Amygdala-Targeted Relief of Neuropathic Pain: Efficacy of Repetitive Transcranial Magnetic Stimulation in NLRP3 Pathway Suppression.

This study investigates the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacological approach to treating neuropathic pain (NP), a major challenge in clinical research. Conducted on male Sprague-Dawley rats with NP induced through chronic constriction injury of the sciatic nerve, the research assessed pain behaviors and the impact of rTMS on molecular interactions within the amygdala. Through a comprehensive analysis involving Mechanical Withdrawal Threshold (MWT), Thermal Withdrawal Latency (TWL), RNA transcriptome sequencing, RT-qPCR, Western blotting, immunofluorescence staining, and Co-Immunoprecipitation (Co-IP), the study focused on the expression and interaction of integrin αvß3 and its receptor P2X7R. Findings reveal that rTMS significantly influences the expression of integrin αvß3 in NP models, suggesting an inhibition of the NP-associated NLRP3 inflammatory pathway through the disruption of integrin αvß3-P2X7R interactions. These outcomes highlight the potential of rTMS in alleviating NP by targeting molecular interactions within the amygdala, offering a promising therapeutic avenue for managing NP.

Prediction model for hepatitis B e antigen seroconversion in chronic hepatitis B with peginterferon-alfa treated based on a response-guided therapy strategy.

BACKGROUND: Models for predicting hepatitis B e antigen (HBeAg) seroconversion in patients with HBeAg-positive chronic hepatitis B (CHB) after nucleos(t)ide analog treatment are rare. AIM: To establish a simple scoring model based on a response-guided therapy (RGT) strategy for predicting HBeAg seroconversion and hepatitis B surface antigen (HBsAg) clearance. METHODS: In this study, 75 previously treated patients with HBeAg-positive CHB underwent a 52-week peginterferon-alfa (PEG-IFNα) treatment and a 24-wk follow-up. Logistic regression analysis was used to assess parameters at baseline, week 12, and week 24 to predict HBeAg seroconversion at 24 wk post-treatment. The two best predictors at each time point were used to establish a prediction model for PEG-IFNα therapy efficacy. Parameters at each time point that met the corresponding optimal cutoff thresholds were scored as 1 or 0. RESULTS: The two most meaningful predictors were HBsAg ≤ 1000 IU/mL and HBeAg ≤ 3 S/CO at baseline, HBsAg ≤ 600 IU/mL and HBeAg ≤ 3 S/CO at week 12, and HBsAg ≤ 300 IU/mL and HBeAg ≤ 2 S/CO at week 24. With a total score of 0 vs 2 at baseline, week 12, and week 24, the response rates were 23.8%, 15.2%, and 11.1% vs 81.8%, 80.0%, and 82.4%, respectively, and the HBsAg clearance rates were 2.4%, 3.0%, and 0.0%, vs 54.5%, 40.0%, and 41.2%, respectively. CONCLUSION: We successfully established a predictive model and diagnosis-treatment process using the RGT strategy to predict HBeAg and HBsAg seroconversion in patients with HBeAg-positive CHB undergoing PEG-IFNα therapy.

Storage of plasma-derived exosomes: evaluation of anticoagulant use and preserving temperatures.

Exosomes carry large cargo of proteins, lipids, and nucleic acids, serving as versatile biomarkers for disease diagnosis and vehicles for drug delivery. However, up to date, no well recognized standard procedures for exosome storage were available for clinical application. This study aimed to determine the optimal storage conditions and the anticoagulants for plasma-derived exosome isolation. Fresh whole blood samples were collected from healthy participants and preserved in four different anticoagulants including sodium citrate (SC1/4), sodium citrate (SC1/9), lithium heparin (LH), or Ethylenediamine tetraacetic acid (EDTA), respectively. Exosomes were extracted from the plasma by differential ultracentrifugation and stored at three different temperatures, 4°C, -20°C or - 80°C for a duration ranging from one week to six months. All plasma samples for storage conditions comparison were pretreated with LH anticoagulant. Exosome features including morphological characteristics, pariticles size diameter, and surface protein profiles (TSG101, CD63, CD81, CD9, CALNEXIN) were assessed by transmission electron microscopy, Nanoparticle Tracking Analysis, and Western Blotting, respectively. Exosomes preserved in LH and SC1/4 group tended to remain intact microstructure with highly abundant protein biomarkers. Exosomes stored at 4°C for short time were prone to be more stable compared to thos at -80°C. Exosomes stored in plasma were superior in terms of ultrastructure, size diameter and surface protein expression to those stored in PBS. In conclusion, plasma-dervied exosome characteristics strictly depend on the anticoagulants and storage temperature and duration.

What is the context? Effective isolation of exosomes is a prerequisite for subsequent investigation into its involvemnt in disease development as well as potentialtherapeutic applications.Anticoagulants, storage temperature and durations might change the microscopical structure, integrity and also the stability of plasma-derived exosomes. However, no internationally recognized standard of exosome storage procedure was available for clinical use.What is new? Our finding evaluated the effect of anticoagulants and storage on plasma exosome characteristics.Exosomes isolated from plasma preserved with Li-heparin and sodium citrate (1/4) showed better physical properties and surface marker protein expression.Isolated exosomes appeared more stable in a short time for 4°C compared to −80°C. Storage of exosomes in plasma showed better physical properties and surface marker protein expression than in PBS.What is the impact? Our findings inform the significance of standardizing procedure of exosome isolation and preservation.

Transportation infrastructure upgrading and green development efficiency: Empirical analysis with double machine learning method.

In order to deal with the environmental problems such as pollution emissions and climate change, sustainable development in the field of transportation has gradually become a hot topic to all sectors of society. In addition, promoting the green and low-carbon transformation of China's transportation is also an important issue in the new era. Thus, it is particularly important to correctly identify the green effect of high-speed rail. However, the traditional causal reasoning model faces several challenges such as 'dimensional curse' and multicollinearity. Based on the panel data of 283 prefecture-level cities in China from 2003 to 2019, this study uses the double machine learning model to explore the impact of transportation infrastructure upgrading on the efficiency of urban green development in China. The research shows that the upgrading of transportation infrastructure can effectively improve the efficiency of urban green development by 4%. Service industry agglomeration and green innovation are verified as two mediating channels. Moreover, the synthetic difference in difference model is employed to evaluate the regional impact of high-speed rail, and finds that the regional impact of transportation policies often exceeds the impact of individual cities. We further apply the conclusions of this paper to the research at the micro enterprise level. Goodman-Bacon decomposition and a variety of robustness tests confirm the validity of our conclusions. The study's comprehensive empirical analysis not only validates the positive effects of transportation upgrades on green development, but also offers novel insights into the underlying mechanisms and policy implications of transportation upgrading.

Changes in the etiology of liver cirrhosis and the corresponding management strategies.

We read with interest the article by Xing Wang, which was published in the recent issue of the World Journal of Hepatology 2023; 15: 1294-1306. This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis (LC), prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma (HCC), and management strategies. The etiology of cirrhosis varies according to geographical, economic, and population factors. Viral hepatitis is the dominant cause in China. Vaccination and effective treatment have reduced the number of people with viral hepatitis, but the overall number is still large. Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage. The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease (MASLD)-associated LC and alcoholic liver disease in the future. Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development. These changing trends indicate a need for greater emphasis on tackling obesity and diabetes, and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD. In an effort to help cope with these changing trends, the authors further proposed countermeasures for healthcare authorities doctors, and patients.

Describe the morphology and mitochondrial genome of Mecidea indica Dallas, 1851 (Hemiptera, Pentatomidae), with its phylogenetic position.

We here describe the external morphology and complete mitochondrial genome characteristics of Mecidea indica Dallas, 1851, and clarify the evolutionary rate and divergence time. The M. indica mitochondrial genome length is 15,670 bp, and it exhibits a typical high A+T-skew (76.31%). The sequence shows strong synteny with the original gene arrangement of Drosophila yakuba Burla, 1954 without rearrangement. The M. indica mitochondrial genome characteristics were analyzed, and phylogenetic trees of Pentatomidae were reconstructed using Bayesian methods based on different datasets of the mitochondrial genome datasets. Phylogenetic analysis shows that M. indica belongs to Pentaotominae and form a sister-group with Anaxilaus musgravei Gross, 1976, and Asopinae is highly supported as monophyletic. Molecular clock analysis estimates a divergence time of Pentatomidae of 122.75 Mya (95% HPD: 98.76-145.43 Mya), within the Mesozoic Cretaceous; the divergence time of M. indica and A. musgravii was no later than 50.50 Mya (95% HPD: 37.20-64.80 Mya). In addition, the divergence time of Asopinae was 62.32 Mya (95% HPD: 47.08-78.23 Mya), which was in the Paleogene of the Cenozoic era. This study is of great significance for reconstructing the phylogeny of Pentatomidae and providing insights into its evolutionary history.

The bone-protective benefits of kaempferol combined with metformin by regulation of osteogenesis-angiogenesis coupling in OVX rats.

This study was to investigate the potential mechanisms of treatment with metformin (Met) combined with kaempferol (Kae) against postmenopausal osteoporosis. Experiments were conducted in both ovariectomy (OVX)-induced osteoporosis rats and in vitro using RAW264.7 cells, MC3T3-E1 cells, and HUVECs. Results demonstrated the therapeutic effect of Met combined with Kae on osteoporosis. In vivo, Kae alone and in combination with Met treatments enhanced tibial trabecular microstructure, bone mineral density (BMD), and mechanical properties in OVX rats without causing hepatotoxicity and nephrotoxicity. It also reduced bone resorption markers (CTX-1 and TRAP) and increased the bone formation marker (PINP) level in the serum of OVX rats. The expression of bone resorption marker TRAP was reduced, while bone formation markers Runx2 and ALP were enhanced in the bone tissue of OVX rats. Furthermore, Met combined with Kae also promoted the expression of angiogenesis-related markers CD31 and VEGF in OVX rats. In vitro, MC3T3-E1s cells treated with Met combined with Kae showed higher expression of ALP, Runx2, and VEGF. Interestingly, the treatment did not directly promote HUVECs migration and angiogenesis, but enhanced osteoblast-mediated angiogenesis by upregulating VEGF levels. Additionally, Met combined with Kae treatment promoted VEGF secretion in MC3T3-E1, and activated the Notch intracelluar pathway by upregulating HES1 and HEY1 in HUVECs. Meantime, their stimulation on CD31 expression were inhibited by DAPT, a Notch signaling inhibitor. Overall, this study demonstrates the positive effects of Met combined with Kae on osteoporotic rats by promoting osteogenesis-angiogenesis coupling, suggesting their potential application in postmenopausal osteoporosis.

Ultrasound-guided percutaneous high-frequency irreversible electroporation in porcine livers using four electrode needles: A feasibility and safety study.

BACKGROUND: Malignant liver tumors seriously endanger human health. Among different therapeutic approaches, high-frequency irreversible electroporation (H-FIRE) is a recently emerging tumor ablation technique. The objective of this study was to evaluate the feasibility and safety of ultrasound-guided percutaneous H-FIRE using four electrode needles in porcine livers. METHODS: Twelve experimental pigs underwent percutaneous H-FIRE ablation using a compound steep-pulse therapeutic device. Liver tissues adjacent to the gallbladder, blood vessels, and bile ducts were selected as the ablation targets. Pigs were randomly divided into three groups: (1) immediately after ablation (N = 4), (2) 2 days after ablation (N = 4), and (3) 7 days after ablation (N = 4). Blood routine, liver and kidney function, and myocardial enzyme levels were measured before and after ablation. Ultrasound, contrast-enhanced ultrasound (CEUS), contrast-enhanced magnetic resonance imaging (MRI), and hematoxylin-eosin staining were performed to evaluate the ablation performance. RESULTS: Ultrasound-guided percutaneous H-FIRE ablations using four electrode needles were successfully performed in all 12 experimental pigs. The general conditions of the pigs, including postoperative activities and feeding behaviors, were normal, with no significant changes compared with the preoperative conditions. The imaging features of ultrasound, CEUS, and MRI demonstrated no significant changes in the gallbladder walls, bile ducts, or blood vessels close to the ablation areas. Laboratory tests showed that liver function indices and myocardial enzymes increased temporarily after H-FIRE ablation, but decreased to normal levels at 7 days after ablation. Histopathological examinations of porcine liver specimens showed that this technique could effectively ablate the target areas without damaging the surrounding or internal vascular systems and gallbladder. CONCLUSIONS: This study demonstrated the feasibility and safety of ultrasound-guided percutaneous H-FIRE ablation in porcine livers in vivo, and proposed a four-needle method to optimize its clinical application.

Interaction of Biochar Addition and Nitrogen Fertilizers on Wheat Production and Nutrient Status in Soil Profiles.

To investigate the responses of crop production and soil profile nutrient status to biochar (BC) application, we conducted a soil column experiment considering two BC addition rates (0.5 and 1.5 wt% of the weight of 0-20 cm topsoil) combined with two nitrogen (N) input levels (low N: 144 kg ha-1, LN; high N: 240 kg ha-1, HN). The results showed that BC application increased the soil pH. The soil pH of the 0-10 cm profile under LN and the 20-40 cm profile under HN were both significantly increased by 0.1-0.2 units after BC addition. Under LN, BC addition significantly increased NH4+-N (17.8-46.9%), total N (15.4-38.4%), and soil organic carbon (19.9-24.0%) in the 0-10 cm profile, but decreased NH4+-N in the 20-30 cm soil profile and NO3--N in the 10-30 cm profile by 13.8-28.5% and 13.0-34.9%, respectively. BC had an increasing effect on the available phosphorus, the contents of which in the 10-20 and 30-40 cm soil profiles under LN and 20-30 cm profile under HN were significantly elevated by 14.1%, 24.0%, and 23.27%, respectively. However, BC exerted no effect on the available potassium in the soil profile. BC had a strong improving effect (15.3%) on the wheat yield, especially the N144 + BC0.5% treatment, which could be compared to the HN treatment, but there was no yield-increasing effect when high N fertilizer was supplied. In summary, BC improved the fertility of agriculture soil (0-20 cm) with wheat. In particular, low N inputs together with an appropriate rate of BC (0.5 wt%) could not only achieve the low inputs but also the high outputs in wheat production. In future study, we will compare the effects of multiple doses of N and BC on soil fertility and crop production.

Evaluating the relationship between the proportion of X-chromosome deletions and clinical manifestations in children with turner syndrome.

Purpose: Analyze the relationship between changes in the proportion of X-chromosome deletions and clinical manifestations in children with Turner syndrome (TS). Methods: X-chromosome number abnormalities in 8,635 children with growth retardation were identified using fluorescence in situ hybridization (FISH). Meanwhile, the relationship between the proportion of X-chromosome deletions and the clinical manifestations of TS, such as face and body phenotype, cardiovascular, renal, and other comorbidities in children with TS was analyzed. Results: A total of 389 children had X-chromosome number abnormalities, with an average age at diagnosis of 9.2 years. There was a significant increase in diagnoses around the ages of 3 and 7 years and highest number of diagnoses at 10 years of age. 130 with XO (complete loss of an X-chromosome), 205 with XO/XX, 8 with XO/XXX, 23 with XO/XX/XXX, 19 with XO/XY, and 4 with XO/XY/XYY. Body and facial phenotypes increased with higher mosaicism proportions, with a relatively high correlation shown with Pearson correlation analysis (r = 0.26, p = 1.7e-06). The incidence of congenital heart malformations was 25.56%, mainly involving a bicuspid aortic valve, and were more common in patients who had complete loss of an X-chromosome. However, this relationship was not present for renal disease (p = 0.26), central nervous system, thyroid, or liver disease. Conclusion: The mosaicism (XO/XX) is the most common karyotype of TS in screened cases. The phenotypes in children with TS may increase with the proportion of X-chromosome deletions, but the renal disease and comorbidities did not show the same characteristics.

Vortex-based soft magnetic composite with ultrastable permeability up to gigahertz frequencies.

Soft magnetic materials with stable permeability up to hundreds of megahertz (MHz) are urgently needed for integrated transformers and inductors, which are crucial in the more-than-Moore era. However, traditional frequency-stable soft magnetic ferrites suffer from low saturation magnetization and temperature instability, making them unsuitable for integrated circuits. Herein, we fabricate a frequency-stable soft magnetic composite featuring a magnetic vortex structure via cold-sintering, where ultrafine FeSiAl particles are magnetically isolated and covalently bonded by Al2SiO5/SiO2/Fe2(MoO4)3 multilayered heterostructure. This construction results in an ultrastable permeability of 13 up to 1 gigahertz (GHz), relatively large saturation magnetization of 105 Am2/kg and low coercivity of 48 A/m, which we ascribe to the elimination of domain walls associated with almost uniform single-vortex structures, as observed by Lorentz transmission electron microscopy and reconstructed by micromagnetic simulation. Moreover, the ultimate compressive strength has been simultaneously increased up to 337.1 MPa attributed to the epitaxially grown interfaces between particles. This study deepens our understanding on the characteristics of magnetic vortices and provides alternative concept for designing integrated magnetic devices.

Evaluation study of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy in the treatment of Chinese obese patients based on efficacy and nutrition.

To evaluate the efficacy and nutrition of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in Chinese obese patients in the first postoperative year. Clinical data of 66 obese patients who underwent SADI-S surgery at China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were retrospectively collected. The weight, body mass index (BMI), percentage of excess weight loss (%EWL), and percentage of total weight loss (%TWL) were recorded at 3, 6, and 12 months after surgery. Moreover, metabolic disease remission and nutrient deficiencies were assessed at 1 year postoperatively. Overall, 66 patients (38 males and 28 females) were recruited, with a mean age of 35 (18-61) years and an average preoperative BMI of 42.94 kg/m2. Before surgery, 38 patients had type 2 diabetes mellitus (T2DM), 46 patients had hyperuricemia (HUA), 45 patients had hypertension (HTN), 35 patients had hyperlipidemia, 12 patients had hypercholesterolemia, 12 patients had hyper-low-density lipoproteinemia, and 14 patients had gastroesophageal reflux disease symptoms (GERD). All patients had undergone a DaVinci robotic or laparoscopic SADI-S surgery, and none converted to laparotomy or died. Four patients developed postoperative complications and were cured and discharged after conservative treatment or surgical treatment. At 3, 6 and 12 months, the average %EWL was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65%, %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89%, respectively. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), uric acid (UA), triglycerides (TG), blood pressure (BP), and other indexes were significantly lower after one year post-surgery compared with the preoperative period (P < 0.05). The remission rates of T2DM, HUA, HTN, hypertriglyceridemia, hypercholesterolemia, and hyper-low-density lipoproteinemia 1 year after surgery were 100, 65.2, 62.2, 94.3, 100, and100%, respectively. One year after surgery, the remission rate of GERD was 71.4% (10/14), the rate of new occurrence of GERD was 12.1% (8/66), and the overall incidence rate was 18.2% (12/66). Except for vitamin B12(vit B12), the other nutrient indexes were significantly decreased after 1 year of surgery relative to levels before surgery (P < 0.05). The deficiency rates for vitamin A (vit A), vitamin E (vit E), zinc ion (Zn), and folic acid (FA) were higher (45.5, 25.8, 24.2, and 16.7%, respectively); however, there were no related clinical symptoms. SADI-S had significant effects on weight loss and metabolic disease remission. The main nutrient deficiencies after SADI-S were vit A, vit E, Zn, and FA deficiencies. The long-term efficacy and safety of SADI-S warrant further follow-up.

Plant size-dependent influence of foliar fungal pathogens promotes diversity through allometric growth.

The effect of pathogens on host diversity has attracted much attention in recent years, yet how the influence of pathogens on individual plants scales up to affect community-level host diversity remains unclear. Here, we assessed the effects of foliar fungal pathogens on plant growth and species richness using allometric growth theory in population-level and community-level foliar fungal pathogen exclusion experiments. We calculated growth scaling exponents of 24 species to reveal the intraspecific size-dependent effects of foliar fungal pathogens on plant growth. We also calculated the intercepts to infer the growth rates of relatively larger conspecific individuals. We found that foliar fungal pathogens inhibited the growth of small conspecific individuals more than large individuals, resulting in a positive allometric growth. After foliar fungal pathogen exclusion, species-specific growth scaling exponents and intercepts decreased, but became positively related to species' relative abundance, providing a growth advantage for individuals of abundant species with a higher growth scaling exponent and intercept compared with rare species, and thus reduced species diversity. By adopting allometric growth theory, we elucidate the size-dependent mechanisms through which pathogens regulate species diversity and provide a powerful framework to incorporate antagonistic size-dependent processes in understanding species coexistence.

Overexpression of vacuolar transporters OsVIT1 and OsVIT2 reduces cadmium accumulation in rice.

Excessive cadmium in rice grain in agricultural production is an important issue to be addressed in some southern regions of China. In this study, we constructed transgenic rice overexpressing OsVIT1 and OsVIT2 driven by 35S promoter in the cultivar ZH11. Compared with ZH11, OsVIT1 expression in leaves was significantly increased by 3-6.6 times and OsVIT2 expression in leaves was significantly increased by 2-2.5 times. Hydroponic experiments showed that overexpression of OsVIT1 and OsVIT2 increased the tolerance to Fe deficiency, significantly reduced Cd content in shoot and xylem sap, and had no effect on Cd tolerance in rice. Two years of field trials showed that the Fe content in the grain of OsVIT1 and OsVIT2 overexpressed materials was significantly reduced by 20-40% and the straw Fe content was significantly increased by 10-45%, and the grain Fe content distribution ratio was significantly decreased and the straw Fe distribution ratio was significantly increased compared with the wild type. The OsVIT1 and OsVIT2 overexpressed materials significantly reduced the Cd content of grain by 40-80% and the Cd content of straws by 37-77%, and the bioconcentration factor of Cd was significantly reduced in both grains and straw of OsVIT1 and OsVIT2 overexpressed materials. Overexpression of OsVIT1 and OsVIT2 did not affect the concentration of other metal ions in rice straw and grain. qRT-PCR analysis showed that the expression of the low affinity cation transporter OsLCT1 was significantly downregulated in the OsVIT1 and OsVIT2 overexpressed materials. In conclusion, overexpression of OsVIT1 and OsVIT2 reduced Cd accumulation in straw and grains, providing a strategy for Cd reduction in rice.

Case report: Giant lymph node metastases: a new opportunity for cancer radioimmunotherapy?

Background: Despite the significant progress made in radiotherapy and chemotherapy for the treatment of cervical cancer, patients with lymph node metastasis still have a poor prognosis. It is widely accepted that lymph node metastasis plays a crucial role in the spread of cancer to other organs and is considered an independent factor in predicting a poor prognosis. However, recent research suggests that the importance of lymph nodes in tumor therapy needs to be reevaluated, as preserving the integrity of lymph nodes before immunotherapy can enhance treatment effectiveness. Case presentation: In this report, we present two cases of advanced cervical cancer patients with giant metastatic lymph node lesions in the neck. These patients were effectively treated with a combination of local radiotherapy and immunotherapy after conventional chemoradiotherapy had failed. The combination therapy resulted in significant clinical improvements, with patient 1 achieving over 12 months of progression-free survival (PFS) and patient 2 maintaining sustained remission for an impressive 24 months. Conclusions: The combination of local radiotherapy and immunotherapy shows promise as a viable treatment option for cervical cancer patients with distant lymph node metastasis, and the giant lymph node metastases may play an important role in this process, which might provide a new opportunity for cancer radioimmunotherapy.

CircCPA4 induces ASCT2 expression to promote tumor property of non-small cell lung cancer cells in a miR-145-5p-dependent manner.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a type of lung cancer that occurs in the cells of the respiratory tract, and its development is influenced by the regulation of circular RNAs (circRNAs). However, the role of circRNA carboxypeptidase A4 (circCPA4) in the progression of NSCLC and the underlying mechanism remain relatively clear. METHODS: The study utilized both real-time quantitative polymerase chain reaction (RT-qPCR) and western blot techniques to evaluate the levels of circCPA4, microRNA-145-5p (miR-145-5p), alanine, serine, or cysteine-preferring transporter 2 (ASCT2). To assess cell proliferation, cell counting kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were performed. Apoptosis was determined using flow cytometry, while cell migration and invasive capacity were evaluated through transwell and wound-healing assays. Intracellular levels of glutamine, glutamate, and α-KG were measured using specific kits. The relationship between miR-145-5p and circCPA4 or ASCT2 was confirmed using dual-luciferase reporter assay and RNA immunoprecipitation assay. RESULTS: CircCPA4 and ASCT2 RNA levels were elevated, while miR-145-5p was downregulated in both NSCLC tissues and cells. Depletion of circCPA4 significantly inhibited NSCLC cell proliferation, migration, invasion, and intracellular levels of glutamine, glutamate, and α-KG, and promoted apoptosis. Moreover, circCPA4 knockdown delayed tumor growth in vivo. Furthermore, circCPA4 was found to bind to miR-145-5p, thereby regulating the progression of NSCLC in vitro. ASCT2 was also identified as a downstream target of miR-145-5p, and its upregulation rescued the effects of miR-145-5p overexpression on NSCLC cell processes. CONCLUSION: CircCPA4 knockdown inhibited tumor property of NSCLC cells by modulating the miR-145-5p/ASCT2 axis.

Development of efficient and economic Bi2O3/BN/Co3O4 composite photocatalyst: Degradation mechanism, pathway and toxicity study of norfloxacin.

The production of cheap, efficient, and stable photocatalysts for degrading antibiotic contaminants remains challenging. Herein, Bi2O3/boron nitride (BN)/Co3O4 ternary composites were synthesized using the impregnation method. The morphological characteristics, structural features, and photochemical properties of the prepared photocatalysts were investigated via X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscopy, high-resolution transmission electron microscopy, and ultraviolet-visible (Vis) diffuse reflectance spectrum techniques. BN was used as a charge transfer bridge in the ternary composites, which afforded a heterojunction between the two semiconductors. The formation of the heterojunction substantially enhanced the charge separation and improved the photocatalyst performance. The degradation activity of the Bi2O3/BN/Co3O4 ternary composites against norfloxacin (NOR) under Vis light irradiation was investigated. The degradation rate of NOR using 5-wt% Bi2O3/BN/Co3O4 reached 98% in 180 min, indicating excellent photocatalytic performance. The ternary composites also exhibited high photostability with a degradation efficiency of 88.4% after five cycles. Hydroxyl radicals (•OH), superoxide radicals (•O2-), and holes (h+) played a synergistic role in the photocatalytic reaction, where h+ and •O2- were more important than •OH. Consequently, seven intermediates and major photocatalytic degradation pathways were identified. Toxicity experiments showed that the toxicity of the degradation solution to Chlorella pyrenoidosa decreased. Finally, the ecotoxicity of NOR and its intermediates were analyzed using the Toxicity Estimation Software Tool, with most intermediates exhibiting low toxicity.

Biochar leachate reduces primary nitrogen assimilation by inhibiting nitrogen fixation and microbial nitrate assimilation.

Biochar contains biotoxic aromatic compounds, and their influence on nitrogen-fixing cyanobacteria, the critical nitrogen fixer in paddy soil, has never been tested. Here, the physiological, metabolomic, and transcriptomic analyses of Nostoc sp. PCC7120 in response to biochar leachate were performed. The results suggested that biochar leachate inhibited the efficiency of photosynthesis, nitrogen fixation, and nitrate assimilation activities of nitrogen-fixing cyanobacteria. Biochar leachate containing aromatic compounds and odd- and long-chain saturated fatty acids impaired the membrane structure and antenna pigments, damaged the D1 protein of the oxygen evolution complex, and eventually decreased the electron transfer chain activity of photosystem II. Moreover, the nitrogen fixation and nitrate assimilation abilities of nitrogen-fixing cyanobacteria were inhibited by a decrease in photosynthetic productivity. A decrease in iron absorption was another factor limiting nitrogen fixation efficiency. Our study highlights that biochar with relatively high contents of dissolved organic matter poses a risk to primary nitrogen assimilation reduction and ecosystem nitrogen loss. Further evidence of the potential negative effects of biochar leachates on the fixation and assimilation capacity of nitrogen by soil microbes is needed to evaluate the impact of biochar on soil multifunctionality prior to large-scale application.

Highly anisotropic Fe3C microflakes constructed by solid-state phase transformation for efficient microwave absorption.

Soft magnetic materials with flake geometry can provide shape anisotropy for breaking the Snoek limit, which is promising for achieving high-frequency ferromagnetic resonances and microwave absorption properties. Here, two-dimensional (2D) Fe3C microflakes with crystal orientation are obtained by solid-state phase transformation assisted by electrochemical dealloying. The shape anisotropy can be further regulated by manipulating the thickness of 2D Fe3C microflakes under different isothermally quenching temperatures. Thus, the resonant frequency is adjusted effectively from 9.47 and 11.56 GHz under isothermal quenching from 700 °C to 550 °C. The imaginary part of the complex permeability can reach 0.9 at 11.56 GHz, and the minimum reflection loss (RLmin) is -52.09 dB (15.85 GHz, 2.90 mm) with an effective absorption bandwidth (EAB≤-10 dB) of 2.55 GHz. This study provides insight into the preparation of high-frequency magnetic loss materials for obtaining high-performance microwave absorbers and achieves the preparation of functional materials from traditional structural materials.

Targeting RORγ inhibits the growth and metastasis of hepatocellular carcinoma.

Approximately 80%-90% of hepatocellular carcinomas (HCC) occur in a premalignant environment of fibrosis and abnormal extracellular matrix (ECM), highlighting an essential role of ECM in the tumorigenesis and progress of HCC. However, the determinants of ECM in HCC are poorly defined. Here, we show that nuclear receptor RORγ is highly expressed and amplified in HCC tumors. RORγ functions as an essential activator of the matrisome program via directly driving the expression of major ECM genes in HCC cells. Elevated RORγ increases fibronectin-1 deposition, cell-matrix adhesion, and collagen production, creating a favorable microenvironment to boost liver cancer metastasis. Moreover, RORγ antagonists effectively inhibit tumor growth and metastasis in multiple HCC xenografts and immune-intact models, and they effectively sensitize HCC tumors to sorafenib therapy in mice. Notably, elevated RORγ expression is associated with ECM remodeling and metastasis in patients with HCC. Taken together, we identify RORγ as a key player of ECM remodeling in HCC and as an attractive therapeutic target for advanced HCC.