Clinical sonochemotherapy of inoperable pancreatic cancer using diagnostic ultrasound and microbubbles: a multicentre, open-label, randomised, controlled trial.

OBJECTIVES: Sonochemotherapy, which uses microbubble (MB)-assisted ultrasound (US) to deliver chemotherapeutic agents, has the potential to enhance tumour chemotherapy. The combination of US and MB has been demonstrated to prolong the survival of patients with pancreatic cancer. This phase 2 clinical trial aimed to determine the clinical efficacy and safety of sonochemotherapy for inoperable pancreatic ductal adenocarcinoma by using US and MB. METHODS: Eighty-two patients with stage III or IV pancreatic cancer were recruited from July 2018 to March 2021 and followed up until September 2022. US treatment was performed with a modified diagnostic US scanner for 30 min after chemotherapeutic infusion. The primary endpoint was overall survival (OS), and the secondary endpoints were Eastern Cooperative Oncology Group (ECOG) status < 2, progression-free survival (PFS), disease control rate (DCR), and adverse events. RESULTS: Seventy-eight patients were randomly allocated (40 to chemotherapy and 38 to sonochemotherapy). The median OS was longer with sonochemotherapy than with chemotherapy (9.10 vs. 6.10 months; p = 0.037). The median PFS with sonochemotherapy was 5.50 months, compared with 3.50 months (p = 0.080) for chemotherapy. The time of ECOG status < 2 was longer with sonochemotherapy (7.20 months) than with chemotherapy (5.00 months; p = 0.029). The DCR was 73.68% for sonochemotherapy compared with 42.50% for the control (p = 0.005). The incidence of overall adverse events was balanced between the two groups. CONCLUSIONS: The use of sonochemotherapy can extend the survival and well-being time of stage III or IV pancreatic cancer patients without any increase in serious adverse events. TRIAL REGISTRATION: ChineseClinicalTrials.gov ChiCTR2100044721 CLINICAL RELEVANCE STATEMENT: This multicentre, randomised, controlled trial has proven that sonochemotherapy, namely, the combination of diagnostic ultrasound, microbubbles, and chemotherapy, could extend the overall survival of patients with end-stage pancreatic ductal adenocarcinoma from 6.10 to 9.10 months without increasing any serious adverse events. KEY POINTS: • This is the first multicentre, randomised, controlled trial of sonochemotherapy for clinical pancreatic cancer treatment using ultrasound and a commercial ultrasound contrast agent. • Sonochemotherapy extended the median overall survival from 6.10 (chemotherapy alone) to 9.10 months. • The disease control rate increased from 42.50% with chemotherapy to 73.68% with sonochemotherapy.

Application of Subpatellar Venous Catheter Thrombolysis in Early Acute Lower Extremity Deep Vein Thrombosis.

Objective: To compare the effectiveness and safety of intravenous thrombolysis via the subpatellar vein versus the conventional popliteal vein approach in patients with early acute deep venous thrombosis (DVT) of the lower extremities. Methods: This study included 160 early-stage acute lower extremity DVT patients at our hospital from January 2020 to October 2023, randomly assigned to two groups using sealed envelopes. The control group underwent catheter-directed thrombolysis via the popliteal vein, while the study group received thrombolysis via the subpatellar vein. Surgical parameters, limb circumferences, blood parameters, vein patency, and adverse reactions were evaluated. Results: The study group had longer surgery and X-ray times, as well as a lower urokinase dose compared to the control group (P < .05), with no significant difference in thrombolysis time (P > .05). Thigh and calf circumferences and edema rates didn't significantly change before and after thrombolysis in both groups (P > .05). Hematological parameters, including PT, INR, APTT, FIB, TT, and D-D levels, remained similar between the two groups before and after thrombolysis (P > .05). However, after thrombolysis, both groups showed increased PT, INR, APTT, and TT levels and decreased FIB and D-D levels compared to before thrombolysis (P < .05). Porter scores showed no significant differences between the two groups before thrombolysis (P > .05), but after thrombolysis, both groups had reduced Porter scores, with the study group showing a more pronounced decrease (P < .05). Additionally, the study group had a higher vein patency rate and GCQ score than the control group (P < .05). Adverse reactions occurred at a similar rate in both groups (P > .05). Conclusion: Subpatellar vein catheter-directed thrombolysis offers a safe and more effective alternative to traditional popliteal vein approaches for early acute DVT of the lower extremities, improving outcomes such as vein patency and reducing the need for urokinase.

Impact of focused ultrasound on the ethanol ablation of VX2 liver tumours in rabbits.

OBJECTIVES: In this study, a treatment combining ethanol ablation (EA) and focused ultrasound (FUS) was performed to investigate its synergistic ablation effect on normal liver and VX2 liver tumours in rabbits. METHODS: A total of 59 healthy New Zealand white rabbits were included. For normal liver ablation, 39 animals were treated with FUS alone (n = 12), EA alone (n = 12), EA+FUS combination treatment (n = 12), or the control treatment (n = 3). The other 20 rabbits with implanted VX2 liver tumours were treated with EA alone (n = 10) or EA+FUS (n = 10). For FUS, the liver was exposed to 1 MHz FUS with an intensity of 33.0 W/cm2 (ISPTA) for 20 s. The EA group received an injection of absolute ethanol in the liver or liver tumours. For EA+FUS combination therapy, FUS was focused at the EA injection site, and both methods were carried out at the same time. RESULTS: In normal liver tissues, the ablated volume treated by FUS combined with EA (1.46 ± 0.30 cm3) was approximately 3 times larger than that of EA alone (0.51 ± 0.17 cm3); in VX2 liver tumours, the tumour necrosis rate of the combination therapy was 90.27%, which was much higher than that of EA treatment (63.55%). CONCLUSION: The combination of EA and FUS could effectively increase the liver ablation volume and induce more complete tumour necrosis. KEY POINTS: • This study demonstrated a novel method for enhancing ethanol ablation and elucidated its potential to enhance percutaneous ethanol ablation (PEA) in a simple non-invasive way. • Ethanol excited by focused ultrasound (FUS) exposure tended to accumulate at the injection site, which could prevent ethanol from being washed out by the bloodstream. • The combination of EA and FUS could effectively increase the liver ablation volume and induce more complete tumour necrosis.

Applications of emerging imaging techniques for meat quality and safety detection and evaluation: A review.

With improvement in people's living standards, many people nowadays pay more attention to quality and safety of meat. However, traditional methods for meat quality and safety detection and evaluation, such as manual inspection, mechanical methods, and chemical methods, are tedious, time-consuming, and destructive, which cannot meet the requirements of modern meat industry. Therefore, seeking out rapid, non-destructive, and accurate inspection techniques is important for the meat industry. In recent years, a number of novel and noninvasive imaging techniques, such as optical imaging, ultrasound imaging, tomographic imaging, thermal imaging, and odor imaging, have emerged and shown great potential in quality and safety assessment. In this paper, a detailed overview of advanced applications of these emerging imaging techniques for quality and safety assessment of different types of meat (pork, beef, lamb, chicken, and fish) is presented. In addition, advantages and disadvantages of each imaging technique are also summarized. Finally, future trends for these emerging imaging techniques are discussed, including integration of multiple imaging techniques, cost reduction, and developing powerful image-processing algorithms.

Applications of Computer Vision for Assessing Quality of Agri-food Products: A Review of Recent Research Advances.

With consumer concerns increasing over food quality and safety, the food industry has begun to pay much more attention to the development of rapid and reliable food-evaluation systems over the years. As a result, there is a great need for manufacturers and retailers to operate effective real-time assessments for food quality and safety during food production and processing. Computer vision, comprising a nondestructive assessment approach, has the aptitude to estimate the characteristics of food products with its advantages of fast speed, ease of use, and minimal sample preparation. Specifically, computer vision systems are feasible for classifying food products into specific grades, detecting defects, and estimating properties such as color, shape, size, surface defects, and contamination. Therefore, in order to track the latest research developments of this technology in the agri-food industry, this review aims to present the fundamentals and instrumentation of computer vision systems with details of applications in quality assessment of agri-food products from 2007 to 2013 and also discuss its future trends in combination with spectroscopy.

Effect of microbubble-enhanced ultrasound on percutaneous ethanol ablation of rat walker-256 tumour.

OBJECTIVES: Percutaneous ethanol ablation (PEA) is an effective method for treating small liver cancer. Microbubble-enhanced ultrasound (MEUS) can potentially promote PEA by disrupting the tumour's circulation. In this study, treatment combining MEUS and PEA was performed to find any synergistic effects in tumour ablation. METHODS: Ten rats bearing subcutaneous Walker-256 tumours were treated by MEUS combined with PEA. The other 18 tumour-bearing rats that were treated by MEUS or PEA served as the controls. MEUS was conducted by therapeutic ultrasound (TUS) and microbubble injection. TUS was operated at a frequency of 831 KHz with a pressure amplitude of 4.3 MPa. Tumour blood perfusion was assessed by contrast-enhanced ultrasound (CEUS), and the tumour necrosis rate was determined by histological examination. RESULTS: CEUS showed that the tumour blood perfusion almost vanished in all of the MEUS-treated tumours. The contrast peak intensity dropped 84.8 % in the MEUS + PEA-treated tumours when compared to 46.3 % (p < 0.05) in the PEA-treated tumours 24 h after treatment. The tumour necrosis rate of the combination therapy was 97.50 %, which is much higher than that of the MEUS- (66.2 %) and PEA-treated (81.0 %) tumours. CONCLUSION: PEA combined with MEUS can induce a much more complete tumour necrosis. KEY POINTS: • This experiment demonstrated a novel method for enhancing percutaneous ethanol ablation. • Microbubble-enhanced therapeutic ultrasound is capable of disrupting tumour circulation. • Combined therapy of MEUS and PEA can induce more complete necrosis of tumours.

[Bone marrow mesenchymal stem cells suppress E coli-induced bacterial prostatitis in rats].

OBJECTIVE: To investigate the inhibitory effect of bone marrow mesenchymal stem cells (BMSCs) on E coliinduced prostatitis in rats. METHODS: BMSCs were isolated, cultured and amplified by the attached choice method. Fifty SD rats were randomized into five groups of equal number: normal control, acute bacterial prostatitis (ABP) , chronic bacterial prostatitis (CBP), ABP + BMSCs, and CBP + BMSCs, and the animals in the latter four groups were injected with E. coli into both sides of the prostate under ultrasound guidance for 1 - 14 days to induce ABP and for 4 - 12 weeks to induce CBP. The control rats were injected with the same amount of PBS. Two weeks after injection of BMSCs into the prostates, pathomorphological changes in the prostate were observed under the light microscope and the mRNA and protein levels of IL-1ß and TNF-α determined by RT-PCR and ELISA, respectively, followed by statistical analysis with SPSS 18.0. RESULTS: Histopathological evaluation showed typical pathological inflammatory changes in the prostates of the rats in the ABP and CBP groups, including glandular structural changes, interstitial edema, inflammatory cell infiltration, and fibrous hyperplasia, which were all remarkably relieved after treated with BMSCs. The mRNA and protein levels of IL-ß ([0.829 ± 0.121] and [271.75 ± 90.59] pg/ml) and TNF-α ([0.913 ± 0. 094] and [105.78 ± 19. 05] pg/ml) in the ABP and those of IL-1ß ([0. 975 ± 0. 114] and [265. 31 ± 71. 34] pg/ml) and TNF-α ([0. 886 ± 0. 084] and [107. 45 ± 26. 11 ] pg/ml) in the CBP groups were significantly higher than those in the control rats ([0. 342 ± 0.087] and [45.76 17. 99] pg/ml, P <0. 05); ([0.247 ± 0.054] and ([19.42 ± 7. 75] pg/ml, P <0. 01) as well as than those in the ABP + BMSCs ([0. 433 ± 0. 072] and [51. 34 ± 22. 13] pg/ml, P < 0. 05 ) ; ( [0. 313 ± 0. 076] and [28. 38 ± 8. 78] pg/ml, P < 0. 01) and the CBP + BMSCs group ([0.396 ± 0.064] and [56.37 ± 21.22] pg/ml, P <0.05); ([0.417 ± 0.068] and [29.21 ± 10.22] pg/ml, P <0.01). CONCLUSION: Injection of BMSCs can reduce E coli-induced prostatic inflammation reaction, which.may be associated with its reduction of inflammatory cell infiltration and the expressions of IL-1ß and TNF-α in the prostate tissue.

Efficacy of neonatal HBV vaccination on liver cancer and other liver diseases over 30-year follow-up of the Qidong hepatitis B intervention study: a cluster randomized controlled trial.

BACKGROUND: Neonatal hepatitis B vaccination has been implemented worldwide to prevent hepatitis B virus (HBV) infections. Its long-term protective efficacy on primary liver cancer (PLC) and other liver diseases has not been fully examined. METHODS AND FINDINGS: The Qidong Hepatitis B Intervention Study, a population-based, cluster randomized, controlled trial between 1985 and 1990 in Qidong, China, included 39,292 newborns who were randomly assigned to the vaccination group in which 38,366 participants completed the HBV vaccination series and 34,441 newborns who were randomly assigned to the control group in which the participants received neither a vaccine nor a placebo. However, 23,368 (67.8%) participants in the control group received catch-up vaccination at age 10-14 years. By December 2013, a total of 3,895 (10.2%) in the vaccination group and 3,898 (11.3%) in the control group were lost to follow-up. Information on PLC incidence and liver disease mortality were collected through linkage of all remaining cohort members to a well-established population-based tumor registry until December 31, 2013. Two cross-sectional surveys on HBV surface antigen (HBsAg) seroprevalence were conducted in 1996-2000 and 2008-2012. The participation rates of the two surveys were 57.5% (21,770) and 50.7% (17,204) in the vaccination group and 36.3% (12,184) and 58.6% (17,395) in the control group, respectively. Using intention-to-treat analysis, we found that the incidence rate of PLC and the mortality rates of severe end-stage liver diseases and infant fulminant hepatitis were significantly lower in the vaccination group than the control group with efficacies of 84% (95% CI 23%-97%), 70% (95% CI 15%-89%), and 69% (95% CI 34%-85%), respectively. The estimated efficacy of catch-up vaccination on HBsAg seroprevalence in early adulthood was 21% (95% CI 10%-30%), substantially weaker than that of the neonatal vaccination (72%, 95% CI 68%-75%). Receiving a booster at age 10-14 years decreased HBsAg seroprevalence if participants were born to HBsAg-positive mothers (hazard ratio [HR]  = 0.68, 95% CI 0.47-0.97). Limitations to consider in interpreting the study results include the small number of individuals with PLC, participants lost to follow-up, and the large proportion of participants who did not provide serum samples at follow-up. CONCLUSIONS: Neonatal HBV vaccination was found to significantly decrease HBsAg seroprevalence in childhood through young adulthood and subsequently reduce the risk of PLC and other liver diseases in young adults in rural China. The findings underscore the importance of neonatal HBV vaccination. Our results also suggest that an adolescence booster should be considered in individuals born to HBsAg-positive mothers and who have completed the HBV neonatal vaccination series. Please see later in the article for the Editors' Summary.

[Long optical path gas detection based on MEMS infrared light source].

According to the requirements of infrared gas sensor for the light source, a broad wavelength, high modulation frequency, low power consumption and small size MEMS infrared light source is chosen as the radiation source, whose performance meets the requirements of infrared sensing system for the light source greatly. However, the infrared light source with the lamberation radiation characteristics is a surface light source, which is still with a large numerical aperture after shaping. It is difficult to increase the detection sensitivity by using a traditional long optical gas cell in a MEMS infrared light source detection system. Based on the dual-wavelength single beam differential detection method, an integrating sphere as the gas cell for long optical path is designed, which is able to realize long optical path for high sensitivity gas detection. The physical dimension is deduced for the equivalent optical path according to the flux conservation principle in the process of light transmission, solving the calculation problem of equivalent optical path of the integrating sphere cell. Using FPGA control chip, the MEMS infrared light source is droved at high frequency modulation and the detector output signal is processed, which makes the external circuit design much simple and flexible. It turns out that 166.7 cm equivalent optical path and the minimum concentration of methane of 0.001 x 10(-6) are achieved by the use of a 5 cm diameter integrating sphere in the research, improving the sensitivity of infrared detection system greatly.

[Laser speckle suppression due to dynamic multiple scattering scheme introduced by oblique incidence].

Speckle suppression has been the research focus in laser display technology. In the present paper, the relation between multiple scattering and the size of speckle grains is established by analyzing the properties of speckle generated by the laser beam through SiO2 suspension. Combined with dynamic light scattering theory, laser speckle suppression due to dynamic multiple scattering scheme introduced by oblique incidence is proposed. A speckle suppression element consists of a static diffuser and a light pipe containing the water suspension of SiO2 microspheres with a diameter of 300 nm and a molar concentration of 3.0 x 10(-4) µm3, which is integrated with the laser display system. The laser beam with different incident angles into the SiO2 suspension affecting the contrast of the speckle images is analyzed by the experiments. The results demonstrate that the contrast of the speckle image can be reduced to 0.067 from 0.43 when the beam with the incident angle of approximately 8 degrees illuminates into the SiO2 suspension. The spatial average of speckle granules and the temporal average of speckle images were achieved by the proposed method, which improved the effect of speckle suppression. The proposed element for speckle suppression improved the reliability and reduced the cost of laser projection system, since no mechanical vibration is needed and it is convenient to integrate the element with the existing projection system.

Physicochemical, structural and functional properties of pomelo peel pectin extracted by combination of pulsed electric field and cellulase hydrolysis.

In this study, pectin extracted from pomelo peel was investigated using three different combination methods of pulsed electric field (PEF) and cellulase. Three action sequences were performed, including PEF treatment followed by enzymatic hydrolysis, enzymatic hydrolysis followed by PEF treatment, and enzymatic hydrolysis simultaneously treated by PEF. The three corresponding pectins were namely PEP, EPP and SP. The physiochemical, molecular structural and functional properties of the three pectins were determined. The results showed that PEP had excellent physiochemical properties, with the highest yield (12.08 %), total sugar (80.17 %) and total phenol content (38.20 %). The monosaccharide composition and FT-IR analysis indicated that the three pectins were similar. The molecular weights of PEP, EPP and SP were 51.13, 88.51 and 40.00 kDa, respectively. PEP showed the best gel properties, emulsification stability and antioxidant capacity among the three products, due to its high galacturonic acid and total phenol content, appropriate protein and low molecular weight. The mechanism of PEF-assisted cellulase hydrolysis of pomelo peel was also revealed by SEM analysis. These results suggested that PEF pretreatment was the best method, which not only improved the efficiency of enzymatic extraction, but also reduced resource waste and increased financial benefits.

Correlation of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with serum α-klotho levels in US middle-aged and older individuals: Results from NHANES 2007-2016.

Background: The α-klotho (αKl) is widely accepted as an anti-aging and anti-inflammatory protein. However, it is rarely reported on the function and mechanism of αKl in the overall population (including healthy people and those with history of chronic disease). The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are established as predictors of systemic inflammation. This study aims to investigate the relationship between NLR, PLR, and αKl levels in the overall population. Methods: Data from 10,124 adults aged 40 years old and above, collected from NHANES 2007-2016, were analyzed. Associations between NLR, PLR, and αKl levels were assessed by weighted multivariate linear regression analyses, adjusting for potential confounders. Subgroup analysis was conducted by gender, age, diabetes, cardiovascular disease, and chronic kidney disease. Results: Weighted linear regression models showed that a significant negative correlation was observed between both NLR and PLR with αKl levels. Subgroup analysis revealed that the negative correlation between NLR and serum αKl levels was not significant in individuals aged 40-59 years and males, while this relationship remained stable across most other subgroups. The negative correlation between PLR and serum αKl levels was consistent across most subgroups but not significant in individuals with cardiovascular disease. Conclusion: Our study revealed a significant negative relationship between inflammatory markers (NLR and PLR) and serum αKl levels, suggesting systemic inflammation may be linked to reduced αKl expression. Subgroup analyses showed that the relationship varies across different demographic and health-related factors. We provided insight into the significance of managing inflammation and preserving αKl levels.

Synthesis, structural characterization and in vitro digestion stability of a soluble soybean polysaccharide­zinc chelate.

The chelation reaction of soluble soybean polysaccharide (SSPS) with zinc was investigated. Using response surface methodology, the optimum parameters for SSPS-Zn synthesis were obtained: pH 5.3, SSPS-ZnCl2 mass ratio of 9.44:1, reaction temperature 50.44 °C, and reaction time 1.5 h, with the highest zinc content of 24.73 %. Compared with SSPS, SSPS-Zn increased in rhamnogalacturonan content and decreased in that of neutral monosaccharides (Fuc, Ara, Gal, Glu and Xyl). UV-vis spectra indicated that SSPS-Zn was lower than SSPS in protein content. FTIR spectra indicated that CO group of SSPS was bonded to Zn2+. X-ray diffraction spectra demonstrated that SSPS-Zn had higher crystallinity. Congo red reactions showed that SSPS possessed a triple-helix conformation while SSPS-Zn formed an irregular free-coiled conformation. EDX confirmed SSPS-Zn synthesis successfully. TGA curves exhibited that SSPS-Zn required higher temperature to undergo degradation. AFM revealed that SSPS-Zn was clustered while SSPS was filamentous. SEM micrographs showed the cracked fragments on the surface of SSPS-Zn. By in vitro simulation of gastrointestinal digestion, Zn2+ release reached 68.87 % after 2 h digestion. Consequently, the chelation of SSPS with zinc could change structure and provide a basis for research and application of novel zinc supplements.

Pulsed electric field enhances glucose glycation and emulsifying properties of bovine serum albumin: Focus on polarization and ionization effects at a high reaction temperature.

Previous studies demonstrated that the non-thermal effects of pulsed electric fields can promote protein glycation below 40 °C, but it does not always enhance the emulsifying properties of proteins, such as in the bovine serum albumin/glucose model. Therefore, the aim of this study was to investigate the impact of non-thermal effects on the glucose glycation and emulsification properties of bovine serum albumin at 90 °C. The results of circular dichroism, surface hydrophobicity, and molecular dynamics simulations showed that the polarization effect increased the degree of glycation of bovine serum albumin-glucose conjugates from 12.82 % to 21.10 % by unfolding protein molecule, while the emulsifying stability index was increased from 79.17 to 100.73 compared with the control. Furthermore, the results of principal component analysis and Pearson correlation analysis indicated that the ionization effect and the free radicals generated by pulsed electric fields significantly (p < 0.05) inhibited browning and reduced free sulfhydryl content. This study demonstrated that pulsed electric fields combined with heating can prepare glycated proteins with good emulsifying properties in a short period of time and at temperatures lower than conventional heating while reducing energy consumption. This processing strategy has potential applications in improving the emulsifying performance of highly stable proteins.

EHMT2 affects microglia polarization and aggravates neuronal damage and inflammatory response via regulating HMOX1.

Objective: This research was designed to ascertain the function of euchromatic histone lysine methyltransferase 2 (EHMT2) in ischemic stroke-induced neuronal damage and inflammatory response and its regulatory mechanism. Methods: Mouse microglia (BV-2 cells) were induced by oxygen glucose deprivation/reoxygenation (OGD/R) to establish a cellular model, and then co-cultured with HT22 hippocampal neurons. After that, HT22 cell viability and apoptosis were evaluated, followed by the measurement of apoptosis-related factors (B-cell lymphoma-2, Bcl-2 associated X, and cleaved-Caspase 3). Meanwhile, the expression of inducible nitric oxide synthase (M1 microglia polarization marker) and arginase 1 (M2 microglia polarization marker) in BV-2 cells was detected, as well as the levels of inflammatory factors (tumor necrosis factor-α, interleukin [IL]-6, IL-10, IL-1ß, and IL-4). Additionally, the expression of EHMT2 and heme oxygenase 1 (HMOX1) in BV-2 cells was assessed by quantitative reverse transcription polymerase chain reaction and western blot, and the binding between EHMT2 and HMOX1 was predicted and verified. Results: OGD/R treatment led to decreased cell viability and increased cell apoptosis in HT22 cells, and aggravated inflammatory response in BV-2 cells. In OGD/R-induced BV-2 cells, EHMT2 and HMOX1 were increasingly expressed, and knockdown of EHMT2 or HMOX1 in BV-2 cells could inhibit neuronal damage and inflammatory response. Moreover, EHMT2 promoted HMOX1 transcription level by histone methylation. Conclusion: Collected evidence showed that down-regulation of EHMT2 relieved neuronal damage and inflammatory response by inhibiting HMOX1 expression.

5-lipoxygenase as a target to sensitize glioblastoma to temozolomide treatment via ß-catenin-dependent pathway.

Sensitizing strategy is required to improve the clinical management of glioblastoma (GBM). 5-Lipoxygenase (Alox5) has been recently garnered attention due to its pro-carcinogenic roles in various cancers. This study demonstrates that Alox5 is overexpressed in GBM but not normal neuronal tissues. Alox5 depletion inhibits the growth of GBM cells, both in bulky and stem-like populations, and enhances the anti-cancer effects of temozolomide. The mechanism behind this involves a decrease in ß-catenin level and activity upon Alox5 depletion. The inhibitory effects of Alox5 can be reversed by the addition of a Wnt agonist. Additionally, the study reveals that zileuton, an Alox5 inhibitor approved for asthma treatment, significantly improves the efficacy of temozolomide in mice without causing toxicity. Combination index analysis clearly demonstrates that zileuton and temozolomide act synergistically. These findings highlight the importance of Alox5 as a critical regulator of glioblastoma sensitivity and suggest the potential repurposing of zileuton for GBM treatment.

CBX8 Promotes Cell Proliferation and Metastasis and Leads to Radiotherapy Tolerance of Glioma Cells.

AIM: To illustrate the role of CBX8 -a protein involved in protein metabolism and chromatin regulation/acetylation- in glioma cells, especially in DNA damage repair pathways. MATERIAL AND METHODS: Detect CBX8 expression in glioma cells and clinical samples by qPCR and Western blot. Overexpression and knockdown CBX8 cell lines were constructed by lentivirus infection. CCK8, wound healing, and transwell assays were used to verify the effects of CBX8 on proliferation, migration, and invasion of glioma cells. After radiation treatment, CCK8 and colony formation assays were used to detect cell sensitivity of CBX8 expression levels to radiotherapy. Western blot detected expression levels of p-ATM, p-ATR, BRCA-1, RAD51, and P53 in various cells after radiation treatment, demonstrating CBX8?s effect on DNA damage and repair proteins. Finally, the sensitivity of tumors with different CBX8 expression levels to radiotherapy was verified in vivo. RESULTS: CBX8 expression is significantly increased in glioma. High CBX8 expression promotes proliferation, invasion, and migration of glioma cells. It also causes glioma cells to resist radiotherapy. CBX8 affects protein expression related to DNA damage repair. In vivo, tumors with low CBX8 expression are more sensitive to radiotherapy. CONCLUSION: CBX8 promotes proliferation and metastasis of glioma cells and reduces cell sensitivity to radiotherapy by affecting DNA damage repair pathways.

Low Wall Shear Stress and High Intra-aneurysmal Pressure are Associated with Ruptured Status of Vertebral Artery Dissecting Aneurysms.

PURPOSE: The morphological and hemodynamic features of patients with vertebral artery dissecting aneurysms (VADAs) are yet unknown. This study sought to elucidate morphological and hemodynamic features of patients with ruptured and unruptured VADAs based on computed flow simulation. METHODS: Fifty-two patients (31 unruptured and 21 ruptured VADAs) were admitted to two hospitals between March 2016 and October 2021. All VADAs were located in the intradural segment, and their clinical, morphological, and hemodynamic parameters were retrospectively analyzed. The hemodynamic parameters were determined through computational fluid dynamics simulations. Univariate statistical and multivariable logistic regression analyses were employed to select significantly different parameters and identify key factors. Receiver operating characteristic (ROC) analysis was used to assess the discrimination for each key factor. RESULTS: Four hemodynamic parameters were observed to significantly differ between ruptured and unruptured VADAs, including wall shear stress (WSS), low shear area, intra-aneurysmal pressure (IAP), and relative residence time. However, no significant differences were observed in morphological parameters between ruptured and unruptured VADAs. Multivariable logistic regression analysis revealed that low WSS and high IAP were significantly observed in the ruptured VADAs and demonstrated adequate discrimination. CONCLUSIONS: This research indicates significant hemodynamic differences, but no morphological differences were observed between ruptured and unruptured VADAs. The ruptured group had significantly lower WSS and higher IAP than the unruptured group. To further confirm the roles of low WSS and high IAP in the rupture of VADAs, large prospective studies and long-term follow-up of unruptured VADAs are required.

Valorizing protein-polysaccharide conjugates from sugar beet pulp as an emulsifier.

Inspired by the emulsion stability of sugar beet pulp pectin, the hydrophobic protein fraction in sugar beet pulp (SBP) is expected to feature high interfacial activity. This work retrieved alkaline extracted protein-polysaccharide conjugates (AEC) from partially depectinized SBP by hot alkaline extraction. AEC was protein-rich (57.20 %), and the polysaccharide mainly comprised neutral sugar, which adopted a rhamnogalacturonan-I pectin-like structure. The hydrophobic polypeptide chains tangled as a dense 'core' with polysaccharide chains attached as a hydrated 'shell' (hydrodynamic radius of ~110 nm). AEC could significantly decrease the oil-water interfacial tension (11.58 mN/m), featuring superior emulsification performance than three control emulsifiers, especially the excellent emulsifying stability (10 % oil) as the emulsion droplet size of 0.438 and 0.479 µm for fresh and stored (60 °C, 5 d) emulsions, respectively. The relationship of molecular structure to emulsification was investigated by specific enzymic modification, suggesting the intact macromolecular structure was closely related to emulsifying activity and that the NS fraction contributed greatly to emulsifying stability. Moreover, AEC was highly efficient to stabilize gel-like high internal phase emulsions (oil fraction 0.80) with low concentration (0.2 %) and even high ionic strength (0-1000 mM). Altogether, valorizing AEC as an emulsifier is feasible for high-value utilization of SBP.

Thermomechanically micronized sugar beet pulp: Emulsification performance and the contribution of soluble elements and insoluble fibrous particles.

In this work, thermomechanically micronized sugar beet pulp (MSBP), a micron-scaled plant-based byproduct comprised of soluble elements (∼40 wt%) and insoluble fibrous particles (IFPs, ∼60 wt%), was used as a sole stabilizer for oil-in-water emulsion fabrication. The influence of emulsification parameters on the emulsifying properties of MSBP was investigated, including emulsification techniques, MSBP concentration, and oil weight fraction. High-speed shearing (M1), ultrasonication (M2), and microfludization (M3) were used to fabricate oil-in-water emulsions (20% oil) with 0.60 wt% MSBP as stabilizer, in which the d4,3 value was 68.3, 31.5, and 18.2 µm, respectively. Emulsions fabricated by M2 and M3 (higher energy input) were more stable than M1 (lower energy input) during long-term storage (30 days) as no significant increase of d4,3. As compared to M1, the adsorption ratio of IFPs and protein was increased from ∼0.46 and ∼0.34 to ∼0.88 and ∼0.55 by M3. Fabricated by M3, the creaming behavior of emulsions was completely inhibited with 1.00 wt% MSBP (20% oil) and 40% oil (0.60 wt% MSBP), showing a flocculated state and could be disturbed by sodium dodecyl sulfate. The gel-like network formed by IFPs could be strengthened after storage as both viscosity and module were significantly increased. During emulsification, the co-stabilization effect of the soluble elements and IFPs enabled a compact and hybrid coverage onto the droplet surface, which acted as a physical barrier to endow the emulsion with robust steric repulsion. Altogether, these findings suggested the feasibility of using plant-based byproducts as oil-in-water emulsion stabilizers.