Relationship between the interfacial properties of lactoferrin-(-)-epigallocatechin-3-gallate covalent complex and the macroscopic properties of emulsions.

This study explored the relationship between the interfacial behavior of lactoferrin-(-)-epigallocatechin-3-gallate covalent complex (LF-EGCG) and the stability of high internal phase Pickering emulsions (HIPPEs). The formation of covalent bond between lactoferrin and polyphenol was verified by the increase in molecular weight. In LF-EGCG group, the surface hydrophobicity, interfacial pressure, and adsorption rate were decreased, while the molecular flexibility, interfacial film viscoelasticity, and interfacial protein content were increased. Meanwhile, LF-EGCG HIPPE possessed reduced droplet size, increased ζ-potential and stability. Rheology showed the viscoelasticity, structural recovery and gel strength of LF-EGCG HIPPE were improved, giving HIPPE inks better 3D printing integrity and clarity. Moreover, the free fatty acids (FFA) release of LF-EGCG HIPPE (62.6%) was higher than that of the oil group (50.1%). Therefore, covalent treatment effectively improved the interfacial properties of protein particles and the stability of HIPPEs. The macroscopic properties of HIPPEs were positively regulated by the interfacial properties of protein particles. The result suggested that the stability of emulsions can be improved by regulating the interfacial properties of particles.

Locoregional interventional therapy for hepatocellular carcinoma: radiologic and clinical factors predictive of untreatable progression and time to untreatable progression.

Objective: In this retrospective cohort study, independent risk factors that influence untreatable progression (UP) and time to UP (TTUP) in patients with hepatocellular carcinoma (HCC) after locoregional interventional therapy were examined. The effects of initial response and best response on UP occurrence and TTUP after locoregional interventional therapy were evaluated. Methods: Data were collected from HCC patients who were initially treated with the drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) procedure at our hospital from January 2017 to December 2022. Modified response evaluation criteria in solid tumors (m-RECIST) was used to evaluate the radiologic response of tumors. Logistic regression analysis was used to analyze the risk factors for UP in patients, and Cox regression analysis was used to discover independent variables that influenced TTUP. Results: A total of 93 patients who initially underwent the DEB-TACE procedure were included. Subsequent to initial treatment, 50 patients continued with DEB-TACE treatment, while 43 received DEB-TACE and sequential thermal ablation treatment. The probability of developing UP was 82.8% (n = 77). Furthermore, 49 (52.7%) patients achieved an initial response, and 70 (75.3%) achieved the best response. Multivariate logistic regression analysis confirmed three independent risk factors of UP, namely, age (odds ratio [OR]: 0.950, p = 0.044); initial response (OR: 0.177, p = 0.020); and treatment regimen (OR: 7.133, p = 0.007). Multivariate Cox regression found that total bilirubin (hazard ratio [HR]: 1.029, p = 0.002), tumor distribution (HR: 1.752, p = 0.034), Subjective Angiographic Chemoembolization Endpoint (SACE) classification (HR: 0.668, p = 0.043), number of tumors (HR: 1.130, p = 0.004), initial response (HR: 0.539, p = 0.019), and treatment regimen (HR: 4.615, p < 0.001) were independent variables that influenced TTUP. Conclusions: Age, initial response, and treatment regimen significantly affected the occurrence of UP in HCC patients. Initial response, SACE classification, treatment regimen, total bilirubin, number of tumors, and tumor distribution were significantly correlated with TTUP. The initial response following locoregional interventional therapy had greater effects on UP occurrence and TTUP than the best response.

A Novel, Dual-Initiator, Continuous-Suspension Grafting Strategy for the Preparation of PP-g-AA-MAH Fibers to Remove of Indigo from Wastewater.

The indigo dye found in wastewater from printing and dyeing processes is potentially carcinogenic, teratogenic, and mutagenic, making it a serious threat to the health of animals, plants, and humans. Motivated by the growing need to remove indigo from wastewater, this study prepared novel fiber absorbents using melt-blow polypropylene (PP) melt as a matrix, as well as acrylic acid (AA) and maleic anhydride (MAH) as functional monomers. The modification conditions were studied to optimize the double-initiation, continuous-suspension grafting process, and then functional fibers were prepared by melt-blown spinning the modified PP. The results showed that the optimum modification conditions were as follows: a 3.5 wt% interfacial agent, 8 mg/L of dispersant, 80% monomer content, a 0.8 mass ratio of AA to MAH, a 1000 r/min stir speed, 3.5 wt% initiator DBPH grafting at 130 °C for 3 h, and 1 wt% initiator BPO grafting at 90 °C for 2 h. The highest grafting rate of the PP-g-AA-MAH was 31.2%, and the infrared spectrum and nuclear magnetic resonance spectroscopic analysis showed that AA and MAH were successfully grafted onto PP fiber. This modification strategy also made the fibers more hydrophilic. The adsorption capacity of the PP-g-AA-MAH fibers was highly dependent on pH, and the highest indigo adsorption capacity was 110.43 mg/g at pH 7. The fiber adsorption capacity for indigo increased rapidly before plateauing with increasing time or indigo concentration, and the experimental data were well described in a pseudo-second-order kinetic model and a Langmuir isothermal adsorption model. Most impressively, the modified fiber adsorption capacity for indigo remained as high as 91.22 mg/g after eight regeneration and reuse cycles. In summary, the PP-g-AA-MAH fibers, with excellent adsorption-desorption characteristics, could be readily regenerated and reused, and they are a promising material for the removal of indigo from wastewater.

Human milk fat substitutes rich in 1,3-dioleoyl-2-palmitoylglycerol and 1-oleoyl-2-palmitoyl-3-linoleoylglycerol simultaneously: Preparation strategy and simulated infant in vitro digestion.

In this study, fractionated palm stearin, oleic acid, and linoleic acid were selected as the base materials to prepare human milk fat substitutes (HMFS) rich in OPO and OPL by enzymatic acidolysis combined with physical blending. Under optimum conditions, contents of OPO, OPL, and sn-2 palmitic acid in the OPO and OPL-rich triacylglycerols (TAGs) were higher than that in commercial OPO-rich TAGs, with values of 37.25%, 28.12%, and 79.44%, respectively. Physical blending the OPO and OPL-rich TAGs (47%), bovine milk fat (18%), sunflower oil (13%), coconut oil (13%), corn oil (8%), and palm oil (1%) can obtain HMFS with a fat composition that like HMF. The fatty acid, sn-2 saturated fatty acid, and TAG contents of HMFS were within the lower and upper limit of HMF. The lipolysis degree of infant formula (IF) with HMFS as fat source is 9.0% higher than that of commercial plant oil-based infant formula (PIF), and 3.4% lower than that of human milk. IF with HMFS as fat source released less saturated free fatty acids and more saturated monoacylglycerols during digestion than that of PIF, which would help improve the IF fat utilization by infants.

High-Emissivity Double-Layer ZrB2-Modified Coating on Flexible Aluminum Silicate Fiber Fabric with Enhanced Oxidation Resistance and Tensile Strength.

Fibers crystallize and become brittle at high temperatures for a long time, so the surface coating must maintain long-lasting emission performance, which requires superior antioxidant properties of the high-emissivity fillers. To improve the radiation performance of the coating and the tensile strength of the fiber fabric, a double-layer coating with high emissivity was prepared on the surface of flexible aluminum silicate fiber fabric (ASFF) using MoSi2 and SiC as emissive agents. The incorporation of borosilicate glass into the outer coating during high-temperature oxidation of ZrB2 results in superior encapsulation of emitter particles, effectively filling the pores of the coating and significantly reducing the oxidation rate of MoSi2 and SiC. Furthermore, the addition of an intermediate ZrO2 layer enhances the fiber bundle's toughness. The obtained double-coated ASFF exhibits an exceptionally high tensile strength of 57.6 MPa and a high bond strength of 156.2 kPa. After being subjected to a 3 h heating process, the emissivity exhibits a minimal decrease of only 0.032, while still maintaining a high value above 0.9. The thermal insulation composites, consisting of a flexible ASFF matrix and a ZrB2-modified double-layer coating, exhibit significant potential for broad applications in the field of thermal protection.

Effect of non-covalent binding of tannins to sodium caseinate on the stability of high-internal-phase fish oil emulsions.

In this study, we designed the noncovalent binding of sodium caseinate (SC) to tannic acid (TA) to stabilize high internal phase emulsions (HIPEs) used as fish oil delivery systems. Hydrogen bonding was the dominant binding force, followed by weak hydrophobic interaction and weak van der Waals forces, as demonstrated by FTIR, fluorescence spectroscopy, and molecular docking experiments, with a binding constant of 3.25 × 106, a binding site of 1.2, and a static quenching of the binding. Increasing SC:TA from SC to 2:1 decreased the particle size from 107.37 ± 10.66 to 76.07 ± 2.77 nm and the zeta potential from -6.99 ± 2.71 to -22 ± 2.42 mV. TA increased the interfacial tension of SC, decreased the surface hydrophobicity from 1.3 × 104 to 1.6 × 103 and improved the oxidation resistance of SC. The particle size of high internal phase emulsions stabilized by complexes with different mass ratios (SC:TA from 1:0 to 2:1) increased from 4.9 ± 0.02 to 12.9 µm, the potential increased from -32.37 ± 2.7 to -35.07 ± 2.58 mV, and the instability index decreased from 0.75 to 0.02. Thicker interfacial layers could be observed by laser confocal microscopy, and an increase in the storage modulus indicated a formation of a stronger gel network. SC:TA of 1:0 showed emulsion breakage after 14 d of storage at room temperature. SC:TA of 2:1 showed the lowest degree of oil-water separation after freeze-thaw treatment. Especially, the most stable high endo-phase emulsion (at SC:TA of 2:1) prepared at each mass ratio was selected for further stability exploration. The emulsion particle size increased only from 15.63 ± 0.06 to 22.27 ± 0.35 µm at salt ion concentrations of 50-200 mM and to 249.33 ± 31.79 µm at 300 mM. The instability index and storage modulus of the high endo-phase emulsions increased gradually with increasing salt ion concentrations. At different heating temperatures (55-85 °C), the instability index of the high internal phase emulsion gradually decreased and the storage modulus gradually increased. Meanwhile, at 50 °C for 15 d of accelerated oxidation, the content of hydroperoxide decreased from 53.32 ± 0.18 to 37.48 ± 0.77 nmol/g, about 29.7 %, and the thiobarbituric acid value decreased from 1.06 × 103 to 0.8 × 103, about 24.5 %, in the high endo-phase emulsions prepared by 2:1 SC:TA compared to the fish oils, and the SC-stabilized high endo-phase only emulsion broke at the sixth day of oxidation. From the above findings, it was concluded that the high internal phase emulsion prepared with SC:TA of 2:1 can be used as a good delivery system for fish oil.

The trajectories of psychosocial adjustment among young to middle-aged women with breast cancer: A prospective longitudinal study.

PURPOSE: This study aims to explore heterogeneous trajectories of psychosocial adjustment among young to middle-aged women with breast cancer and determine the predictive factors influencing these trajectories. METHODS: This study was conducted from October 2019 to October 2022 across two hospitals in Guangzhou. Demographic and disease characteristics, psychosocial adjustment, self-efficacy, social support, and coping modes were collected at baseline. Follow-up evaluations of psychosocial adjustment occurred at 1, 3, and 6 months post-surgery. Latent class growth modeling identified distinct patterns of psychosocial adjustment trajectories. Logistic regression analysis determined the predictive factors. RESULTS: A total of 377 young to middle-aged women with breast cancer participated in this study, with 289 participants completing the 6-month follow-up. Three distinct trajectories of psychosocial adjustment were identified including a "sustained severe maladjustment" trajectory, comprising 22.5% of participants, a "sustained moderate maladjustment" trajectory, comprising 50.4% of participants, and a "well-adjusted class" trajectory, comprising 27.1% of participants. Predictors of psychosocial adjustment trajectories included affected side, surgical type, chemotherapy, self-efficacy, social support, and coping modes. CONCLUSIONS: This study revealed three distinct trajectories of psychosocial adjustment among young to middle-aged women with breast cancer. Those with right-sided breast cancer, undergoing total mastectomy, receiving chemotherapy, low self-efficacy, limited social support, and relying on confrontation or avoidance coping modes may experience sustained maladjustment.

Transcriptomic Analysis Reveals the Flavonoid Biosynthesis Pathway Involved in Rhizome Development in Polygonatum cyrtonema Hua.

Polygonatum cyrtonema Hua (P. cyrtonema) rhizomes are rich in flavonoids and other secondary metabolites, exhibiting remarkable antioxidant, anti-tumor, and immunomodulatory effects. Polygonatum flavonoid-biosynthesis-related genes have been characterized already. However, a comprehensive overview of Polygonatum flavonoid biosynthesis pathways is still absent. To articulate the accumulation of the flavonoid biosynthesis pathways, we examined transcriptome changes using Illumina HiSeq from five different tissues and the RNA-seq of 15 samples had over 105 Gb of a clean base, generating a total of 277,955 unigenes. The cDNA libraries of the fruits (F), leaves (L), roots (R), stems (S), and rhizomes (T) of three-year-old P. cyrtonema plants generated 57,591, 53,578, 60,321, 51,530, and 54,935 unigenes. Comparative transcriptome analysis revealed that 379 differentially expressed genes (DEGs) were in the group of F _vs_ T, L _vs_ T, R _vs_ T, and S _vs_ T, and the transcripts of flavonoid-biosynthesis-related DEGs were principally enriched in rhizomes. In addition, combined with WGCNA and the FPKM of five tissues' transcription, nine differentially expressed transcription factor families (MYB, WRKY, AP2/ERF, etc.) were characterized in the red module, the red module positively correlated with rhizome flavonoid accumulation. Quantitative real-time PCR (qRT-PCR) further indicated that BZIP1, C3H31, ERF114, and DREB21 are differentially expressed in rhizomes, accompanied in rhizome development in P. cyrtonema. Therefore, this study provides a foundation for further research into uncovering the accumulation of flavonoid biosynthesis in the rhizomes of P. cyrtonema.

Establishment of a Posttraumatic Osteoarthritis Model in Mice Induced by Noninvasive Anterior Cruciate Ligament Tear.

BACKGROUND: Animal models that use open surgical transection of the anterior cruciate ligament (ACL) do not accurately simulate the clinical condition regarding the pivot-shift mechanism and the associated inflammatory response that occurs before reconstruction. PURPOSE/HYPOTHESIS: The purpose was to characterize a reproducible manual, nonsurgical method to mimic an isolated ACL tear in a clinically relevant model and to evaluate the development of progressive posttraumatic osteoarthritis due to ACL injury. It was hypothesized that the ACL could be reproducibly torn with minimal damage to other ligaments and that there would be progressive development of degenerative joint disease after ACL injury. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 37 mice (strain C57BL/6) were used to compare the manual procedure with sham surgery (sham group; n = 10) and with the established surgical ACL transection (ACLT) procedure (surgical group; n = 27). In the sham group, a closed manual procedure was performed on the right knee and sham surgery on the left knee. In the surgical group, the closed manual procedure was performed on the right knee and surgical ACLT on the left knee. Dissection using India ink, histological assessment with safranin O and hematoxylin-eosin staining, radiological evaluation through radiographs and microfocus computed tomography scans, and gait analyses were performed to assess cartilage/ligament status. Osteoarthritis Research Society International (OARSI) and synovitis scores, anterior tibial translation, range of motion, bone microstructure, osteophyte volume, and pain were assessed at 2, 4, and 8 weeks postoperatively. RESULTS: The manual procedure successfully resulted in an ACL rupture and associated meniscal injury. The posterior cruciate, lateral collateral, and medial collateral ligaments were intact in all dissected knees. Two weeks after ACL tear, the surgical group showed a significantly higher synovitis score, whereas 8 weeks after ACL tear, the manual group showed a significantly higher volume of osteophytes. No significant differences were found between the groups in terms of OARSI score, anterior tibial translation, range of motion, bone microstructure computed tomography values, and stride distance/irregularity. CONCLUSION: This procedure can be used to create an ACL tear model without causing grossly evident injuries to other ligaments and avoiding the risk of cartilage damage from surgical instruments. CLINICAL RELEVANCE: This procedure offers a more clinically relevant ACL tear model and facilitates simple, inexpensive, and reproducible development of posttraumatic osteoarthritis.

Mesenchymal stem cells derived from adipose tissue and umbilical cord reveal comparable efficacy upon radiation-induced colorectal fibrosis in rats.

Chemoradiotherapy (CRT) and radiotherapy (RT) have served as anticancer treatments and neoadjuvant therapies for conquering multimodal rectal cancers including colorectal carcinoma (CRC), yet the concomitant radiation-induced colorectal fibrosis (RICF) has caused chronic toxicity and stenosis in the colorectal mucosa of patients. Mesenchymal stem/stromal cells (MSCs) with unique bidirectional immunoregulation and anti-fibrotic effect have been recognized as splendid sources for regenerative purposes including intestinal diseases. Herein, we are aiming to verify the feasibility and variations of MSC-based cytotherapy for the remission of RICF from the pathological features and the potential impact upon the transcriptomic signatures of RICF rats. For the purpose, we utilized our well-established RICF Sprague-Dawley (SD) rats by radiation for five weeks, and conducted consecutive intraperitoneal injection of two distinct MSCs for treatment, including MSCs derived from adult adipose tissue (AD-MSCs) and perinatal umbilical cord (UC-MSCs). On the one hand, the efficacy of AD-MSCs and UC-MSCs was assessed by diverse indicators, including weight change, pathological detections (e.g., H&E staining, Masson staining, EVG staining, IF staining, and IHC staining), and proinflammatory and fibrotic factor expression. On the other hand, we turned to RNA-sequencing (RNA-SEQ) and multifaceted bioinformatics analyses (e.g., GOBP, Venn Map, KEGG, and GSEA) to compare the impact of AD-MSC and UC-MSC treatment upon the gene expression profiling and genetic variations. RICF rats after consecutive AD-MSC and UC-MSC administration revealed comparable remission in histopathogenic features and significant suppression of diverse proinflammatory and fibrotic factors expression. Meanwhile, RICF rats after both MSC treatment revealed decrease and variations in the alterations in diverse gene expression and somatic mutations compared to RICF rats. Collectively, our data indicated the comparable therapeutic effect of AD-MSCs and UC-MSCs upon RICF in SD rats, together with the conservations in gene expression profiling and the diverse variations in genetic mutations. Our findings indicated the multifaceted impact of MSC infusion for the supervision of RICF both at the therapeutic and transcriptomic levels, which would provide novel references for the further evaluation and development of MSC-based regimens in future.

Perceived discrimination and youth vaping: The role of intersectional identities.

INTRODUCTION: Electronic cigarettes (also termed e-cigarette or vapes) often contain nicotine, an addictive psychoactive substance, which can have harmful effects during adolescence. Frequent experiences of discrimination are one risk factor shown to increase susceptibility to tobacco use, especially for individuals that identify as a social minority. Applying Intersectionality Theory, this research examined the relationship between youth experiences of discrimination and vape use at the intersection of race/ethnicity and sexual orientation. METHOD: Cross-sectional survey data from 4747 youth (ages 12-17) that participated in the 2022 Teens, Nicotine, and Tobacco Project (TNT) online survey were used to evaluate the impact of discrimination on vape use for lesbian, gay, bisexual, and/or queer/questioning (LGBQ+) youth of color. RESULTS: Multivariable regression analyses showed that identifying as both a sexual and racial/ethnic minority was a risk factor for experiencing discrimination. Frequent discrimination and reporting discrimination due to sexual orientation was associated with a greater likelihood of ever and current vaping. Path models supported that discrimination mediated the relationship between intersectional identity and vape use. LGBQ+ youth of color reported more frequent discrimination, which was associated with a greater likelihood of ever/current vape use. CONCLUSIONS: Intersectionality Theory aids in understanding how discrimination can exacerbate tobacco-related disparities for youth with multiple minority identities. Findings corroborate the importance of measuring discrimination in public health surveys. Effective tobacco interventions could incorporate strategies to cope with discrimination-related stress.

Expression and potential molecular mechanism of TOP2A in metastasis of non-small cell lung cancer.

DNA topoisomerase II alpha (TOP2A) expression, gene alterations, and enzyme activity have been studied in various malignant tumors. Abnormal elevation of TOP2A expression is considered to be related to the development of non-small cell lung cancer (NSCLC). However, its association with tumor metastasis and its mode of action remains unclear. Bioinformatics, real-time quantitative PCR, immunohistochemistry and immunoblotting were used to detect TOP2A expression in NSCLC tissues and cells. Cell migration and invasion assays as well as cytoskeletal staining were performed to analyze the effects of TOP2A on the motility, migration and invasion ability of NSCLC cells. Cell cycle and apoptosis assays were used to verify the effects of TOP2A on apoptosis as well as cycle distribution in NSCLC. TOP2A expression was considerably upregulated in NSCLC and significantly correlated with tumor metastasis and the occurrence of epithelial-mesenchymal transition (EMT) in NSCLC. Additionally, by interacting with the classical ligand Wnt3a, TOP2A may trigger the canonical Wnt signaling pathway in NSCLC. These observations suggest that TOP2A promotes EMT in NSCLC by activating the Wnt/ß-catenin signaling pathway and positively regulates malignant events in NSCLC, in addition to its significant association with tumor metastasis. TOP2A promotes the metastasis of NSCLC by stimulating the canonical Wnt signaling pathway and inducing EMT. This study further elucidates the mechanism of action of TOP2A, suggesting that it might be a potential therapeutic target for anti-metastatic therapy.

Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.

Lung cancer, ranking second globally in both incidence and high mortality among common malignant tumors, presents a significant challenge with frequent occurrences of drug resistance despite the continuous emergence of novel therapeutic agents. This exacerbates disease progression, tumor recurrence, and ultimately leads to poor prognosis. Beyond acquired resistance due to genetic mutations, mounting evidence suggests a critical role of epigenetic mechanisms in this process. Numerous studies have indicated abnormal expression of Histone Methyltransferases (HMTs) in lung cancer, with the abnormal activation of certain HMTs closely linked to drug resistance. HMTs mediate drug tolerance in lung cancer through pathways involving alterations in cellular metabolism, upregulation of cancer stem cell-related genes, promotion of epithelial-mesenchymal transition, and enhanced migratory capabilities. The use of HMT inhibitors also opens new avenues for lung cancer treatment, and targeting HMTs may contribute to reversing drug resistance. This comprehensive review delves into the pivotal roles and molecular mechanisms of HMTs in drug resistance in lung cancer, offering a fresh perspective on therapeutic strategies. By thoroughly examining treatment approaches, it provides new insights into understanding drug resistance in lung cancer, supporting personalized treatment, fostering drug development, and propelling lung cancer therapy into novel territories.

Impact of sex and age on the lateralisation of the tibial tubercle in normal paediatric and adolescent populations.

PURPOSE: Numerous methods have been proposed to characterise tubercle lateralisation. However, their normal values and related changes remain unclear. Accordingly, it was aimed to determine the potential sex and age effects and determined the optimal individualised method of diagnosing lateralisation of the tibial tubercle in patients with recurrent patellar dislocation (RPD). METHODS: Measurements included the tibial tubercle-trochlear groove (TT-TG) distance, tibial tubercle-posterior cruciate ligament (TT-PCL) distance and tibial tubercle lateralisation (TTL); and the proximal tibial width (PTW), trochlear width (TW) and trochlear dysplasia index (TDI), for adjustment. A two-way analysis of variance was used to determine the effect of age, sex and their interaction within the normal group. When the age effect was statistically significant, a nonlinear regression was created. Areas under the receiver-operating characteristic curve (AUCs) were calculated to assess diagnostic accuracy. RESULTS: A total of 277 normal participants (mean [SD] age, 13.5 [2.6] years; 125 [45.1%] female) and 227 patients with RPD (mean [SD] age, 13.5 [2.6] years; 161 [58.1%] female) were analysed. It was found that in the normal group, in patients aged 7-10, TT-PCL distance (p = 0.006), TTL (p = 0.007) and TT-PCL/PTW (p < 0.001) were significantly larger in females than in males. A significant sex effect was also detected on TT-TG/TW (p = 0.014). TT-TG distance, TT-PCL distance, TTL and TT-PCL/PTW (in male patients) approached an established normal adult value of 12.3 mm, 20.9 mm, 0.64 and 0.28, respectively, with increasing age (p < 0.001). The AUC was greater for TT-TG/TDI and TT-TG/TW (p ≤ 0.01) and TT-TG/TDI outperformed TT-TG/TW in patients aged 15-18 (p = 0.004). CONCLUSIONS: Tubercle lateralisation increased with age and was affected by sex, with the exception of TT-TG distance and TT-TG/TDI. TT-TG/TDI is the optimal method of diagnosing a lateralized tibial tubercle in patients with RPD. These findings assist with the evaluation of tubercle lateralisation in that they provide a proper protocol for paediatric and adolescent populations with RPD; and thus, will help determine whether medial tubercle transfer should be included among the tailored surgical procedures considered for the treatment of patients with RPD. LEVEL OF EVIDENCE: Level III.

Integrative physiological, metabolomic, and transcriptomic analysis reveals the drought responses of two apple rootstock cultivars.

BACKGROUND: Drought is considered the main environmental factor restricting apple production and thus the development of the apple industry. Rootstocks play an important role in enhancing the drought tolerance of apple plants. Studies of the physiology have demonstrated that 'ZC9-3' is a strong drought-resistant rootstock, whereas 'Jizhen-2' is a weak drought-resistant rootstock. However, the metabolites in these two apple rootstock varieties that respond to drought stress have not yet been characterized, and the molecular mechanisms underlying their responses to drought stress remain unclear. RESULTS: In this study, the physiological and molecular mechanisms underlying differences in the drought resistance of 'Jizhen-2' (drought-sensitive) and 'ZC9-3' (drought-resistant) apple rootstocks were explored. Under drought stress, the relative water content of the leaves was maintained at higher levels in 'ZC9-3' than in 'Jizhen-2', and the photosynthetic, antioxidant, and osmoregulatory capacities of 'ZC9-3' were stronger than those of 'Jizhen-2'. Metabolome analysis revealed a total of 95 and 156 differentially accumulated metabolites in 'Jizhen-2' and 'ZC9-3' under drought stress, respectively. The up-regulated metabolites in the two cultivars were mainly amino acids and derivatives. Transcriptome analysis revealed that there were more differentially expressed genes and transcription factors in 'ZC9-3' than in 'Jizhen-2' throughout the drought treatment. Metabolomic and transcriptomic analysis revealed that amino acid biosynthesis pathways play key roles in mediating drought resistance in apple rootstocks. A total of 13 metabolites, including L-α-aminoadipate, L-homoserine, L-threonine, L-isoleucine, L-valine, L-leucine, (2S)-2-isopropylmalate, anthranilate, L-tryptophan, L-phenylalanine, L-tyrosine, L-glutamate, and L-proline, play an important role in the difference in drought resistance between 'ZC9-3' and 'Jizhen-2'. In addition, 13 genes encoding O-acetylserine-(thiol)-lyase, S-adenosylmethionine synthetase, ketol-acid isomeroreductase, dihydroxyacid dehydratase, isopropylmalate isomerase, branched-chain aminotransferase, pyruvate kinase, 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase, N-acetylglutamate-5-P-reductase, and pyrroline-5-carboxylate synthetase positively regulate the response of 'ZC9-3' to drought stress. CONCLUSIONS: This study enhances our understanding of the response of apple rootstocks to drought stress at the physiological, metabolic, and transcriptional levels and provides key insights that will aid the cultivation of drought-resistant apple rootstock cultivars. Especially, it identifies key metabolites and genes underlying the drought resistance of apple rootstocks.

Patterns in Tobacco, E-Cigarette, and Cannabis Advertising Exposure Among California Adolescents and Associations With Future Use Expectations.

BACKGROUND: Exposure to tobacco, e-cigarette, or cannabis marketing is associated with adolescent use. Few studies have examined advertising exposure prevalence and patterns across these products concurrently. METHODS: This study assessed past 30-day recalled exposure to promotional messages about tobacco, e-cigarettes ("vapes" on the survey), and cannabis ("marijuana") from various sources among California adolescents (ages 12-17) in the 2022 Teens, Nicotine, and Tobacco Online Survey (N = 2530). Principal components analysis (PCA) was conducted to examine the underlying structure and patterns in advertising exposure sources. Multivariable logistic regression was used to evaluate associations between any advertising exposure and future use expectations (a susceptibility measure) in one year and at age 25 among current never-users. RESULTS: Overall, 65.9% of participants recently noticed at least one tobacco (52.5%), vape (51.5%), or marijuana (45.6%) advertisement. Gas stations or convenience stores were the most common source for tobacco or vape ads; billboards were for marijuana ads. In PCA, advertising exposure patterns correlated with advertising source, not the type of product. Exposures from tobacco-specific sources and nearer point of sale were associated with current use, older age, LGBTQ + identity, and sensation seeking. Among never-users, advertising exposure was associated with one-year and age-25 use expectations for cigarettes (one-year expectations adjusted odds ratio: 1.7; 95% CI: 1.1, 2.5), vapes (2.3; 1.5, 3.5), and marijuana (2.1; 1.5, 3.0). CONCLUSION: California adolescents' exposure to tobacco, e-cigarette, and cannabis marketing is common, follows similar patterns, and is associated with use susceptibility. Comprehensive restrictions on marketing accessible to adolescents could help prevent youth use.

SIRT2-mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma.

ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.

Glutaminase potentiates the glycolysis in esophageal squamous cell carcinoma by interacting with PDK1.

Increasing evidence has demonstrated that glutaminase (GLS) as a key mitochondrial enzyme plays a pivotal role in glutaminolysis, which widely participates in glutamine metabolism serving as main energy sources and building blocks for tumor growth. However, the roles and molecular mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we found that GLS was highly expressed in ESCC tissues and cells. GLS inhibitor CB-839 significantly suppressed cell proliferation, colony formation, migration and invasion of ESCC cells, whereas GLS overexpression displayed the opposite effects. In addition, CB-839 markedly suppressed glucose consumption and lactate production, coupled with the downregulation of glycolysis-related proteins HK2, PFKM, PKM2 and LDHA, whereas GLS overexpression exhibited the adverse results. In vivo animal experiment revealed that CB-839 dramatically suppressed tumor growth, whereas GLS overexpression promoted tumor growth in ESCC cells xenografted nude mice. Mechanistically, GLS was localized in mitochondria of ESCC cells, which interacted with PDK1 protein. CB-839 attenuated the interaction of GLS and PDK1 in ESCC cells by suppressing PDK1 expression, which further evoked the downregulation of p-PDHA1 (s293), however, GLS overexpression markedly enhanced the level of p-PDHA1 (s293). These findings suggest that interaction of GLS with PDK1 accelerates the glycolysis of ESCC cells by inactivating PDH enzyme, and thus targeting GLS may be a novel therapeutic approach for ESCC patients.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

Dysbiosis of gut microbiota and metabolites is associated with radiation-induced colorectal fibrosis and is restored by adipose-derived mesenchymal stem cell therapy.

AIMS: This study aimed to investigate the effects of adipose-derived mesenchymal stem cells (ADSCs) on radiation-induced colorectal fibrosis (RICF) along with the associated dysbiosis of gut microbiota and metabolites. MAIN METHODS: Fecal microbiota were assessed through 16S rRNA gene sequencing, and the fecal metabolome was characterized using liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. The correlation between microbiota and metabolome data was explored. KEY FINDINGS: ADSC injection demonstrated a significant restoration of radiation-induced intestinal damage in vivo. At the phylum level, irradiated rats exhibited an increase in Bacteroidota and Campilobacterota, and a decrease in Firmicutes and Desulfobacterota, contrasting with the ADSC treatment group. Metabolomic analysis revealed 72 differently expressed metabolites (DEMs) from gas chromatography-mass spectrometry and 284 DEMs from liquid chromatography-mass spectrometry in the radiation group compared to the blank group. In the ADSC treatment group versus the radiation group, 36 DEMs from gas chromatography-mass spectrometry and 341 DEMs from liquid chromatography-mass spectrometry were identified. KEGG enrichment analysis implicated pathways such as steroid hormone biosynthesis, gap junction, primary bile acid biosynthesis, citrate cycle, cAMP signaling pathway, and alanine, aspartate, and glutamate metabolism during RICF progression and after treated with ADSCs. Correlation analysis highlighted the role of ADSCs in modulating the metabolic process of Camelledionol in fecal Bacteroides. SIGNIFICANCE: These findings underscore the potential of ADSCs in reversing dysbiosis and restoring normal colonic flora in the context of RICF, offering valuable insights for therapeutic interventions targeting radiation-induced complications.