To compare the differences in long-term quality of life (QoL) between survivors of paediatric and adult patients with nasopharyngeal carcinoma (NPC) and assess the clinical factors that predict long-term QoL. METHODS: We enrolled 420 long-term NPC survivors who were alive for at least 8 years after treatment, including 195 paediatric and 225 adult patients diagnosed and treated with intensity-modulated radiotherapy (IMRT) at Sun Yat-sen University Cancer Centre (SYSUCC) between 2011 and 2015. Data on clinical factors and EORTC QLQ-C30 were collected from all participants. The QoL of paediatric and adult NPC survivors was compared. RESULTS: The paediatric group had significantly better outcomes in global health status (paediatric: 80.2 ± 12.7; adult: 77.2 ± 11.5; P = 0.027), physical function (paediatric: 98.5 ± 4.6; adult: 95.1 ± 7.0; P < 0.001), role function (paediatric: 97.0 ± 9.2; adult: 90.5 ± 15.2; P < 0.001), social function (paediatric: 96.0 ± 8.9; adult: 93.5 ± 11.8; P = 0.038), insomnia (paediatric: 1.9 ± 7.8; adult: 13.1 ± 22.3; P < 0.001), constipation (paediatric: 1.3 ± 7.5; adult: 8.0 ± 17.4; P < 0.001), diarrhea (paediatric: 0.7 ± 4.6; adult: 2.8 ± 9.3; P = 0.010), and financial difficulties (paediatric: 1.9 ± 7.8; adult: 11.0 ± 19.8; P < 0.001), but poorer cognitive function (paediatric: 88.3 ± 9.9; adult: 93.8 ± 12.6; P < 0.001) than the adult group. Pretreatment clinical factors, including T stage, N stage, and pre-treatment EBV (Epstein-Barr Virus) DNA, showed a strong association with QoL. However, the factors that affected the QoL outcomes differed between the two groups. In survivors of paediatric cancer, global health status/QoL was strongly correlated with T stage (P < 0.001) and clinical stage (P = 0.018), whereas it was strongly correlated with pre-treatment EBV DNA (P = 0.008) in adults. CONCLUSION: Paediatric survivors of NPC have a significantly better QoL than adult NPC survivors. Moreover, pre-treatment T stage, N stage, and EBV DNA significantly influenced the overall health status of the survivors. These results highlight the need to tailor care to both age groups to promote better long-term health outcomes.

Hyaluronic acid methacrylate/Pluronic F127 hydrogel enhanced with spermidine-modified mesoporous polydopamine nanoparticles for efficient synergistic periodontitis treatment.

Bacterial infection, reactive oxygen species (ROS) accumulation, and persistent inflammation pose significant challenges in the treatment of periodontitis. However, the current single-modal strategy makes achieving the best treatment effect difficult. Herein, we developed a double-network hydrogel composed of Pluronic F127 (PF-127) and hyaluronic acid methacrylate (HAMA) loaded with spermidine-modified mesoporous polydopamine nanoparticles (M@S NPs). The PF-127/HAMA/M@S (PH/M@S) hydrogel was injectable and exhibited thermosensitivity and photocrosslinking capabilities, which enable it to adapt to the irregular shape of periodontal pockets. In vitro, the PH/M@S displayed multiple therapeutic effects, such as photothermal antibacterial activity, a high ROS scavenging capacity, and anti-inflammatory effects, which are beneficial for the multimodal treatment of periodontitis. The underlying anti-inflammatory mechanism of this hydrogel involves suppression of the extracellular regulated protein kinase 1/2 and nuclear factor kappa-B signalling pathways. Furthermore, in lipopolysaccharide-stimulated macrophage conditioned media, the PH/M@S effectively restored the osteogenic differentiation potential. In a rat model of periodontitis, the PH/M@S effectively reduced the bacterial load, relieved local inflammation and inhibited alveolar bone resorption. Collectively, these findings highlight the versatile functions of the PH/M@S, including photothermal antibacterial activity, ROS scavenging, and anti-inflammatory effects, indicating that this hydrogel is a promising multifunctional filling material for the treatment of periodontitis.

The relationship between the secondary structure and the emulsifying ability of protein-based particles and the Pickering emulsions stabilized by the zein-lysine complex.

Due to the sustainability and widespread use of proteins, protein-based materials are extensively utilized in the preparation of Pickering emulsions. However, the relationship between the secondary structure of proteins and their emulsifying ability has not been further investigated. This study used the addition of three different amino acids to influence the interaction between zein chains, which may induce changes in the secondary structure of the prepared zein complex particles. This study demonstrates that the emulsifying properties of proteins, such as dispersibility, zeta potential, three-phase contact angles, interfacial affinity, adsorption rates, and the volume of the stabilized oil phase, are closely related to the ß-sheet content of the complex particles, providing a theoretical reference for protein-based stabilizers. Additionally, amino acids, as the blocks of proteins, have high compatibility with proteins, and using amino acids as modifiers aligns with the safety requirements for food processing. In this study, the prepared zein-lysine complex particles have good emulsifying ability, capable of stabilizing a 50 (v/v)% emulsion at a lower concentration (10 mg mL-1), and the prepared emulsion exhibits high-temperature stability and ionic resistance. This characteristic makes the emulsion potentially valuable for application in systems with high salt concentrations and those that may undergo heat treatment.

A novel endoscopic artificial intelligence system to assist in the diagnosis of autoimmune gastritis: a multicenter study.

BACKGROUND & AIMS: Autoimmune gastritis (AIG), distinct from Helicobacter pylori-associated atrophic gastritis (HpAG), is underdiagnosed due to limited awareness. This multicenter study aims to develop a novel endoscopic artificial intelligence (AI) system assisting in AIG diagnosis. METHODS: Patients diagnosed with AIG, as well as HpAG and non-atrophic gastritis (NAG), were retrospectively enrolled from six centers. Endoscopic images with relevant demographic and medical data, were collected for the development of AI-assisted system, SEER-SCOPE AI, based on multi-site feature fusion model. The diagnostic performance of SEER-SCOPE AI was evaluated in the internal and external datasets. Endoscopists' performance with and without AI support was tested and compared using Mann-Whitney U test. Heatmap analysis was performed to interpret SEER-SCOPE AI. RESULTS: 1 070 patients (294 AIG, 386 HpAG, 390 NAG) with 18 828 endoscopy images were collected. SEER-SCOPE AI achieved strong performance for identifying AIG, with 96.9% sensitivity, 92.2% specificity and an AUROC of 0.990 internally, and 90.3% sensitivity, 93.1% specificity and an AUROC of 0.973 externally. The performance of SEER-SCOPE AI (sensitivity 91.3%) was comparable to experts (87.3%) and significantly outperformed non-experts (70.0%). With AI support, the overall performance of endoscopists was improved (sensitivity: 90.3% [95% CI 86.0%-93.2%] vs. 78.7% [95% CI 73.6%-83.2%], p=0.008). Heatmap analysis revealed consistent focus of SEER-SCOPE AI on regions corresponding to atrophic areas. CONCLUSIONS: SEER-SCOPE AI demonstrated expert-level performance in identifying AIG, and enhanced the diagnostic ability of endoscopists. Its application holds promise as a potent endoscopy-assisted tool for guiding biopsy sampling and early detection of AIG.

An Overview of the Mechanisms through Which Plants Regulate ROS Homeostasis under Cadmium Stress.

Cadmium (Cd2+) is a non-essential and highly toxic element to all organic life forms, including plants and humans. In response to Cd stress, plants have evolved multiple protective mechanisms, such as Cd2+ chelation, vesicle sequestration, the regulation of Cd2+ uptake, and enhanced antioxidant defenses. When Cd2+ accumulates in plants to a certain level, it triggers a burst of reactive oxygen species (ROS), leading to chlorosis, growth retardation, and potentially death. To counteract this, plants utilize a complex network of enzymatic and non-enzymatic antioxidant systems to manage ROS and protect cells from oxidative damage. This review systematically summarizes how various elements, including nitrogen, phosphorus, calcium, iron, and zinc, as well as phytohormones such as abscisic acid, auxin, brassinosteroids, and ethylene, and signaling molecules like nitric oxide, hydrogen peroxide, and hydrogen sulfide, regulate the antioxidant system under Cd stress. Furthermore, it explores the mechanisms by which exogenous regulators can enhance the antioxidant capacity and mitigate Cd toxicity.

A new clinical prognosis model for breast cancer with ADSS as the hub gene.

Background: Breast cancer (BRCA) is the most common malignant tumor and the leading cause of cancer death worldwide. Adenylosuccinate synthetase (ADSS) is highly expressed in BRCA and its subtypes malignant tumors and is associated with poor prognosis. Methods: By applying ROC curve, survival analysis, WGCNA, enrichment analysis, Cox regression model and other methods, this study explores the role of ADSS in BRCA and constructs a scoring model. Results: In this study, the ADSS demonstrated good diagnostic efficacy and high expression in breast cancer tissues. Further exploration of the role of ADSS in BRCA revealed that its significantly related coexpressed genes are clearly involved in biological functions and signaling pathways associated with cell proliferation and differentiation. Additionally, the ADSS-related scoring model showed a significant prognostic impact on clinical characteristics, such as metastasis to lymph nodes, and it was discovered that the ADSS score and related scoring genes may affect the immune microenvironment of BRCA patients, potentially participating in the occurrence of this disease. Conclusion: In summary, our gene expression analysis of ADSS in BRCA generated a clinical scoring model based on the ADSS that may be used to assess prognostic risk and provide potential clinical applications and rational therapeutic targets.

Racial Differences in Adoption and Outcomes of Transcarotid Artery Revascularization among High-Risk Adults with Carotid Artery Stenosis.

BACKGROUND: Differential access to new technologies may contribute to racial disparities in surgical outcomes but has not been well-studied in the treatment of carotid artery stenosis. We examined race-based differences in adoption and outcomes of transcarotid artery revascularization (TCAR) among high-risk non-Hispanic (NH) Black and NH white adults undergoing carotid revascularization. METHODS: We conducted a retrospective analysis of TCAR, transfemoral carotid artery stenting (TF-CAS), and carotid endarterectomy (CEA) procedures performed for carotid artery stenosis from January 2015 to July 2023 in the Vascular Quality Initiative. NH Black and NH white adults were included if they met Centers for Medicare & Medicaid Services high-risk criteria. Hospitals and physicians were categorized as TCAR-capable if they had previously performed at least one TCAR prior to the time of a given procedure. We fit logistic and linear regressions, adjusted a priori for common demographic, clinical, and disease characteristics, to estimate associations of race with receipt of TCAR (versus CEA or TF-CAS), and to explore associations between race, hospital and physician characteristics, and perioperative composite stroke/death/myocardial infarction. RESULTS: Of 159,471 high-risk patients undergoing revascularization for carotid artery stenosis (mean age 72 years, 38.5% female, 5.3% NH Black), 28,722 (18.0%) received TCAR, including 16.9% of NH Black adults and 18.1% of NH white adults (P < 0.001). After controlling for patient and disease characteristics, NH Black patients were less likely than NH white patients to receive TCAR (aOR 0.92, 95% CI 0.87-0.99). The use of TCAR did not vary by race among patients treated at TCAR-capable hospitals (aOR 0.98, 95% CI 0.91-1.05) or by TCAR-capable physicians (aOR 1.01, 95% CI 0.93-1.10); however, NH Black race was associated with lower odds of receiving treatment in these settings (TCAR-capable hospital: aOR 0.93 [0.88-0.98]; TCAR-capable physician: aOR 0.92 [0.87-0.98]). NH Black race was associated with higher odds of stroke/death/MI in the full cohort (aOR 1.18, 95% CI 1.03-1.36), but not in the subgroup of patients who received TCAR (aOR 0.87, 95% CI 0.56-1.34). CONCLUSIONS: TCAR attenuated racial disparities in perioperative morbidity and mortality associated with carotid revascularization, but NH Black adults were less likely than NH white adults to receive TCAR. Relatively worse access for NH Black adults to technologically-advanced treatment settings may partially explain the broader persistence of race-based differences in carotid revascularization treatment patterns and outcomes.

A novel anti-CTLA-4 nanobody-IL12 fusion protein in combination with a dendritic cell/tumour fusion cell vaccine enhances the antitumour activity of CD8+ T cells in solid tumours.

BACKGROUND: We previously developed a nanobody targeting CTLA-4 and demonstrated that it can boost antitumour T-cell responses in vitro; however, the resulting responses after the injection of T cells into cancer models are usually weak and transient. Here, we explored whether fusing our nanobody to IL-12 would enable it to induce stronger, longer-lasting T-cell immune responses after exposure to immature dendritic cell and tumour cell fusions. RESULTS: The fusion protein enhanced the response of CD8+ T cells to tumour antigens in vitro and led to stronger, more persistent immune responses after the T cells were injected into mice bearing different types of xenografts. CONCLUSION: Our in vitro and in vivo results suggest the anticancer potential of our nanobody-interleukin fusion system and support the clinical application of this fusion approach for various nanobodies.

Single-cell multi-modal integrative analyses highlight functional dynamic gene regulatory networks directing human cardiac development.

Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrate in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks (GRNs) and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly reveal divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways. High-throughput functional genomic screens identify key transcription factors from inferred GRNs that are functionally relevant for cardiomyocyte lineages derived from each pathway. Notably, we discover a critical heat shock transcription factor 1 (HSF1)-mediated cardiometabolic GRN controlling cardiac mitochondrial/metabolic function and cell survival, also observed in fetal human cardiomyocytes. Overall, these multi-modal genomic studies enable the systematic discovery and validation of coordinated GRNs and transcriptional regulators controlling the development of distinct human cardiomyocyte populations.

Molecular Indicator for Distinguishing Multi-drug-Resistant Tuberculosis from Drug Sensitivity Tuberculosis and Potential Medications for Treatment.

The issue of multi-drug-resistant tuberculosis (MDR-TB) presents a substantial challenge to global public health. Regrettably, the diagnosis of drug-resistant tuberculosis (DR-TB) frequently necessitates an extended period or more extensive laboratory resources. The swift identification of MDR-TB poses a particularly challenging endeavor. To identify the biomarkers indicative of multi-drug resistance, we conducted a screening of the GSE147689 dataset for differentially expressed genes (DEGs) and subsequently conducted a gene enrichment analysis. Our analysis identified a total of 117 DEGs, concentrated in pathways related to the immune response. Three machine learning methods, namely random forest, decision tree, and support vector machine recursive feature elimination (SVM-RFE), were implemented to identify the top 10 genes according to their feature importance scores. A4GALT and S1PR1, which were identified as common genes among the three methods, were selected as potential molecular markers for distinguishing between MDR-TB and drug-susceptible tuberculosis (DS-TB). These markers were subsequently validated using the GSE147690 dataset. The findings suggested that A4GALT exhibited area under the curve (AUC) values of 0.8571 and 0.7121 in the training and test datasets, respectively, for distinguishing between MDR-TB and DS-TB. S1PR1 demonstrated AUC values of 0.8163 and 0.5404 in the training and test datasets, respectively. When A4GALT and S1PR1 were combined, the AUC values in the training and test datasets were 0.881 and 0.7551, respectively. The relationship between hub genes and 28 immune cells infiltrating MDR-TB was investigated using single sample gene enrichment analysis (ssGSEA). The findings indicated that MDR-TB samples exhibited a higher proportion of type 1 T helper cells and a lower proportion of activated dendritic cells in contrast to DS-TB samples. A negative correlation was observed between A4GALT and type 1 T helper cells, whereas a positive correlation was found with activated dendritic cells. S1PR1 exhibited a positive correlation with type 1 T helper cells and a negative correlation with activated dendritic cells. Furthermore, our study utilized connectivity map analysis to identify nine potential medications, including verapamil, for treating MDR-TB. In conclusion, our research identified two molecular indicators for the differentiation between MDR-TB and DS-TB and identified a total of nine potential medications for MDR-TB.

Enhancing Electrospinnability of Chitosan Membranes in Low-Humidity Environments by Sodium Chloride Addition.

The electrospinning of pure chitosan nanofibers is highly sensitive to environmental humidity, which limits their production consistency and applicability. This study investigates the addition of sodium chloride (NaCl) to chitosan solutions to enhance spinnability and mitigate the effigurefects of low humidity. NaCl was incorporated into the electrospun chitosan solution, leading to increased conductivity and decreased viscosity. These modifications improved the electrospinning process. Comparative analyses between chitosan membranes (CM) and sodium-chloride-added chitosan membranes (SCM) revealed no significant differences in chemical structure, mechanical strength, or in vitro cell proliferation. This indicates that the addition of 1% (w/v) NaCl does not adversely affect the fundamental properties of the chitosan membranes. The findings demonstrate that NaCl addition is a viable strategy for producing electrospun chitosan nanofibers in low-humidity environments, maintaining their physicochemical properties while enhancing spinnability.

[Changes in Physical Fractions within Soil Aggregates Under Nitrogen Reduction and Film Mulching Measures in Dryland Wheat Field].

We studied the changes in various physical fractions within aggregates in the arid plateau of southern Shanxi Province, which has great significance for synergistically improving soil fertility and crop productivity in this region. Bulk soil samples were collected from 0-20 cm layers during a 7-year long-term experiment in Hongtong County, Shanxi Province. Wheat grain yields, SOC concentrations, proportions, and OC contents within soil aggregates were analyzed. OC contents included： unprotected coarse particulate organic carbon within macroaggregate （M-cPOC） and fine particulate organic carbon within macroaggregate （M-fPOC）, physically protected intra-aggregate particulate organic carbon within macroaggregate （M-iPOC）, chemically/biochemically protected mineral organic carbon within macroaggregate （M-MOC）, unprotected fine particulate organic carbon within microaggregate （m-fPOC）, physically protected intra-aggregate particulate organic carbon within microaggregate （m-iPOC）, and chemically/biochemically protected mineral organic carbon within microaggregate （m-MOC）. The treatments were ① farmer fertilization （FP）, ② nitrogen reduction monitoring and control fertilization （MF）, ③ nitrogen reduction monitoring and control fertilization plus ridge film and furrow sowing （RF）, and ④ nitrogen reduction monitoring and control fertilization plus flat film hole sowing （RF）. The results showed that compared with that in the FP treatment, MF reduced SOC concentration while maintaining wheat grain yield, RF and FH synergistically improved soil fertility and crop yield, especially for the FH with SOC concentration, and wheat grain yield increased by 8.44% and 48.86%, respectively. MF significantly reduced the content of M-cPOC, RF significantly increased the content of M-iPOC, and FH significantly increased the contents of M-fPOC, M-iPOC, M-MOC, and m-iPOC by 64.00%, 98.39%, 6.16%, and 17.48%, respectively. In addition, combined with redundancy analysis, we found that the M-iPOC fraction played a major role in increasing SOC concentration and wheat grain yield, with a contribution rate of 61.5%. Therefore, the contribution of macroaggregates to soil fertility and crop productivity was higher than that of microaggregates in the arid plateau area of southern Shanxi, and flat film hole sowing could increase the content of M-iPOC, thereby synergistically increasing SOC sequestration and wheat grain yield, which could promote this cultivation technology in the region and even in the country's arid agricultural areas.