3D­printed template­guided iodine­125 seed implantation to treat complete occlusion of the superior vena cava in pulmonary sarcomatoid carcinoma: A case report.

Pulmonary sarcomatoid carcinoma (PSC), which is a type of non-small-cell lung carcinoma (NSCLC), is characterized by a high degree of malignancy, poor differentiation and a high incidence of pulmonary malignancy. In addition, PSC has a stronger invasive ability than other types of NSCLC and is not sensitive to radiation or chemotherapy. Furthermore, 90% of PSC cases exhibit vascular invasion; therefore, there is a risk of multiple metastases to the lung, bone, adrenal glands and brain, and consequently a poor prognosis, in the early stage. Targeted therapy and immunotherapy currently offer a new treatment direction; however, there have not been any significant advances in localized treatment in recent years. Thus, there is an urgent need for new localized treatment strategies. The present study describes the case of a 65-year-old man with recurrence of PSC after multi-line treatment with chemotherapy, radiotherapy, gamma knife and argon-helium knife treatment. In addition, the patient developed superior vena cava syndrome, and exhibited severe compression of the superior vena cava, chest discomfort, dyspnea and severe facial edema after chemotherapy, local gamma knife therapy (35 Gy, delivered through 14 2.5-Gy doses), argon-helium knife therapy and radiation therapy (28 Gy, delivered through seven 4-Gy doses). Partial remission was achieved after local implantation of iodine-125 (I125) seed under the guidance of a 3D-printed template, with progression-free survival observed up to 8 months afterwards. In conclusion, in patients with PSC who develop superior vena cava blockage after numerous treatment regimens, salvage I125 brachytherapy with a 3D-printed template may be suitable, and may improve local control and symptoms.

Preoperative markers for identifying CT ≤2 cm solid nodules of lung adenocarcinoma based on image deep learning.

BACKGROUND: The solid pattern is a highly malignant subtype of lung adenocarcinoma. In the current era of transitioning from lobectomy to sublobar resection for the surgical treatment of small lung cancers, preoperative identification of this subtype is highly important for patient surgical approach selection and long-term prognosis. METHODS: A total of 1489 patients with clinical stage IA1-2 primary lung adenocarcinoma were enrolled. Based on patient clinical characteristics and lung imaging features obtained via deep learning, highly correlated diagnostic factors were identified through LASSO regression and decision tree analysis. Subsequently, a logistic model and nomogram were constructed. A restricted cubic spline (RCS) was used to calculate the optimal inflection point of quantitative data and the differences between the groups. RESULTS: The three-dimensional proportion of solid component (PSC), sex, and smoking status was identified as being highly correlated diagnostic factors for solid predominant adenocarcinoma. The logistic model had good prediction efficiency, and the area under the ROC curve was 0.85. Decision curve analysis demonstrated that the application of diagnostic factors can improve patient outcomes. RCS analysis indicated that the proportion of solid adenocarcinomas increased by 4.6 times when the PSC was ≥72%. A PSC of 72% is a good cutoff point. CONCLUSION: The preoperative diagnosis of solid-pattern adenocarcinoma can be confirmed by typical imaging features and clinical characteristics, assisting the thoracic surgeon in developing a more precise surgical plan.

Wild rodents in three provinces of China exhibit a wide range of Enterocytozoon bieneusi diversity.

Introduction: Enterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite's transmission to humans and domestic animals. Methods: The present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates). Results: Among the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence. Discussion: Remarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.

Tracking tantalum stocks and flows in China from 2000 to 2021: A material flow analysis.

Tantalum is not only one of the critical metals applied in various advanced industries such as electronics, aerospace, military, and medical applications, but also is considered a conflict mineral, posing a threat to its global supply security. China plays a significant role in the tantalum industrial chain; however, the complete picture of its anthropogenic tantalum cycle remains unknown. This study investigates the tantalum cycles in China from 2000 to 2021 by conducting a dynamic material flow analysis. The results reveal that China's domestic tantalum consumption surged from 91 tons in 2000 to 580 tons in 2021. China heavily relied on importing tantalum minerals to support its domestic production, with a trade dependence rate of 90 %. Moreover, the trade volume of tantalum-related commodities experienced substantial growth from 2000 to 2014 and then fluctuated, with tantalum concentrates as the primary imported goods and electronic products as the primary exported goods. Approximately 24.9 % of the overall tantalum demand was met with secondary tantalum, in which 80 % of such secondary material being recovered during the refining and production stages. Policy recommendations are proposed accordingly, including diversifying tantalum mineral resources and increasing the recovery rates from end-of-life products. These policies can significantly contribute to achieving sufficient tantalum supply and maintaining sustainable tantalum supply chain in China.

Metabolic and Antioxidant Responses of Different Control Methods to the Interaction of Sorghum sudangrass hybrids-Colletotrichum boninense.

Colletotrichum boninense is the main pathogenic fungus causing leaf spot disease in Sorghum sudangrass hybrids, which seriously impairs its quality and yield. In order to find an efficient and green means of control, this study used the agar disk diffusion method to screen for a fungicide with the strongest inhibitory effect on C. boninense from among several bacteria, fungi, and chemicals. Then, the changes in the plant's antioxidant system and metabolic levels after treatment were used to compare the three means of control. The lowest inhibitory concentration of Zalfexam was 10 mg/mL, at which point C. boninense did not grow, and the inhibition rates of Bacillus velezensis (X7) and Trichoderma harzianum were 33.87-51.85% and 77.86-80.56%, respectively. Superoxide dismutase (SOD) and chitinase were up-regulated 2.43 and 1.24 folds in the Trichoderma harzianum group (M group) and SOD activity was up-regulated 2.2 folds in the Bacillus velezensis group (X7 group) compared to the control group (CK group). SOD, peroxidase (POD), and chitinase activities were elevated in the Zalfexam group (HX group). The differential metabolites in different treatment groups were mainly enriched in amino acid metabolism and production, flavonoid production, and lipid metabolism pathways. Compared with the diseased plants (ZB group), the M, X7, HX, and CK groups were co-enriched in the tryptophan metabolic pathway and glutamate-arginine metabolic pathway, and only the CK group showed a down-regulation of the metabolites in the two common pathways, while the metabolites of the common pathways were up-regulated in the M, X7, and HX groups. In addition, the salicylic acid-jasmonic acid pathway and ascorbic acid-glutathione, which were unique to the M group, played an important role in helping Sorghum sudangrass hybrids to acquire systemic resistance against stress. This study fills the gap in the control of Colletotrichum boninene, which causes leaf spot disease in Sorghum sudangrass hybrids. This paper represents the first reported case of biological control for leaf spot disease in Sorghum sudangrass hybrids and provides a reference for the control of leaf spot disease in Sorghum sudangrass hybrids as well as other crops infected with Colletotrichum boninense.

Promotion of maturation in CDM3-induced embryonic stem cell-derived cardiomyocytes by palmitic acid.

BACKGROUND: Myocardial infarction leads to myocardial necrosis, and cardiomyocytes are non-renewable. Fatty acid-containing cardiomyocyte maturation medium promotes maturation of stem cell-derived cardiomyocytes. OBJECTIVE: To study the effect palmitic acid on maturation of cardiomyocytes derived from human embryonic stem cells (hESCs) to optimize differentiation for potential treatment of myocardial infarction by hESCs. METHODS: hESCs were differentiated into cardiomyocytes using standard chemically defined medium 3 (CDM3). Up to day 20 of differentiation, 200 Mm palmitic acid were added, and then the culture was continued for another 8 days to mimic the environment in which human cardiomyocytes mainly use fatty acids as the main energy source. Light microscopy, transmission electron microscopy, immunofluorescence, reverse transcription-polymerase chain reaction, and cellular ATP assays, were carried out to analyze the expression of relevant cardiomyocyte-related genes, cell morphology, metabolism levels, and other indicators cardiomyocyte maturity. RESULTS: Cardiomyocytes derived from hESCs under exogenous palmitic acid had an elongated pike shape and a more regular arrangement. Sarcomere stripes were clear, and the cells color was clearly visible. The cell perimeter and elongation rate were also increased. Myogenic fibers were abundant, myofibrillar z-lines were regularly, the numbers of mitochondria and mitochondrial cristae were higher, more myofilaments were observed, and the structure of round-like discs was occasionally seen. Expression of mature cardiomyocyte-associated genes TNNT2, MYL2 and MYH6, and cardiomyocyte-associated genes KCNJ4, RYR2,and PPARα, was upregulated (p < 0.05). Expression of MYH7, MYL7, KCND2, KCND3, GJA1 and TNNI1 genes was unaffected (p > 0.05). Expression of mature cardiomyocyte-associated sarcomere protein MYL2 was significantly increased (p < 0.05), MYH7 protein expression was unaffected (p > 0.05). hESC-derived cardiomyocytes exposed to exogenous palmitic acid produced more ATP per unit time (p < 0.05). CONCLUSION: Exogenous palmitic acid induced more mature hESC-CMs in terms of the cellular architecture, expression of cardiomyocyte maturation genes adnprotein, and metabolism.

Moxibustion with seed-size moxa cones alleviates colonic injury in mice with ulcerative colitis by regulating TLR4/MyD88/NF-κB signaling pathway. / 麦粒灸调控TLR4/MyD88/NF-κBä¿¡å·é€šè·¯å‡è½»æºƒç–¡æ€§ç»“è‚ ç‚Žå°é¼ ç»“è‚ æŸä¼¤çš„æœºåˆ¶ç ”ç©¶.

OBJECTIVES: To observe the effect of moxibustion with seed-size moxa cones on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transcription factor-κB(NF-κB) signaling pathway in mice with ulcerative colitis(UC), so as to explore the therapeutic mechanism of moxibustion with seed-size moxa cones on colonic injury in UC. METHODS: Forty male C57BL/6 mice were randomly divided into blank group, model group, moxibustion group, and western medicine group, with 10 mice in each group. The UC mouse model was established by 3% DSS solution by free drinking for 7 consecutive days. Mice in the moxibustion group were treated with seed-size moxa cones at "Zhongwan"(CV12), "Tianshu"(ST25) and "Shangjuxu"(ST37), 3 moxa cones per point, with each cone applied for approximately 30 s, while mice in the western medicine group were orally administered with 300 mg/kg mesalazine solution, which were both conducted once a day for 7 consecutive days. The general condition of mice was observed every 2 days, and the disease activity index (DAI) score was calculated. HE staining was used to observe the morphology of colonic tissue in mice. ELISA was used to detect the serum interleukin(IL)-1ß, tumor necrosis factor(TNF)-α, IL-6, and IL-8 contents. Immunohistochemistry was used to detect the positive expression of TLR4 and MyD88 in colonic tissue of mice. Real-time fluorescence quantitative PCR was used to detect the expression levels of TLR4, MyD88, and NF-κB p65 mRNAs in colonic tissue. RESULTS: Compared with the blank group, varying degrees of soft or watery stools were observed, colon length and body weight were decreased(P<0.01) in mice of the model group, while DAI score, colon weight index, mucosal damage score, colonic pathological score, serum IL-1ß, TNF-α, IL-6, and IL-8 contents, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were increased(P<0.01). Compared with the model group, improved fecal characteristics were observed, colon length and body weight were increased(P<0.01) in mice of the moxibustion group and western medicine group, while DAI scores, colon weight indexes, mucosal damage scores, colonic pathological score, serum contents of IL-1ß, TNF-α, IL-6, and IL-8, positive expressions of TLR4 and MyD88, and TLR4, MyD88, and NF-κB p65 mRNA expressions in colonic tissue were decreased(P<0.01, P<0.05). There was no significant difference in the above indicators between the moxibustion group and the western medicine group. CONCLUSIONS: Moxibustion with seed-size moxa cones may alleviate colonic injury in UC mice by regulating the TLR4/MyD88/NF-κB signaling pathway and reducing the release of inflammatory factors.

Effect of immunochemotherapy infusion timing, sequence, and interval on prognosis of advanced esophageal cancer: A retrospective cohort study.

OBJECTIVE: The present study aims to explore the roles of infusion time, administration sequence and interval of immunochemotherapy (IO) in predicting overall survival (OS) in patients with locally advanced ESCC. METHODS: This multi-center retrospective study enrolled advanced ESCC who received IO between Nov 2019 and Nov 2021. Patients were divided into groups according to the three classifiers (IO infusion time, administration sequence, and infusion interval), and were further analyzed for the roles of these classifiers in predicting the prognosis of the ESCC patients. RESULTS: A total of 183 eligible patients with locally advanced ESCC were included in this study. Patients who received ≥ 75% of immunotherapy drug infusions after 12:00 h had better OS compared to those who received < 75% of immunotherapy drug infusions after 12:00 h in the 1:1 propensity score matching analysis (HRadjusted: 0.38, 95% CI: 0.17-0.82; P = 0.013). Cox proportional hazards regression revealed that ESCC patients with shorter infusion interval (< 3.3 h) had better OS (HRadjusted: 0.34, 95% CI: 0.15-0.76; P = 0.008). CONCLUSION: For patients with ESCC, the OS is significantly better when immunotherapy was administered after 12:00 h. A shorter infusion interval (< 3.3 hours) on the same-day immunochemotherapy could lead to a better prognosis.

[Exploration of JI Laixi's academic thought of acupuncture and moxibustion in clinical practice].

The paper summarizes Professor JI Laixi's academic thought on acupuncture and moxibustion. Professor JI Laixi inherits and carries forward the theory and technical system of Shanxi "new nine needles", deepens its academic connotation, and promotes clinical practice. He advocates the integration of Chinese and western medicine, and the inclusion of multiple disciplines, e.g. acupuncture and moxibustion of Chinese medicine and modern anatomy. He takes the lead in proposing a new approach to the treatment of meridian diseases of limbs, "treating the neck region for the diseases of head, treating the abdominal region for the diseases of the lumbar region, and treating the lumbar region for the disease of knees". He proposes the acupoint prescription being standardized and simplified, explores the system of acupoint prescription and establishes the prescriptions for gastric diseases, intestinal diseases and antihypertension.

Recurrent myocardial infarction in a patient with median arcuate ligament syndrome: a case report and literature review.

Median arcuate ligament (MAL) syndrome, otherwise known as celiac artery compression syndrome, is rare and is characterized by celiac artery compression by the median arcuate ligament. We report a unique case of MAL syndrome with recurrent myocardial infarction as the primary manifestation, and offer new pathophysiological insights. A man in his early 50s experienced recurrent upper abdominal pain, electrocardiographic changes, and elevated troponin concentrations, which suggested myocardial infarction. Contrast-enhanced computed tomography showed considerable celiac artery stenosis due to MAL syndrome. The patient was diagnosed with MAL syndrome and acute myocardial infarction. He declined revascularization owing to economic constraints, and opted to have conservative treatment with Chinese herbal extracts and medications. He succumbed to sudden cardiac death during a subsequent abdominal pain episode. The findings from this case show that MAL syndrome can present with recurrent myocardial infarction rather than typical intestinal angina symptoms. The pathophysiological link may involve intestinal and cardiac ischemia. An accurate diagnosis and appropriate management of MAL syndrome require careful evaluation and investigation.

Engineering an Ancestral Glycosyltransferase for Biosynthesis of 2-Phenylethyl-ß-d-Glucopyranoside and Salidroside.

Phenylethanoid glycosides (PhGs) are naturally occurring glycosides derived from plants with various biological activities. Glycosyltransferases catalyze the production of PhGs from phenylethanols via a transglycosylation reaction. The low activity and stability of glycosyltransferase limit its industrial application. An ancestral glycosyltransferase, UGTAn85, with heat resistance, alkali resistance, and high stability was resurrected using ancestral sequence reconstruction technology. This enzyme can efficiently convert phenylethanols to PhGs. The optimal reaction temperature and pH for UGTAn85 were found to be 70 °C and pH 10.0, respectively. This study employed a combination of structure-guided rational design and co-evolution analysis to enhance its catalytic activity. Potential mutation sites were identified through computer-aided design, including homology modeling, molecular docking, Rosetta dock design, molecular dynamics simulation, and co-evolution analysis. By targeted mutagenesis, the UGTAn85 mutant Q23E/N65D exhibited a 2.2-fold increase in enzyme activity (11.85 U/mg) and elevated affinity (Km = 0.11 mM) for 2-phenylethanol compared to UGTAn85. Following a fed-batch reaction, 36.16 g/L 2-phenylethyl-ß-d-glucopyranoside and 51.49 g/L salidroside could be produced within 24 h, respectively. The findings in this study provide a new perspective on enhancing the stability and activity of glycosyltransferases, as well as a potential biocatalyst for the industrial production of PhGs.

Ultrahigh Néel Temperature Antiferromagnetism and Ultrafast Laser-Controlled Demagnetization in a Dirac Nodal Line MoB3 Monolayer.

Two-dimensional (2D) antiferromagnetic (AFM) materials boasting a high Néel temperature (TN), high carrier mobility, and fast spin response under an external field are in great demand for efficient spintronics. Herein, we theoretically present the MoB3 monolayer as an ideal 2D platform for AFM spintronics. The AFM MoB3 monolayer features a symmetry-protected, 4-fold degenerate Dirac nodal line (DNL) at the Fermi level. It demonstrates a high magnetic anisotropy energy of 865 µeV/Mo and an ultrahigh TN of 1050 K, one of the highest recorded for 2D AFMs. Importantly, we reveal the ultrafast demagnetization of AFM MoB3 under laser irradiation, which induces a rapid transition from a DNL semimetallic state to a metallic state on the time scale of hundreds of femtoseconds. This work presents an effective method for designing advanced spintronics using 2D high-temperature DNL semimetals and opens up a new idea for ultrafast modulation of magnetization in topological semimetals.

Analysis of vascular thrombus and clinicopathological factors in prognosis of gastric cancer: A retrospective cohort study.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors in the world, and its prognosis is closely related to many factors. In recent years, the incidence of vascular thrombosis in patients with GC has gradually attracted increasing attention, and studies have shown that it may have a significant impact on the survival rate and prognosis of patients. However, the specific mechanism underlying the association between vascular thrombosis and the prognosis of patients with GC remains unclear. AIM: To analyze the relationships between vascular cancer support and other clinicopathological factors and their influence on the prognosis of patients with GC. METHODS: This study retrospectively analyzed the clinicopathological data of 621 patients with GC and divided them into a positive group and a negative group according to the presence or absence of a vascular thrombus. The difference in the 5-year cumulative survival rate between the two groups was compared, and the relationships between vascular cancer thrombus and other clinicopathological factors and their influence on the prognosis of patients with GC were analyzed. RESULTS: Among 621 patients with GC, the incidence of vascular thrombi was 31.7% (197 patients). Binary logistic regression analysis revealed that the degree of tumor differentiation, depth of invasion, and extent of lymph node metastasis were independent influencing factors for the occurrence of vascular thrombi in GC patients (P < 0.01). The trend of the χ 2 test showed that the degree of differentiation, depth of invasion, and extent of lymph node metastasis were linearly correlated with the percentage of vascular thrombi in GC patients (P < 0.01), and the correlation between lymph node metastasis and vascular thrombi was more significant (r = 0.387). Univariate analysis revealed that the 5-year cumulative survival rate of the positive group was significantly lower than that of the negative group (46.7% vs 73.3%, P < 0.01). Multivariate analysis revealed that age, tumor diameter, TNM stage, and vascular thrombus were independent risk factors for the prognosis of GC patients (all P < 0.05). Further stratified analysis revealed that the 5-year cumulative survival rate of stage III GC patients in the thrombolase-positive group was significantly lower than that in the thrombolase-negative group (36.1% vs 51.4%; P < 0.05). CONCLUSION: Vascular cancer status is an independent risk factor affecting the prognosis of patients with GC. The combination of vascular cancer suppositories and TNM staging can better judge the prognosis of patients with GC and guide more reasonable treatment.

Adaptive Security Control Using Output Only for Quantized Nonlinear Systems Under Irregularly Intermittent DoS Attacks.

Quantized signal-driven control for nonlinear systems is of special interest in practice. However, it is nontrivial in the presence of mismatched uncertainties and intermittent denial of service (DoS) attacks. The underlying problem becomes even more complicated when both the input and output signals are attacked, rendering the state variables and the input signal inaccessible or unavailable for the control design. Only the quantized (and thus nondifferentiable) output signal is available in the absence of attack, making regular backstepping design inapplicable. This article introduces a novel adaptive output feedback control method to tackle the aforementioned challenges. First, we design a gain-switched quantized observer to estimate the unmeasurable state variables. Second, by employing a first-order dynamic filtering technique, we circumvent the nondifferentiability issue of virtual controller arising from the signal quantization. Third, we establish design conditions for the controller parameters. Fourth, we utilize a more comprehensive sector quantizer and develop adaptive estimators to deal with the unknown quantization parameters. Finally, we demonstrate that with the proposed control method, all the closed-loop signals are semiglobally uniformly ultimately bounded (SUUB), and the regulation error can be made small enough by appropriately tuning the design parameters. Numerical simulations confirm the efficacy of the proposed approach.

Adhesion-Controlled Heterogeneous Nucleation of Tin Halide Perovskites for Eco-Friendly Indoor Photovoltaics.

The rapid development of the Internet of Things (IoT) has accelerated the advancement of indoor photovoltaics (IPVs) that directly power wireless IoT devices. The interest in lead-free perovskites for IPVs stems from their similar optoelectronic properties to high-performance lead halide perovskites, but without concerns about toxic lead leakage in indoor environments. However, currently prevalent lead-free perovskite IPVs, especially tin halide perovskites (THPs), still exhibit inferior performance, arising from their uncontrollable crystallization. Here, a novel adhesive bonding strategy is proposed for precisely regulating heterogeneous nucleation kinetics of THPs by introducing alkali metal fluorides. These ionic adhesives boost the work of adhesion at the buried interface between substrates and perovskite film, subsequently reducing the contact angle and energy barrier for heterogeneous nucleation, resulting in high-quality THP films. The resulting THP solar cells achieve an efficiency of 20.12% under indoor illumination at 1000 lux, exceeding all types of lead-free perovskite IPVs and successfully powering radio frequency identification-based sensors.

Soybean symbiotic-nodule zonation and cell differentiation are defined by NIN2 signaling and GH3-dependent auxin homeostasis.

Symbiotic nodules comprise two classes, indeterminate and determinate, defined by the presence/absence of apical meristem and developmental zonation. Why meristem and zonation are absent from determinate nodules remains unclear. Here, we define cell types in developing soybean nodules, highlighting the undifferentiated infection zones and differentiated nitrogen-fixation zones. Auxin governs infection zone maintenance. GRETCHEN HAGEN 3 (GH3) enzymes deactivate auxin by conjugation and promote cell differentiation. gh3 mutants increased undifferentiated cells and enlarged infection zones. The central symbiosis-transcription factor NIN2a activates GH3.1 to reduce auxin levels and facilitates cell differentiation. High auxin promotes NIN2a protein accumulation and enhances signaling, further deactivating auxin and depleting infection zones. Our findings shed light on the NIN2a-GH3-auxin module that drives soybean nodule cell differentiation. This study challenges our understanding of determinate nodule development and proposes that the regulation of nodule zonation offers valuable insights into broader mechanisms of cell differentiation across plant species.

MEFFGRN: Matrix enhancement and feature fusion-based method for reconstructing the gene regulatory network of epithelioma papulosum cyprini cells by spring viremia of carp virus infection.

Gene regulatory networks (GRNs) are crucial for understanding organismal molecular mechanisms and processes. Construction of GRN in the epithelioma papulosum cyprini (EPC) cells of cyprinid fish by spring viremia of carp virus (SVCV) infection helps understand the immune regulatory mechanisms that enhance the survival capabilities of cyprinid fish. Although many computational methods have been used to infer GRNs, specialized approaches for predicting the GRN of EPC cells following SVCV infection are lacking. In addition, most existing methods focus primarily on gene expression features, neglecting the valuable network structural information in known GRNs. In this study, we propose a novel supervised deep neural network, named MEFFGRN (Matrix Enhancement- and Feature Fusion-based method for Gene Regulatory Network inference), to accurately predict the GRN of EPC cells following SVCV infection. MEFFGRN considers both gene expression data and network structure information of known GRN and introduces a matrix enhancement method to address the sparsity issue of known GRN, extracting richer network structure information. To optimize the benefits of CNN (Convolutional Neural Network) in image processing, gene expression and enhanced GRN data were transformed into histogram images for each gene pair respectively. Subsequently, these histograms were separately fed into CNNs for training to obtain the corresponding gene expression and network structural features. Furthermore, a feature fusion mechanism was introduced to comprehensively integrate the gene expression and network structural features. This integration considers the specificity of each feature and their interactive information, resulting in a more comprehensive and precise feature representation during the fusion process. Experimental results from both real-world and benchmark datasets demonstrate that MEFFGRN achieves competitive performance compared with state-of-the-art computational methods. Furthermore, study findings from SVCV-infected EPC cells suggest that MEFFGRN can predict novel gene regulatory relationships.

Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments.

BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.

Circulating circ_0069094 is Correlated with the Present and Endothelial Injury of Acute Coronary Syndrome.

To investigate the impacts of circ_0069094 on acute coronary syndrome. Real-time polymerase chain reaction was used to detect the expression levels of circ_0069094, and its diagnostic performance was evaluated using ROC curve. Spearman's method was performed for correlation analysis. The levels of SOD, MDA, vWF in ACS rat models were assessed by commercial kits. The activities of H/R cell models were detected by CCK-8, Transwell, flow cytometry. The GO and KEGG were performed to analyze the function of targeted genes of miR-484. The concentration of circ_0069094 was decreased in patients with ACS, ACS rat models and H/R HUVEC models. The dysfunction of SOD, MDA, vWF, LVIDs, LVDD, and LVEF in the ACS models was regulated by the increase of circ_0069094. The viability, migration, apoptosis of the H/R models were regulated by circ_0069094. MiR-484 was a ceRNA of circ_0069094 and mediated the function of circ_0069094.

Structure-based design, synthesis, and biological characterization of indolylarylsulfone derivatives as novel human immunodeficiency virus type 1 inhibitors with potent antiviral activities and favorable drug-like profiles.

In the current antiretroviral landscape, continuous efforts are still needed to search for novel chemotypes of human immunodeficiency virus type 1 (HIV-1) inhibitors with improved drug resistance profiles and favorable drug-like properties. Herein, we report the design, synthesis, biological characterization, and druggability evaluation of a class of non-nucleoside reverse transcriptase inhibitors. Guided by the available crystallographic information, a series of novel indolylarylsulfone derivatives were rationally discovered via the substituent decorating strategy to fully explore the chemical space of the entrance channel. Among them, compound 11h bearing the cyano-substituted benzyl moiety proved to be the most effective inhibitor against HIV-1 wild-type and mutant strains (EC50 = 0.0039-0.338 µM), being far more potent than or comparable to etravirine and doravirine. Besides, 11h did not exhibit cytotoxicity at the maximum test concentration. Meanwhile, the binding target of 11h was further confirmed to be reverse transcriptase (IC50 = 0.055 µM). Preliminary structure-activity relationship were discussed to guide further optimization work. Molecular docking and dynamics simulation studies were investigated in detail to rationalize the biological evaluation results. Further drug-likeness assessment indicated that 11h possessed excellent physicochemical properties. Moreover, no apparent hERG blockade liability and cytochrome P450 inhibition were observed for 11h. Notably, 11h was characterized by favorable in vitro metabolic stability with moderate clearance rates and long half-lives in human plasma and liver microsomes. Overall, 11h holds great promise as an ideal Anti-HIV-1 lead compound due to its potent antiviral efficacy, low toxicity, and favorable drug-like profiles.