Functional analysis of circSNYJ1/miR-142-5p/CCND1 regulatory axis in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), the most prevalent form of lung cancer, accounts for approximately 85% of all lung cancer diagnoses. Circular RNAs (circRNAs) are non-coding RNAs that play an active role in gene expression regulation, influencing cell growth, migration, and apoptosis. Here, we aimed to investigate the function of circSNYJ1 in NSCLC. In the present study, we found that circSNYJ1 expression level was increased in NSCLC tissues and cell lines. Knockdown of circSNYJ1 suppressed NSCLC cell proliferation, colony formation and migration while promoting apoptosis. Mechanistically, we demonstrated that circSNYJ1 sponged miR-142-5p, thereby regulating the expression of CCND1, a well-known cell cycle regulator. In conclusion, this study uncovered a novel circSNYJ1/miR-142-5p/CCND1 axis involved in NSCLC progression, providing potential diagnostic and prognostic biomarkers for treating NSCLC.

Exogenous microbubbles contribute to valorization of microalgal compounds by ultrasound-assisted extraction.

Ultrasound-assisted extraction (UAE) shows great potential in exploiting microalgal compounds. However, upgrading the extraction system lacks concerns. This study proposes a novel sono-reactor featuring a microbubble distributor for increasing bubble abundance and correspondingly improving microalgal compound extraction. Results indicate that protein concentrations increase with ultrasound powers and extraction time while an optimized gas flow rate exists. The optimal parameters by Box-Behnken design are power 646.0 W, nitrogen flow rate 25.0 mL/min, and time 40.0 min, with an optimal protein concentration of 249.1 mg/L - a substantial improvement over gas-free extraction. The strategic increase in bubble abundance enhances microalgal compound extraction efficiency and extraction kinetics The system innovation will contribute to the advancement of bioresource utilization and sustainability.

Random Permutation Set Reasoning.

In artificial intelligence, it is crucial for pattern recognition systems to process data with uncertain information, necessitating uncertainty reasoning approaches such as evidence theory. As an orderable extension of evidence theory, random permutation set (RPS) theory has received increasing attention. However, RPS theory lacks a suitable generation method for the element order of permutation mass function (PMF) and an efficient determination method for the fusion order of permutation orthogonal sum (POS). To solve these two issues, this paper proposes a reasoning model for RPS theory, called random permutation set reasoning (RPSR). RPSR consists of three techniques, including RPS generation method (RPSGM), RPSR rule of combination, and ordered probability transformation (OPT). Specifically, RPSGM can construct RPS based on Gaussian discriminant model and weight analysis; RPSR rule incorporates POS with reliability vector, which can combine RPS sources with reliability in fusion order; OPT is used to convert RPS into a probability distribution for the final decision. Besides, numerical examples are provided to illustrate the proposed RPSR. Moreover, the proposed RPSR is applied to classification problems. An RPSR-based classification algorithm (RPSRCA) and its hyperparameter tuning method are presented. The results demonstrate the efficiency and stability of RPSRCA compared to existing classifiers.

An Embeddable Implicit IUVD Representation for Part-Based 3D Human Surface Reconstruction.

To reconstruct a 3D human surface from a single image, it is crucial to simultaneously consider human pose, shape, and clothing details. Recent approaches have combined parametric body models (such as SMPL), which capture body pose and shape priors, with neural implicit functions that flexibly learn clothing details. However, this combined representation introduces additional computation, e.g. signed distance calculation in 3D body feature extraction, leading to redundancy in the implicit query-and-infer process and failing to preserve the underlying body shape prior. To address these issues, we propose a novel IUVD-Feedback representation, consisting of an IUVD occupancy function and a feedback query algorithm. This representation replaces the time-consuming signed distance calculation with a simple linear transformation in the IUVD space, leveraging the SMPL UV maps. Additionally, it reduces redundant query points through a feedback mechanism, leading to more reasonable 3D body features and more effective query points, thereby preserving the parametric body prior. Moreover, the IUVD-Feedback representation can be embedded into any existing implicit human reconstruction pipeline without requiring modifications to the trained neural networks. Experiments on the THuman2.0 dataset demonstrate that the proposed IUVD-Feedback representation improves the robustness of results and achieves three times faster acceleration in the query-and-infer process. Furthermore, this representation holds potential for generative applications by leveraging its inherent semantic information from the parametric body model.

Proprotein convertase subtilisin/kexin type 9 inhibitors protect against contrast-associated acute kidney injury in patients with atherosclerotic cardiovascular disease.

Background and aims: Contrast-associated acute kidney injury (CA-AKI) may occur in patients undergoing medical procedures involving x-rays and radiocontrast media, potentially resulting in prolonged renal impairment. However, no effective treatments are available. Therefore, this study aimed to investigate the efficacy of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in reducing CA-AKI incidence among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing percutaneous coronary intervention. Methods: This retrospective cohort study included patients who underwent percutaneous coronary intervention between January 2020 and December 2021 at Tianjin Chest Hospital. The study endpoint was CA-AKI incidence, and the impact of selection bias and other potential confounding factors was mitigated using bias matching. Overall, 1,642 patients were included in this study: 821 patients received evolocumab treatment before contrast agent application, and 821 did not receive such treatment. Results: CA-AKI incidence was 6.21% and 8.04% in the evolocumab and control groups, respectively. After propensity-score matching, the incidence rate was 5.09% and 14.16% in the evolocumab and control groups, respectively. Evolocumab treatment significantly reduced CA-AKI incidence (p < 0.001). Consistent findings were obtained in the subgroups of individuals with type II diabetes mellitus, chronic heart failure, and hypertension. Evolocumab exhibited a significantly greater protective effect in the high- and extremely high-risk populations than in the low- and middle-risk populations (p < 0.001). Conclusions: Evolocumab administration significantly reduced CA-AKI incidence among patients with ASCVD. Notably, this effect was more prominent within the subset of high- and extremely high-risk individuals who were already experiencing CA-AKI.

Hierarchical supramolecules composed of starch-based nanocluster aggregates with light-responsive mechanical strain for remotely rapid and precise actuation.

Hierarchical supramolecular systems, characterized by nanoscale sensitivity and macroscopic tangible changes, offer promising perspectives for the design of remotely controllable, rapid, and precise actuation materials, serving as a potential substitution for non-intelligent and complex actuation switches. Herein, we reported on the disassembly of orderly and rigid starch helical covalent structures, and their subsequent reassembly into a hierarchical supramolecular gel composed of nanocluster aggregates, integrating supramolecular interactions of three different scales. The incorporation of photo-sensitive FeIIITA, a complex of trivalent iron ions and tannic acid, significantly enhances the photo-responsive strain capacity of the hierarchical supramolecular gel. The supramolecular gel exhibits its features in a rapid light-responsive rate of hardness and viscosity, enabling the actuation of objects within 22 s under light exposure when employed as a remote actuation switch. Meanwhile, this actuation mechanism of the hierarchical supramolecular gel also has a promising perspective in precise control, identifying and actuating one of the two objects in distances of 0.8 mm even smaller scales. Our work provides a reliable reference for replacing complex actuation switches with intelligent materials for remote, rapid, and accurate actuation, and offers valuable insights for actuation in harsh and vacuum outdoor environments.

Comparison of proximal and distal laparoscopic ureteroureterostomy for complete duplex kidneys in children.

OBJECTIVE: To compare efficacy of proximal and distal laparoscopic ureteroureterostomy (UU) for complete duplex kidneys in children. METHODS: Patients who underwent laparoscopic UU for complete duplex kidneys between December 2016 and July 2022 were reviewed retrospectively. 71 patients who had normal lower pole moiety without vesicoureteral reflux (VUR) were recruited. All of them underwent ultrasound, voiding cystourethrography (VCUG), renal scintigraphy, and magnetic resonance urography preoperatively. Proximal laparoscopic UU was performed in 35 patients and distal laparoscopic UU in 36 patients. Double J stents were placed in normal lower pole moieties. Clinical data, including general information, diagnosis, surgical management, imaging characteristics, clinical symptoms and postoperative complications (classified according to the modified Clavien-Dindo classification), and length of stay were recorded. Measurement date comparisons between groups were performed by t test, counting date were analyzed by chi-square test. RESULTS: The study consisted of 71 patients (56 females and 15 males) with complete duplex kidneys (41 in left kidney and 30 in right kidney). The patients' mean age was 34 m (range 3-161 m) and follow-up ranged from 25 to 81 m. No significant difference was found in age and follow-up time between the two groups. Laparoscopic UU was performed in all patients successfully. The operation time of the two groups was 108.42 ± 26.95 min for distal UU vs 121.46 ± 35.15 min for proximal UU(p = 0.14). No significant difference in postoperative complications was seen between the two groups (22.2% vs 31.4%, p = 0.345). However, in terms of the grading of postoperative complications, the proximal UU group had a higher grade (3 of them had a grade of IV) and more serious complications. CONCLUSIONS: There was no significant difference in the overall incidence of complications between distal and proximal UU. Compared with proximal laparoscopic UU, distal laparoscopic UU is easier to perform with less injury to the peripheral tissues. Postoperative complications of proximal UU are more serious and more difficult to manage. We recommend complete duplex kidney ureteral reconstruction with distal UU.

Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon-specific CRISPR-Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism-related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.

Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.

INTRODUCTION: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV- and HBV+ HCC have remained unchanged, limiting HCC treatment options. OBJECTIVES: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. METHODS: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. RESULTS: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. CONCLUSION: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids.

The complete degradation of 1,2-dichloroethane in Escherichia coli by metabolic engineering.

1,2-Dichloroethane (1,2-DCA), a widely utilized chemical intermediate and organic solvent in industry, frequently enters the environment due to accidental leaks and mishandling during application processes. Thus, the in-situ remediation of contaminated sites has become increasingly urgent. However, traditional remediation methods are inefficient and costly, while bioremediation presents a green, efficient, and non-secondary polluting alternative. In this study, an engineered strain capable of completely degrading 1,2-DCA was constructed. We introduced six exogenous genes of the 1,2-DCA degradation pathway into E. coli and confirmed their normal transcription and efficient expression in this engineered strain through qRT-PCR and proteomics. The degradation experiments showed that the strain completely degraded 2 mM 1,2-DCA within 12 h. Furthermore, the results of isotope tracing verified that the final degradation product, malic acid, entered the tricarboxylic acid cycle (TCA) of E. coli and was ultimately fully metabolized. Also, morphological changes in the engineered strain and control strain exposed to 1,2-DCA were observed under SEM, and the results revealed that the engineered strain is more tolerant to 1,2-DCA than the control strain. In conclusion, this study paved a new way for humanity to deal with the increasingly complex environmental challenges.

Mechanical properties of municipal solid waste under different stress paths: Effects of plastic content and particle gradation.

Plastics within municipal solid waste (MSW) are non-degradable. As MSW continues to degrade, the relative content of plastics rises, and particle gradation may also change. Moreover, throughout the landfilling process, MSW is subjected to various stress conditions, potentially influencing its mechanical properties. This study explored the effects of varying plastic contents, different particle gradations, and distinct stress paths on the mechanical properties of MSW, and consolidated drained triaxial tests of 42 groups of reconstituted MSW specimens were conducted. The results showed that there was an optimal plastic content of 6-9 % for MSW, where the shear strength of MSW was higher than that of MSW with other plastic contents. When the stress path changed from TC45 to TC72, the optimal plastic content of MSW changed from 6 % to 9 %. As the plastic content increased, both the cohesion and internal friction angle of the MSW initially increased, then subsequently decreased. The impact of plastic content on cohesion was more pronounced than on the internal friction angle, especially at larger strains. Under various stress paths, MSW with distinct particle size distributions demonstrated diverse stress-strain behaviors. Traditional criteria for evaluating well-graded conditions in soils are not suitable for MSW. The effect of gradation on the cohesion of MSW is essentially due to the predominant role of fiber content; the relationship between gradation and the internal friction angle in MSW is complex and correlates closely with the content of both coarse and fine particles, as well as fibers. This study serves as an essential reference for predicting deformations in landfills and analyzing the stability of landfill slopes.

Development and validation of nomograms for predicting prognosis in patients with solitary HCC: A TRIPOD-Compliant study.

Objective: To develop and validate nomograms for predicting the OS and CSS of patients with Solitary Hepatocellular Carcinoma (HCC). Methods: Using the TRIPOD guidelines, this study identified 5206 patients in the Surveillance, Epidemiology, and End Results (SEER) 17 registry database. All patients were randomly divided in a ratio of 7:3 into a training cohort (n = 3646) and a validation cohort (n = 1560), and the Chinese independent cohort (n = 307) constituted the external validation group. The prognosis-related risk factors were selected using univariate Cox regression analysis, and the independent prognostic factors of OS and CSS were identified using the Lasso-Cox regression model. The nomograms for predicting the OS and CSS of the patients were constructed based on the identified prognostic factors. Their prediction ability was evaluated using the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve in both the training and validation cohorts. Results: We identified factors that predict OS and CSS and constructed two nomograms based on the data. The ROC analysis, C-index analysis, and calibration analysis indicated that the two nomograms performed well over the 1, 3, and 5-year OS and CSS periods in both the training and validation cohorts. Additionally, these results were confirmed in the external validation group. Decision curve analysis (DCA) demonstrated that the two nomograms were clinically valuable and superior to the TNM stage system. Conclusion: We established and validated nomograms to predict 1,3, and 5-year OS and CSS in solitary HCC patients, and our results may also be helpful for clinical decision-making.

Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response.

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

Disease-induced changes in bacterial and fungal communities from plant below- and aboveground compartments.

The plant microbes are an integral part of the host and play fundamental roles in plant growth and health. There is evidence indicating that plants have the ability to attract beneficial microorganisms through their roots in order to defend against pathogens. However, the mechanisms of plant microbial community assembly from below- to aboveground compartments under pathogen infection remain unclear. In this study, we investigated the bacterial and fungal communities in bulk soil, rhizosphere soil, root, stem, and leaf of both healthy and infected (Potato virus Y disease, PVY) plants. The results indicated that bacterial and fungal communities showed different recruitment strategies in plant organs. The number and abundance of shared bacterial ASVs between bulk and rhizosphere soils decreased with ascending migration from below- to aboveground compartments, while the number and abundance of fungal ASVs showed no obvious changes. Field type, plant compartments, and PVY infection all affected the diversity and structures of microbial community, with stronger effects observed in the bacterial community than the fungal community. Furthermore, PVY infection, rhizosphere soil pH, and water content (WC) contributed more to the assembly of the bacterial community than the fungal community. The analysis of microbial networks revealed that the bacterial communities were more sensitive to PVY infection than the fungal communities, as evidenced by the lower network stability of the bacterial community, which was characterized by a higher proportion of positive edges. PVY infection further increased the bacterial network stability and decreased the fungal network stability. These findings advance our understanding of how microbes respond to pathogen infections and provide a rationale and theoretical basis for biocontrol technology in promoting sustainable agriculture. KEY POINTS: • Different recruitment strategies between plant bacterial and fungal communities. • Bacterial community was more sensitive to PVY infection than fungal community. • pH and WC drove the microbial community assembly under PVY infection.

Frailty and psychiatric disorders: A bidirectional Mendelian randomization study.

BACKGROUND: The association between frailty and psychiatric disorders has been reported in observational studies. However, it is unclear whether frailty facilitates the appearance of psychiatric disorders or vice versa. Therefore, we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causality. METHODS: Independent genetic variants associated with frailty index (FI) and psychiatric disorders were obtained from large genome-wide association studies (GWAS). The inverse variance weighted method was utilized as the primary method to estimate causal effects, followed by various sensitivity analyses. Multivariable analyses were performed to further adjust for potential confounders. RESULTS: The present MR study revealed that genetically predicted FI was significantly and positively associated with the risk of major depressive disorder (MDD) (odds ratio [OR] 1.79, 95 % confidence interval [CI] 1.48-2.15, P = 1.06 × 10-9), anxiety disorder (OR 1.61, 95 % CI 1.19-2.18, P = 0.002) and neuroticism (OR 1.38, 95 % CI 1.18-1.61, P = 3.73 × 10-5). In the reverse MR test, genetic liability to MDD (beta 0.232, 95 % CI 0.189-0.274, P = 1.00 × 10-26) and neuroticism (beta 0.128, 95 % CI 0.081-0.175, P = 8.61 × 10-8) were significantly associated with higher FI. Multivariable analyses results supported the causal association between FI and MDD and neuroticism. LIMITATIONS: Restriction to European populations, and sample selection bias. CONCLUSIONS: Our study suggested a bidirectional causal association between frailty and MDD neuroticism, and a positive correlation of genetically predicted frailty on the risk of anxiety disorder. Developing a deeper understanding of these associations is essential to effectively manage frailty and optimize mental health in older adults.

Rhizosphere microbial community enrichment processes in healthy and diseased plants: implications of soil properties on biomarkers.

Plant health states may influence the distribution of rhizosphere microorganisms, which regulate plant growth and development. In this study, the response of rhizosphere bacteria and fungi of healthy and diseased plants compared to bulk microbes was analyzed using high-throughput sequencing. Plant adaptation strategies of plants under potato virus Y (PVY) infection have been studied from a microbial perspective. The diversity and community structure of bacteria and fungi varied between bulk and rhizosphere soils, but not between healthy and diseased rhizosphere soils. A LEfSe analysis revealed the significant differences between different treatments on bacterial and fungal community compositions and identified Roseiflexaceae, Sphingomonas, and Sphingobium as the bacterial biomarkers of bulk (BCK), healthy rhizosphere (BHS), and diseased rhizosphere (BIS) soils, respectively; Rhodotorula and Ascomycota_unidentified_1_1 were identified as the fungal biomarkers of bulk (FCK) and healthy rhizosphere (FHS) soils. Bacterial networks were found to be more complex and compact than fungal networks and revealed the roles of biomarkers as network keystone taxa. PVY infection further increased the connectedness among microbial taxa to improve rhizosphere microbial community stability and resistance to environmental stress. Additionally, water content (WC) played an apparent influence on bacterial community structure and diversity, and pH showed significant effects on fungal community diversity. WC and pH greatly affected the biomarkers of bacterial rhizosphere communities, whereas the biomarkers of bulk bacterial communities were significantly affected by soil nutrients, especially for Sphingobium. Overall, the rhizosphere microbial community enrichment processes were different between healthy and diseased plants by changing the community compositions and identifying different biomarkers. These findings provide insight into the assemblage of rhizosphere microbial communities and soil physicochemical properties, which contributes to a deeper understanding of the establishment of an artificial core root microbiota to facilitate plant growth and bolstering resistance mechanisms. This knowledge contributes to a deeper understanding of the establishment of an artificial core root microbiota, thereby facilitating plant growth and bolstering resistance mechanisms.

Rapid development of double-hit mRNA antibody cocktail against orthopoxviruses.

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Interferon-γ in the tumor microenvironment promotes the expression of B7H4 in colorectal cancer cells, thereby inhibiting cytotoxic T cells.

The bioactivity of interferon-γ (IFN-γ) in cancer cells in the tumor microenvironment (TME) is not well understood in the current immunotherapy era. We found that IFN-γ has an immunosuppressive effect on colorectal cancer (CRC) cells. The tumor volume in immunocompetent mice was significantly increased after subcutaneous implantation of murine CRC cells followed by IFN-γ stimulation, and RNA sequencing showed high expression of B7 homologous protein 4 (B7H4) in these tumors. B7H4 promotes CRC cell growth by inhibiting the release of granzyme B (GzmB) from CD8+ T cells and accelerating apoptosis in CD8+ T cells. Furthermore, interferon regulatory factor 1 (IRF1), which binds to the B7H4 promoter, is positively associated with IFN-γ stimulation-induced expression of B7H4. The clinical outcome of patients with CRC was negatively related to the high expression of B7H4 in cancer cells or low expression of CD8 in the microenvironment. Therefore, B7H4 is a biomarker of poor prognosis in CRC patients, and interference with the IFN-γ/IRF1/B7H4 axis might be a novel immunotherapeutic method to restore the cytotoxic killing of CRC cells.

Evaluation of multiscale mechanisms of ultrasound-assisted extraction from porous plant materials: Experiment and modeling on this intensified process.

Ultrasound-assisted extraction (UAE) is an intensified mass transfer process, which can utilize natural resources effectively, but still lacks detailed mechanisms for multiscale effects. This study investigates the mass transfer mechanisms of UAE combined with material's pore structure at multiscale. Porous material was prepared by roasting green coffee beans (GCB) at 120 °C (RCB120) and 180 °C (RCB180), and their UAE efficiency for phytochemicals (caffeine, trigonelline, chlorogenic acid, caffeic acid) were evaluated by experiment and modeling. Besides, the physicochemical properties, mass transfer kinetics, and multi-physical field simulation were studied. Results indicated that positive synergy effects on extraction existed between ultrasound and material's pore structure. Higher mass transfer coefficients of UAE (GCB 0.16 min-1, RCB120 0.38 min-1, RCB180 0.46 min-1) was achieved with higher total porosity (4.47 %, 9.17 %, 13.52 %) and connected porosity (0 %, 3.79 %, 5.98 %). Moreover, simulation results revealed that micro acoustic streaming and pressure difference around particles were the main driving force for enhancing mass transfer, and the velocity (0.29-0.36 m/s) increased with power density (0.64-1.01 W/mL). The microscale model proved that increased yield from UAE-RCB was attributed to internal convection diffusion within particles. This study exploited a novel benefit of ultrasound on extraction and inspired its future application in non-thermal food processing.

Comparative analysis of the clinical features of nonvalvular atrial fibrillation among Tibetan, Han, and Hui patients in Qinghai Province, China.

BACKGROUND: Global nonvalvular AF rises, impacting health severely. In Qinghai, China's diverse setting, studying AF among varied ethnic groups is crucial OBJECTIVES: The purpose of this study was to compares cardiac features in AF among Tibetan, Han, and Hui patients to develop tailored prevention and treatment strategies for this region, the goal was to enhance the understanding of AF and provide an empirical basis for developing prevention and treatment strategies specific to this region METHODS: This study included a total of 3445 Tibetan, Han, and Hui patients diagnosed with nonvalvular atrial fibrillation and treated at the Qinghai Cardiovascular and Cerebrovascular Specialist Hospital, China, between January 2019 and January 2021. We analyzed the differences in cardiac structure, comorbidities, and other influencing factors among the different ethnic groups RESULTS: We found significant differences in gender, age, smoking history, lone atrial fibrillation, left heart failure, dilated cardiomyopathy, and diabetes between Tibetan, Han, and Hui patients (P < 0.05). Tibetan, Han, and Hui patients also differed with regard to left ventricular end-diastolic volume, left ventricular ejection fraction, fractional shortening, NT-proBNP, glycated hemoglobin, red blood cell distribution width, platelet count, platelet hematocrit, platelet distribution width, homocysteine (Hcy), C-reactive protein, and superoxide dismutase (SOD) (P < 0.05) CONCLUSION: Our study revealed variations in comorbidities, cardiac structure, and blood indexes among Tibetan, Han, and Hui AF patients, highlighting distinct patterns in complications and biomarker levels across ethnic groups.