Application of a single-cell-RNA-based biological-inspired graph neural network in diagnosis of primary liver tumors.

Single-cell technology depicts integrated tumor profiles including both tumor cells and tumor microenvironments, which theoretically enables more robust diagnosis than traditional diagnostic standards based on only pathology. However, the inherent challenges of single-cell RNA sequencing (scRNA-seq) data, such as high dimensionality, low signal-to-noise ratio (SNR), sparse and non-Euclidean nature, pose significant obstacles for traditional diagnostic approaches. The diagnostic value of single-cell technology has been largely unexplored despite the potential advantages. Here, we present a graph neural network-based framework tailored for molecular diagnosis of primary liver tumors using scRNA-seq data. Our approach capitalizes on the biological plausibility inherent in the intercellular communication networks within tumor samples. By integrating pathway activation features within cell clusters and modeling unidirectional inter-cellular communication, we achieve robust discrimination between malignant tumors (including hepatocellular carcinoma, HCC, and intrahepatic cholangiocarcinoma, iCCA) and benign tumors (focal nodular hyperplasia, FNH) by scRNA data of all tissue cells and immunocytes only. The efficacy to distinguish iCCA from HCC was further validated on public datasets. Through extending the application of high-throughput scRNA-seq data into diagnosis approaches focusing on integrated tumor microenvironment profiles rather than a few tumor markers, this framework also sheds light on minimal-invasive diagnostic methods based on migrating/circulating immunocytes.

Juvenile hormone signaling is indispensable for late embryogenesis in ametabolous and hemimetabolous insects.

BACKGROUND: Juvenile hormone (JH) is an insect-exclusive hormone involved in regulating diverse aspects of insect physiology, and the evolution of its diverse function is widely interesting. Studying embryogenesis in basal wingless insects is important to understand the functional evolution of JH; however, experimental studies in this regard are scarce. In this study, we conducted CRISPR/Cas9-mediated knockout (KO) of genes involved in JH biosynthesis and signaling cascades in the ametabolous firebrat, Thermobia domestica. Additionally, we investigated whether the primitive action of JH is conserved in the hemimetabolous cricket, Gryllus bimaculatus. RESULTS: We observed that KO of JHAMT, CYP15A1, Met, and Kr-h1 resulted in embryonic lethality in T. domestica. Deprivation of JH or JH signaling arrested the progression of extraembryonic fluid resorption after dorsal closure and hatching, which is consistent with the gene expression pattern showing high Kr-h1 expression in the late embryos of T. domestica. The embryos deficient in JH signaling displayed wrinkled and weak legs. Comparative transcriptome analysis revealed that JH signaling promotes embryonic leg maturation through inducing energy supply and muscle activity, as validated by transmission electron microscopy (TEM). In addition, JH signaling exhibited similar embryonic effects in G. bimaculatus. CONCLUSIONS: This study reveals the indispensable role of JH signaling in facilitating the maturation of terminal tissues during late embryogenesis, as demonstrated by the regulation of leg development, in ametabolous and hemimetabolous insects. These findings further indicate that the embryonic functions of JH evolved earlier than its anti-metamorphic functions during postembryonic development.

[Comparative study of total knee arthroplasty assisted by robot and remote sensing navigation system].

OBJECTIVE: To compare clinical efficacy of robot-assisted (RA) and remote sensing navigation alignment (RSNA) system-assisted total knee arthroplasty (TKA). METHODS: From March 2023 to June 2023, 60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis (KOA) were admitted and divided into RSNA group and RA group according to different treatment methods, with 30 patients in each group. There were 5 males and 25 females in RSNA group, aged from 56 to 81 years old with an average of(66.33±7.16) years old;body mass index(BMI) ranged from 19.87 to 38.54 kg·m-2 with an average of (28.40±6.18) kg·m-2;the courses of disease ranged from 5 to 36 months with an average of (18.20±8.98) months; RSNA system was used to assist the positioning of osteotomy. There were 7 males and 23 females in RA group, aged from 55 to 82 years old with an average of (67.83±8.61) years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an average of (28.01±4.89) kg·m-2; the courses of disease ranged from 3 to 33 months with an average of (17.93±9.20) months;RA was performed. Operation time, incision length, latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups. Hip-knee ankle angle (HKAA), HKAA deviation, lateral distal femoral angle ( LDFA), medial proximal tibial angle (MPTA) and posterior tibial slope (PTS) were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society score (KSS) were used to evaluate functional recovery before operation, 3 and 6 months after operation. RESULTS: The operation was performed successfully in both groups, and there were no serious complications such as vascular and nerve injury during operation. The wound healed well at stageⅠafter operation, and the follow-up time was 6 months. The operation time, latent blood loss at 2 weeks after operation and incision length in RSNA group were (94.35±5.75) min, (130.54±17.53) ml and (14.73±2.14) cm, respectively;while (102.57±6.88) min, (146.33±19.47) ml and (16.78±2.32) cm in RA group, respectively. RSNA group was better than RA group (P<0.05). No deep vein thrombosis occurred in both groups at 2 weeks after operation, 5 patients occurred intermuscular vein thrombosisin in RSNA group and 8 patients in RA group, the difference was not statistically significant (P>0.05). In RSNA group, HKAA, LDFA and MPTA were (173.00±5.54) °, (86.96±3.45) °, (82.79±3.35) ° before operation, and (178.34±1.85) °, (89.92±0.42) °, (89.84±0.73) ° at 1 week after operation, respectively. In RA group, HKAA, LDFA and MPTA were (173.31±6.48) °, (87.15±3.40) ° and (82.99±3.05) ° before operation, and (178.52±1.79) °, (90.03±0.39) ° and (90.15±0.47) ° at 1 week after operation, respectively. HKAA, LDFA and MPTA were significantly improved in both groups at 1 week after operation (P<0.05). There were no significant difference in HKAA, LDFA, MPTA and PTS between two groups before operation and 1 week after operation (P>0.05). There was no significant difference in deviation distribution of HKAA at 1 week after operation (χ2=2.611, P=0.456). There were no significant difference in WOMAC and KSS between two groups before operation, 3 and 6 months after operation (P>0.05), and postoperative WOMAC and KSS at 3 and 6 months between two groups were improved compared with those before operation (P<0.05). CONCLUSION: Both RA and RSNA system assisted TKA could obtain accurate osteotomy, RA has higher surgical accuracy, RSNA system assisted operation has less trauma, and operation is simpler.

[Application of remote sensing navigation system in total knee arthroplasty].

OBJECTIVE: To explore clinical accuracy of remote sensing navigation alignment (RSNA) system in total knee arthroplasty (TKA) and its influence on postoperative clinical efficacy. METHODS: From May 2021 to May 2022, 60 knee osteoarthritis (KOA) patients with Kellgren-Lawrence (K-L) grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods, and 30 patients in each group. There were 6 males and 24 females in RSNA group, aged from 55 to 86 years old with an average of (68.06±8.23) years old;body mass index (BMI) ranged from 22.15 to 34.58 kg·m-2 with an average of (28.20±3.01) kg·m-2;the courses of disease ranged from 2 to 60 months with an average of (18.80±14.80) months;13 patients with grade Ⅲ and 17 patients with grade Ⅳ according to K-L grading. In traditional operation group, there were 8 males and 22 females, aged from 57 to 85 years old with an average of (67.26±6.32) years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of (27.49±2.32) kg·m-2;the courses of disease ranged from 3 to 60 months with an average of (21.30±16.44) months;14 patients with grade Ⅲ and 16 patients with grade Ⅳ according to K-L grading. Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and Knee Society score(KSS) were used to evaluate functional recovery of patients. Hip-knee-ankle angle (HKAA), distal femoral valgus angle (FVA) and distal fermoral flexion angle (DFFA) were measured before operation. HKAA and HKAA deviation angle were measured at 1 week after operation, and defective rate of lower limb force line, femur prosthesis valgus angle (FPVA) and femoral prosthesis flexion angle (FPFA), respectively, were calculated. RESULTS: There were no serious complications such as vascular and nerve injury during operation, and wound healed at stage Ⅰ. Both groups were followed up for 6 months. There were no significant difference in WOMAC index, KSS, HKAA, FVA and DFFA between two groups before operation (P>0.05). The force line defect rate, HKAA, HKAA deviation angle, FPVA deviation angle and FPFA of RSNA group were 6.7%, (178.74±1.56) °, (1.25±1.56) °, (1.84±0.16) ° and (4.85±2.46) °, respectively;while in traditional operation group were 20%, (176.73±3.46) °, (3.27±3.46) °, (2.44±0.26) °, (6.60±1.86) °;the difference between two groups were statistically significant (P<0.05). There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation (P>0.05). CONCLUSION: RSNA system could reduce defective rate of lower limb force line, FPVA deviation angle and FPFA after TKA, which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.

Simultaneous improvement of fiber yield and quality in upland cotton (Gossypium hirsutum L.) by integration of auxin transport and synthesis.

Cotton is a widely planted commercial crop in the world. Enhancing fiber yield and quality is a long-term goal for cotton breeders. Our previous work has demonstrated that fine promotion of auxin biosynthesis in ovule epidermis, by overexpressing FBP7pro::iaaM, has a significant improvement on lint yield and fiber fineness. Lately, transgenic cottons overexpressing GhROP6 variants modify mature fiber length by controlling GhPIN3a-mediated polar auxin transport in ovules. Here, this study showed that all these GhROP6-related cottons displayed unsatisfactory agronomic performance in field conditions. Yet extra auxin supply could promote their fiber development, suggesting inadequate auxin supply in the ovules. Thus, these cottons were integrated with enhanced auxin synthesis by crossing with FBP7pro::iaaM cotton. All the transgene-stacked cottons exhibited synergetic effects on cotton yield (seedcotton yield, lint yield, and lint percentage) and quality (length, strength, and micronaire). Notably, comparing to the FBP7pro::iaaM background, the transgene-stacked cotton co-expressing FBP7pro::iaaM and CA-ghrop6 (constitutively active GhROP6) exhibited a 12.6% increase in seedcotton yield and a 19.0% increase in lint yield over a three-year field trial, and simultaneously resulted in further improvement on fiber length, strength, and micronaire. Collectively, our data provide a potential strategy for genetic improvement on cotton fiber yield and quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01500-w.

Exploring Radiotherapy as a Promising Alternative for Managing Advanced Upper Tract Urothelial Carcinoma: Rescuing Chemotherapy-Intolerant Patients.

PURPOSE: To investigate the safety and effectiveness of radiotherapy for advanced upper tract urothelial carcinoma (UTUC) patients intolerant to chemotherapy. METHODS: Data for 21 patients with advanced UTUC intolerant to chemotherapy were retrospectively collected. All patients were treated with conventionally fractionated radiotherapy (50-70 Gy/20-33 f) or partial-SABR boost to the lesions (50-60 Gy/20-25 f with tumor center boosted with 6-8 Gy/f, 3-5 f) for bulky tumors. RESULTS: The median age was 75 years (range, 58-87 years). Primary tumor resection was performed for all patients and none underwent metastatic resection. Seventeen (81%) patients had oligometastasis (1-5 metastases) at diagnosis. Eighteen (85.7%) received irradiation to all tumor lesions. Lymph node metastasis was predominant in the whole group (17/21). Other lesions were distributed as local recurrence (7/21), bone metastases (2/21) and abdominal wall/muscle (2/21). The median follow-up time was 38.5 months (interquartile range, 15.2-48.7 months). Rate of local control (LC), progression-free survival (PFS) and overall survival (OS) of the whole group at 1 year were 90%, 46.6%, and 80.4%, respectively. At 3 years, LC, PFS and OS were 65.6%, 26.6%, and 40.9%, respectively. Fourteen patients developed acute mild gastrointestinal toxicity, generally of grade 1-2; 8 patients developed acute grade 1-2 hematological toxicity, consisting mainly of anemia and leukopenia. No grade 3 or higher acute or late toxicities were observed. CONCLUSION: For patients with advanced UTUC who are not able to tolerate chemotherapy, radiotherapy is a safe treatment and can achieve good local tumor control.

MvGraphDTA: multi-view-based graph deep model for drug-target affinity prediction by introducing the graphs and line graphs.

BACKGROUND: Accurately identifying drug-target affinity (DTA) plays a pivotal role in drug screening, design, and repurposing in pharmaceutical industry. It not only reduces the time, labor, and economic costs associated with biological experiments but also expedites drug development process. However, achieving the desired level of computational accuracy for DTA identification methods remains a significant challenge. RESULTS: We proposed a novel multi-view-based graph deep model known as MvGraphDTA for DTA prediction. MvGraphDTA employed a graph convolutional network (GCN) to extract the structural features from original graphs of drugs and targets, respectively. It went a step further by constructing line graphs with edges as vertices based on original graphs of drugs and targets. GCN was also used to extract the relationship features within their line graphs. To enhance the complementarity between the extracted features from original graphs and line graphs, MvGraphDTA fused the extracted multi-view features of drugs and targets, respectively. Finally, these fused features were concatenated and passed through a fully connected (FC) network to predict DTA. CONCLUSIONS: During the experiments, we performed data augmentation on all the training sets used. Experimental results showed that MvGraphDTA outperformed the competitive state-of-the-art methods on benchmark datasets for DTA prediction. Additionally, we evaluated the universality and generalization performance of MvGraphDTA on additional datasets. Experimental outcomes revealed that MvGraphDTA exhibited good universality and generalization capability, making it a reliable tool for drug-target interaction prediction.

[An in vitro experiment on the stability and irritant of hypochlorous acid in oral cavity].

PURPOSE: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity. METHODS: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data. RESULTS: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P＞0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P＜0.001). CONCLUSIONS: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.

A new dicyanophenanthrene-based thermally activated delayed fluorophore: Design, synthesis, photophysical study, and electroluminescence application.

A novel thermally activated delayed fluorescence (TADF) emitter, DCNP-SCF, is developed based on a dicyanophenanthrene acceptor. DCNP-SCF is prepared by a simple C-N coupling reaction. Its thermal, theoretical, photophysical, and electroluminescent properties are investigated, emphasizing its potential in organic electroluminescence devices. DCNP-SCF demonstrates highly distorted donor-acceptor conformation, facilitating significant TADF for efficient triplet harvesting in electroluminescence devices. Additionally, due to the moderate electron push-pull effect, DCNP-SCF exhibits appropriate intramolecular charge transfer for considerable photoluminescence quantum yield for electroluminescence applications.

Numerical investigation on the impact of different coronary aneurysms morphologies on thrombus formation and hemodynamics: a comparative study.

Coronary artery aneurysms (CAAs) are morphologically classified as saccular and fusiform. There is still a great deal of clinical controversy as to which types of CAA are more likely to cause thrombosis. Therefore, the main objective of this study was to evaluate the trend of thrombus growth in CAAs with different morphologies and to assess the risk of possible long-term complications based on hemodynamic parameters. Utilizing computed tomography angiography (CTA) data from eight healthy coronary arteries, two distinct morphologies of coronary artery aneurysms (CAAs) were reconstructed. Distribution of four wall shear stress (WSS)-based indicators and three helicity indicators was analyzed in this study. Meanwhile, a thrombus growth model was introduced to analyze the thrombus formation in CAAs with different morphologies. The research results showed the distribution of most WSS indicators between saccular and fusiform CAAs was not statistically significant. However, due to the presence of a more pronounced helical flow pattern, irregular helical flow structure and longer time of flow stagnation in saccular CAAs during the cardiac cycle, the mean and maximum relative residence time (RRT) were significantly higher in saccular CAAs than in fusiform CAAs (P < 0.05). This may increase the risk of saccular coronary arteries leading to aneurysmal dilatation or even rupture. Although the two CAAs had similar rates of thrombosis, fusiform CAAs may more early cause obstruction of the main coronary flow channel where the aneurysm is located due to thrombosis growth. Thus, the risk of thrombosis in fusiform coronary aneurysms may warrant greater clinical concern.

CoF-DResNet: Cancer Metastasis Recognition Network based on Dynamic Coordinated Metabolic Attention and Structural Attention.

BACKGROUND: Cancer metastasis usually means that cancer cells spread to other tissues or organs, and the condition worsens. Identifying whether cancer has metastasized can help doctors infer the progression of a patient's condition and is an essential prerequisite for devising treatment plans. Fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18F -FDG PET/CT) is an advanced cancer diagnostic imaging technique that provides both metabolic and structural information. METHOD: In cancer metastasis recognition tasks, effectively integrating metabolic and structural information stands as a key technology to enhance feature representation and recognition performance. This paper proposes a cancer metastasis identification network based on dynamic coordinated metabolic attention and structural attention to address these challenges. Specifically, metabolic and structural features are extracted by incorporating a dynamic coordinated attention module (DCAM) into two branches of ResNet networks, thereby amalgamating high metabolic spatial information from PET images with texture structure information from CT images, and dynamically adjusting this process through iterations. DISCUSSION: Next, to improve the efficacy of feature expression, a multi-receptive field feature fusion module (MRFM) is included in order to execute multi-receptive field fusion of semantic features. RESULT: To validate the effectiveness of our proposed model, experiments were conducted on both a private lung lymph nodes dataset and a public soft tissue sarcomas dataset. CONCLUSION: The accuracy of our method reached 76.0% and 75.1% for the two datasets, respectively, demonstrating an improvement of 6.8% and 5.6% compared to ResNet, thus affirming the efficacy of our method.

Inflammatory shift alterations of proinflammatory and anti-inflammatory cytokines in unexplained recurrent miscarriage patients.

This study aimed to investigate the pro-inflammatory and anti-inflammatory cytokines status in the peripheral blood of uRM patients. The plasma pro-inflammatory (IFN-γ, IL-6, IL-1ß, and TNF-α) and anti-inflammatory (TGF-ß1, IL-10, and IL-4) cytokines of 25 patients with uRM were compared to 33 women with a successful pregnancy. It was concluded that patients with uRM have an excess pro-inflammatory cytokines status.

BpAFP, a Broussonetia papyrifera latex chitinase, exhibits a dual role in resisting to both Verticillium wilt disease and lepidopterous pests, Plutella xylostella and Prodenia litura.

Paper mulberry (Broussonetia papyrifera) is a fast-growing tree known for its tolerance to diverse biotic and abiotic stresses. To explore genes combating Verticillium wilt, a devasting and formidable disease damage to cotton and many economically significant crops, we purified an antifungal protein, named BpAFP, from the latex of paper mulberry. Based on peptide fingerprint, we cloned the full cDNA sequence of BpAFP and revealed that BpAFP belongs to Class I chitinases, sharing 74 % identity with B. papyrifera leaf chitinase, PMAPII. We further introduced BpAFP into Arabidopsis, tobacco, and cotton. Transgenic plants exhibited significant resistance to Verticillium wilt. Importantly, BpAFP also demonstrated insecticidal activity against herbivorous pests, Plutella xylostella, and Prodenia litura, when feeding the larvae with transgenic leaves. Our finding unveils a dual role of BpAFP in conferring resistance to both plant diseases and lepidopterous pests.

Associations of Urinary Heavy Metal Mixtures with High Remnant Cholesterol among US Adults: Evidence from the National Health and Nutrition Examination Survey (1998-2018).

The main objective of our study is to explore the associations between combined exposure to urinary heavy metals and high remnant cholesterol (HRC), a known cardiovascular risk factor. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018, we conducted a cross-sectional analysis of 5690 participants, assessing urinary concentrations of ten heavy metals. Ten heavy metals in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Fasting residual cholesterol ≥0.8 mmol/L was defined as HRC (using blood samples). Statistical analyses included weighted multivariable logistic regression, weighted quantile sum (WQS) regression, quantile g-computation (qgcomp), and Bayesian kernel machine regression (BKMR) to evaluate the associations of heavy metal exposure with HRC. Stratified analyses based on individual characteristics were also conducted. Multivariable logistic regression found that the four metals (OR Q4 vs. Q1: 1.33, 95% CI: 1.01-1.75 for barium (Ba); OR Q4 vs. Q1: 1.50, 95% CI: 1.16-1.94 for cadmium (Cd); OR Q4 vs. Q1: 1.52, 95% CI: 1.15-2.01 for mercury (Hg); OR Q4 vs. Q1: 1.35, 95% CI: 1.06-1.73 for lead (Pb)) were positively correlated with the elevated risk of HRC after adjusting for covariates. In addition, all three mixed models, including WQS (OR: 1.25; 95% CI: 1.07-1.46), qgcomp (OR: 1.17; 95% CI: 1.03-1.34), and BKMR, consistently showed a significant positive correlation between co-exposure to heavy metal mixtures and HRC, with Ba and Cd being the main contributors within the mixture. These associations were more pronounced in younger adults (20 to 59 years), males, and those with a higher body mass index status (≥25 kg/m2). Our findings reveal a significant relationship between exposure to the mixture of heavy metals and HRC among US adults, with Ba and Cd being the major contributors to the mixture's overall effect. Public health efforts aimed at reducing heavy metal exposure can help prevent HRC and, in turn, cardiovascular disease.

[Study on mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site on CCl_4-induced chronic liver injury in rats].

This study aims to investigate the mitigating effect and mechanism of Cichorium glandulosum n-butanol extraction site(CGE) on the disease in carbon tetrachloride(CCl_4)-induced chronic liver injury model in rats. A chronic liver injury model was constructed by subcutaneous injection of CCl_4 olive oil solution, and after four weeks of CGE treatment, serum levels of aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(AKP), hydroxyproline(HYP), interleukin-4(IL-4), interleukin-6(IL-6), malondialdehyde(MDA), superoxide dismutase(SOD), and tumor necrosis factor-α(TNF-α) were detected. Liver tissue was processed by hematoxylin-eosin(HE) staining and Masson staining to observe the structure of the rat liver. qPCR and Western blot were used to examine the expression of transforming growth factor-ß1(TGF-ß1)/small mothers against decapentaplegic(Smad), Toll-like receptor 4(TLR4), α-smooth muscle actin(α-SMA), and fibronectin(Fn) in rat liver tissue and hepatic stellate-T6(HSC-T6) and evaluate the inhibitory effect of CGE on HSC activation. The results showed that CGE could significantly reduce the serum levels of AST, ALT, AKP, HYP, and affect the levels of related inflammatory indexes including IL-4, IL-6, and TNF-α, and MDA in CCl_4-induced chronic liver injury in rats and had no effect on SOD activity, which could delay the process of liver injury, alleviate the hepatic collagen deposition and inflammatory infiltration, and had significant efficacy in mitigating chronic liver injury in rats. CGE could inhibit α-SMA and TLR4 protein expression in the liver tissue and reverse the increased TGF-ß1/Smad, Fn, and TLR4-related expression in HSC-T6 in vitro. The above results indicated that CGE exerted hepatoprotective effects in rats by inhibiting HSC activation and alleviated CCl_4-induced chronic liver injury in rats and could ameliorate inflammatory response and slight liver fibrosis in rat liver tissue. Its pharmacodynamic mechanism might be related to TGF-ß1/Smad and TLR4-related expression.

GhMYB52 Like: A Key Factor That Enhances Lint Yield by Negatively Regulating the Lignin Biosynthesis Pathway in Fibers of Upland Cotton (Gossypium hirsutum L.).

In the context of sustainable agriculture and biomaterial development, understanding and enhancing plant secondary cell wall formation are crucial for improving crop fiber quality and biomass conversion efficiency. This is especially critical for economically important crops like upland cotton (Gossypium hirsutum L.), for which fiber quality and its processing properties are essential. Through comprehensive genome-wide screening and analysis of expression patterns, we identified a particularly high expression of an R2R3 MYB transcription factor, GhMYB52 Like, in the development of the secondary cell wall in cotton fiber cells. Utilizing gene-editing technology to generate a loss-of-function mutant to clarify the role of GhMYB52 Like, we revealed that GhMYB52 Like does not directly contribute to cellulose synthesis in cotton fibers but instead represses a subset of lignin biosynthesis genes, establishing it as a lignin biosynthesis inhibitor. Concurrently, a substantial decrease in the lint index, a critical measure of cotton yield, was noted in parallel with an elevation in lignin levels. This study not only deepens our understanding of the molecular mechanisms underlying cotton fiber development but also offers new perspectives for the molecular improvement of other economically important crops and the enhancement of biomass energy utilization.

Unraveling the genetic basis of the causal association between inflammatory cytokines and osteonecrosis.

Background: Previous studies have reported that the occurrence and development of osteonecrosis is closely associated with immune-inflammatory responses. Mendelian randomization was performed to further assess the causal correlation between 41 inflammatory cytokines and osteonecrosis. Methods: Two-sample Mendelian randomization utilized genetic variants for osteonecrosis from a large genome-wide association study (GWAS) with 606 cases and 209,575 controls of European ancestry. Another analysis included drug-induced osteonecrosis with 101 cases and 218,691 controls of European ancestry. Inflammatory cytokines were sourced from a GWAS abstract involving 8,293 healthy participants. The causal relationship between exposure and outcome was primarily explored using an inverse variance weighting approach. Multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were concurrently applied to bolster the final results. Results: The results showed that bFGF, IL-2 and IL2-RA were clinically causally associated with the risk of osteonecrosis (OR=1.942, 95% CI=1.13-3.35, p=0.017; OR=0.688, 95% CI=0.50-0.94, p=0.021; OR=1.386, 95% CI=1.04-1.85, p = 0.026). there was a causal relationship between SCF and drug-related osteonecrosis (OR=3.356, 95% CI=1.09-10.30, p=0.034). Conclusion: This pioneering Mendelian randomization study is the first to explore the causal link between osteonecrosis and 41 inflammatory cytokines. It conclusively establishes a causal association between osteonecrosis and bFGF, IL-2, and IL-2RA. These findings offer valuable insights into osteonecrosis pathogenesis, paving the way for effective clinical management. The study suggests bFGF, IL-2, and IL-2RA as potential therapeutic targets for osteonecrosis treatment.

Litoamentenes A-K, eleven undescribed cembranoids with cytotoxicity from the South China Sea soft coral Litophyton amentaceum.

Eleven undescribed cembrane-type diterpenoids, named litoamentenes A-K (1-11), were isolated from the soft coral Litophyton amentaceum collected from the South China Sea. Their structures were elucidated by extensive analysis of spectroscopic data, comparison with the literature data, single crystal X-ray diffraction, quantum chemical calculations and TDDFT-ECD calculations. This is the first systematic investigation of L. amentaceum. In particular, compounds 1-3 are cembrane-type norditerpenoids that lack isopropyl side chains. Compound 6 is a cembrane-type norditerpenoid without a methyl group at C-4, the first natural product identified with this carbon skeleton. Compounds 6, 9 and 10 showed modest cytotoxicity against several human cancer cell lines with IC50 values ranging from 3.99 to 14.56 µM.

Effects of Ultrasonic Treatment on Physical Stability of Lily Juice: Rheological Behavior, Particle Size, and Microstructure.

The aim of this study was to investigate the rheological properties, particle size distribution, color change, and stability of lily juice under different ultrasonic treatment conditions (152 W, 304 W, 456 W, 608 W, and 760 W). The results showed that the lily juice exhibited non-Newtonian shear thinning behavior, and the viscosity decreased with the increase in ultrasonic power. Under ultrasonic treatment conditions, there was no significant change in the pH value and zeta potential value of the samples. The content of cloudy value and total soluble solids (TSS) increased gradually. However, both the sedimentation components and centrifugal sedimentation rate showed a downward trend and an asymptotic behavior. In addition, high-power ultrasound changed the color index (L* value decreased, a* value increased), tissue structure, and particle distribution of the sample, and small particles increased significantly. To sum up, ultrasonic treatment has great potential in improving the physical properties and suspension stability of lily juice.

Assessing the impact of tear direction in coronary artery dissection on thrombosis development: A hemodynamic computational study.

OBJECTIVE: Iatrogenic coronary artery dissection is a complication of coronary intimal injury and dissection due to improper catheter manipulation. The impact of tear direction on the prognosis of coronary artery dissection (CAD) remains unclear. This study examines the hemodynamic effects of different tear directions (transverse and longitudinal) of CAD and evaluates the risk of thrombosis, rupture and further dilatation of CAD. METHODS: Two types of CAD models (Type I: transverse tear, Type II: longitudinal tear) were reconstructed from the aorto-coronary CTA dataset of 8 healthy cases. Four WSS-based indicators were analyzed, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and cross flow index (CFI). A thrombus growth model was also introduced to predict the trend of thrombus growth in CAD with two different tear directions. RESULTS: For most of the WSS-based indicators, including TAWSS, RRT, and CFI, no statistically significant differences were observed across the CAD models with varying tear directions, except for OSI, where a significant difference was noted (p < 0.05). Meanwhile, in terms of thrombus growth, the thrombus growing at the tear of the Type I (transverse tear) CAD model extended into the true lumen earlier than that of the Type II (longitudinal tear) model. CONCLUSIONS: Numerical simulations suggest that: (1) The CAD with transverse tear have a high risk of further tearing of the dissection at the distal end of the tear. (2) The CAD with longitudinal tear create a hemodynamic environment characterized by low TAWSS and high OSI in the false lumen, which may additionally increase the risk of vessel wall injury. (3) The CAD with transverse tear may have a higher risk of thrombosis and coronary obstruction and myocardial ischemia in the early phase of the dissection.