Topology Optimization Driven Bone-Remodeling Simulation for Lumbar Interbody Fusion.

This study proposes a numerical approach for simulating bone remodeling in lumbar interbody fusion (LIF). It employs a topology optimization method to drive the remodeling process and uses a pixel function to describe the structural topology and bone density distribution. Unlike traditional approaches based on strain energy density or compliance, this study adopts von Mises stress to guide the remodeling of LIF. A novel pixel interpolation scheme associated with stress criteria is applied to the physical properties of the bone, directly addressing the stress shielding effect caused by the implanted cage, which significantly influences the bone remodeling outcome in LIF. Additionally, a boundary inverse approach is utilized to reconstruct a simplified analysis model. To reduce computational cost while maintaining high structural resolution and accuracy, the Scaled Boundary Finite Element Method (SBFEM) is introduced. The proposed numerical approach successfully generates results that closely resemble human lumbar interbody fusion.

Qualitative and quantitative diagnosis of intramuscular hemangioma subtypes: Diagnostic performance comparison of ESWAN and conventional MRI.

BACKGROUND: Preoperative identification of intramuscular hemangioma (IMH) subtypes (capillary hemangioma, cavernous hemangioma, and mixed hemangioma) is urgently necessary. Enhanced T2*-weighted angiography (ESWAN) is sensitive to vessels and metabolites and can be used to diagnose IMH subtypes. PURPOSE: To compare the diagnostic performances of ESWAN and conventional magnetic resonance imaging (MRI) for qualitative and quantitative diagnosis of IMH subtypes. MATERIAL AND METHODS: In total, 23 patients with IMHs were examined using conventional MRI and ESWAN. The signal intensity ratios (SIRs) of conventional MRI and ESWAN were measured. RESULTS: There was no significant difference for volume among the three subtypes (P = 0.124, P = 0.145). Various shapes and MRI signals were shown in the three subtypes of IMH. There was no significant difference for SIRs of conventional MRI (P = 0.558, P = 0.259, P = 0.385, P = 0.347). However, there was a significant difference for SIRs of ESWAN parameters (P = 0.050, P < 0.001, P = 0.005, P = 0.002). Capillary hemangiomas can be diagnosed when R2* SIR is <0.912 and intratumoral susceptibility signal (ITSS) percentage is <29.085%. Cavernous hemangiomas should be considered when R2* SIR is >0.912, ITSS percentage >35.226%, and phase SIR >2.536. In addition, mixed hemangiomas should be considered when T2* SIR is >0.662 and R2* SIR <1.618. CONCLUSION: Conventional MRI can only display the volume, shape, and signal of IMHs. 3D-MinIP imaging of ESWAN can show the veins and minor hemorrhage. SIRs of ESWAN parameters including T2* value, R2* value, phase value, and percentage of ITSS can be used to quantitatively diagnose capillary hemangiomas, cavernous hemangiomas, and mixed hemangiomas.

Protection of pancreatic ß-cell by phosphocreatine through mitochondrial improvement via the regulation of dual AKT/IRS-1/GSK-3ß and STAT3/Cyp-D signaling pathways.

Diabetes mellitus (DM) is a metabolic syndrome, caused by insufficient insulin secretion or insulin resistance (IR). DM enhances oxidative stress and induces mitochondrial function in different kinds of cell types, including pancreatic ß-cells. Our previous study has showed phosphocreatine (PCr) can advance the mitochondrial function through enhancing the oxidative phosphorylation and electron transport ability in mitochondria damaged by methylglyoxal (MG). Our aim was to explore the potential role of PCr as a molecule to protect mitochondria from diabetes-induced pancreatic ß-cell injury with insulin secretion deficiency or IR through dual AKT/IRS-1/GSK-3ß and STAT3/Cyclophilin D (Cyp-D) signaling pathways. MG-induced INS-1 cell viability, apoptosis, mitochondrial division and fusion, the morphology, and function of mitochondria were suppressed. Flow cytometry was used to detect the production of intracellular reactive oxygen species (ROS) and the changes of intracellular calcium, and the respiratory function was measured by oxygraph-2k. The expressions of AKT, IRS-1, GSK-3ß, STAT3, and Cyp-D were detected using Western blot. The result showed that the oxidative stress-related kinases were significantly restored to the normal level after the pretreatment with PCr. Moreover, PCr pretreatment significantly inhibited cell apoptosis, decreased intracellular calcium, and ROS production, and inhibited mitochondrial division and fusion, and increased ATP synthesis damaged by MG in INS-1 cells. In addition, pretreatment with PCr suppressed Cytochrome C, p-STAT3, and Cyp-D expressions, while increased p-AKT, p-IRS-1, p-GSK-3ß, caspase-3, and caspase-9 expressions. In conclusion, PCr has protective effect on INS-1 cells in vitro and in vivo, relying on AKT mediated STAT3/ Cyp-D pathway to inhibit oxidative stress and restore mitochondrial function, signifying that PCr might become an emerging candidate for the cure of diabetic pancreatic cancer ß-cell damage.

Orthognathic Surgery in Invisalign Patients.

ABSTRACT: Orthodontic treatment combined with orthognathic surgery is frequently necessary to effectively manage patients suffering from severe craniofacial deformities. Brackets and wires are conventionally utilized for intraoperative splint stabilization in conventional orthognathic surgery, but such an approach is not applicable for patients undergoing treatment using clear aligners (the Invisalign system). The purpose of this article is to discuss the relative advantages, disadvantages, and challenges of using the Invisalign system when treating severe skeletal crossbite relative to cases treated using conventional braces. The case of this article described a 19-year-old male with skeletal class III crossbite undergoing planned Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO). For this patient, pre- and post-surgical orthodontics were conducted using an Invisalign system, with the interim and final splints being fixed to eight 8 mm mini-screws. Overall, this article reveals that the Invisalign system can be effectively employed for orthodontic treatment in combination with orthognathic surgery.

Ribosome assembly factor URB1 contributes to colorectal cancer proliferation through transcriptional activation of ATF4.

Ribosome assembly factor URB1 is essential for ribosome biogenesis. However, its latent role in cancer remains unclear. Analysis of The Cancer Genome Atlas database and clinical tissue microarray staining showed that URB1 expression was upregulated in colorectal cancer (CRC) and prominently related to clinicopathological characteristics. Silencing of URB1 hampered human CRC cell proliferation and growth in vitro and in vivo. Microarray screening, ingenuity pathway analysis, and JASPAR assessment indicated that activating transcription factor 4 (ATF4) and X-box binding protein 1 (XBP1) are potential downstream targets of URB1 and could transcriptionally interact through direct binding. Silencing of URB1 significantly decreased ATF4 and cyclin A2 (CCNA2) expression in vivo and in vitro. Restoration of ATF4 effectively reversed the malignant proliferation phenotype of URB1-silenced CRC cells. Dual-luciferase reporter and ChIP assays indicated that XBP1 transcriptionally activated ATF4 by binding with its promoter region. X-box binding protein 1 colocalized with ATF4 in the nuclei of RKO cells, and ATF4 mRNA expression was positively regulated by XBP1. This study shows that URB1 contributes to oncogenesis and CRC growth through XBP1-mediated transcriptional activation of ATF4. Therefore, URB1 could be a potential therapeutic target for CRC.

Organic Materials as Electrodes in Potassium-Ion Batteries.

The integrated advantages of organic electrode materials and potassium metal make the organic potassium-ion batteries (OPIBs) promising secondary batteries. This review summarizes the latest research progress on OPIBs according to the different types of electrode materials (namely, organic small molecules compounds, polymers, and frameworks (metal-organic frameworks (MOFs), covalent organic frameworks (COFs)). Additionally, the research prospects and outlook for OPIBs are also provided.

Comparison of three-dimensional versus two-dimensional laparoscopic surgery for rectal cancer: a meta-analysis.

PURPOSE: Three-dimensional (3D) vision technology has recently been validated for the improvement of surgical skills in a simulated setting. This study assessed the current evidence regarding the efficiency and potential advantages of 3D compared with two-dimensional (2D) laparoscopic rectal surgery for rectal cancer. METHODS: We comprehensively searched PubMed, EMBASE and the Cochrane Library and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) and non-randomized controlled trials (nRCTs) assessing the two approaches. RESULTS: Four trials including a total 331 cases were identified. The positive circumferential resection margins (CRMs) were significantly lower for the 3D group (P = 0.02). The operative time was significantly shorter in the 3D group than in the 2D group (P < 0.00001). There was less estimated blood loss (EBL) in the 3D group than in the 2D group (P = 0.02). Perioperative complication rates, conversion rate, harvested lymph nodes, first flatus, length of stay, pneumonia, wound infection, ileus, anastomotic fistula and urinary retention did not differ significantly between the two groups (P > 0.05). CONCLUSIONS: In summary, 3D laparoscopic rectal surgery appears to have advantages over 2D laparoscopic rectal surgery in terms of positive CRM and operation time; however, it is not better than 2D laparoscopic rectal surgery in terms of the conversion rate and postoperative complications.

Robotic Versus Laparoscopic Rectal Surgery for Rectal Cancer: A Meta-Analysis of 7 Randomized Controlled Trials.

Background. Robotic surgery has been recently used as a novel tool for rectal surgery. This study assessed the current evidence regarding the efficiency, safety, and potential advantages of robotic rectal surgery (RRS) compared with laparoscopic rectal surgery (LRS). Methods. We comprehensively searched PubMed, Embase, and the Cochrane Library databases and performed a systematic review and cumulative meta-analysis of all randomized controlled trials (RCTs) assessing the 2 approaches. Results. Seven RCTs including a total of 1022 cases were identified. The conversion rate is significantly lower for RRS (odds ratio: 0.29; 95% confidence interval: 0.09 to 0.96; P = .04). The length of the distal margin was significantly shorter in the LRS group than in the RRS group (weighted mean difference: 0.60; 95% confidence interval: 0.09 to 1.10; P = .02). Perioperative complication rates, harvested lymph nodes, positive circumferential resection margins, complete total mesorectal excision, first flatus, and length of stay did not differ significantly between approaches (P > .05). Conclusions. This meta-analysis indicates that RRS is a safe and effective approach. It is not inferior to LRS in terms of oncologic outcomes and postoperative complications. Future large-volume, well-designed RCTs with extensive follow-up are awaited to confirm and update the findings of this analysis.

Diffusion-weighted imaging in relation to morphology on dynamic contrast enhancement MRI: the diagnostic value of characterizing non-puerperal mastitis.

OBJECTIVES: To demonstrate the value of diffusion-weighted imaging (DWI) in the characterisation of mastitis lesions. METHODS: Sixty-one non-puerperal patients with pathologically confirmed single benign mastitis lesions underwent preoperative examinations with conventional MRI and axial DWI. Patients were categorised into three groups: (1) periductal mastitis (PDM), (2) granulomatous lobular mastitis (GLM), and (3) infectious abscess (IAB). Apparent diffusion coefficient (ADC) values of each lesion were recorded. A one-way ANOVA with logistic analysis was performed to compare ADC values and other parameters. Discriminative abilities of DWI modalities were compared using the area under the receiver operating characteristic curve (AUC). P < 0.05 was considered statistically significant. RESULTS: ADC values differed significantly among the three groups (P = 0.003) as well as between PDM and IAB and between PDM and GLM. The distribution of non-mass enhancement on dynamic contrast-enhanced (DCE) MRI differed significantly among the three groups (P = 0.03) but not between any two groups specifically. There were no differences in lesion location, patient age, T2WI or DWI signal intensity, enhancement type, non-mass internal enhancement, or mass enhancement characteristics among the three groups. CONCLUSIONS: ADC values and the distribution of non-mass enhancement are valuable in classifying mastitis subtypes. KEY POINTS: • Mastitis subtypes exhibit different characteristics on DWI and DCE MRI. • ADC values are helpful in isolating PDM from other mastitis lesions. • Distribution of non-mass enhancement also has value in comparing mastitis subtypes.

A pilot evaluation of magnetic resonance imaging characteristics seen with solid papillary carcinomas of the breast in 4 patients.

BACKGROUND: Solid papillary carcinoma (SPC) is a rare variant of breast papillary carcinoma with unique pathological morphology and biological behavior. There is only one case report on T1-MRI of SPC. In this study, we report our findings on this new category of papillary carcinoma to fill the gap in MRI characterization of SPC. METHODS: This retrospective study included four pathology-confirmed in situ SPC patients. Conventional MRI, diffusion weighted imaging (DWI), and magnetic resonance spectroscopy (MRS) were performed with a 1.5 T whole-body MR scanner before surgical operation. The following characteristics of each lesion were recorded: signal intensity on T2WI/STIR and T1FSPGR, morphology, maximum lesion size, and time intensity curve (TIC) on dynamic contrast enhancement MRI (DCE-MRI), apparent diffusion coefficient (ADC) value from DWI, and Cho peak from MRS. RESULTS: Signal intensities of all lesions were heterogenous on T2WI/STIR and T1FSPGR. Mass enhancements were observed for all lesions with either oval or irregular shapes on DCE-MRI. The maximum lesion size ranged from 0.8 cm to 3.2 cm. All lesion margins were circumscribed, and internal enhancements were homogeneous or heterogeneous from DCE-MRI. TIC appeared with a rapid increase in initial contrast phases of all lesions. All lesions on DWI (b = 1000s/mm2) were slightly hyperintense with an ADC value range of 1.3 × 10-3 mm2/s to 1.9 × 10-3 mm2/s. Cho peak was absent at 3.2 ppm for all lesions. CONCLUSIONS: MRI characteristics of SPC include heterogeneous signal intensity within the lesion on T2WI/STIR and T1FSPGR, mass enhancement with circumscribed margins, either oval or irregular shapes, and a rapid initial enhancement of TIC on DCE-MRI. ADC values and the absence of Cho peak may provide valuable information to distinguish SPC from other invasive breast carcinomas.

Simultaneous quantification of Escherichia coli O157:H7 and Shigella boydii using a visual-antibody-macroarray.

Being high throughput, rapid, automated, economical, convenient to operate and highly sensitive, protein arrays have been widely used in the analysis of tumor markers and veterinary drug residues. Pathogenic microbes also can be detected qualitatively by DNA array or protein array; however, their high throughput detection and quantification remains a big obstacle. To evaluate the potentiality of protein arrays for multiple quantitative detection of microorganisms with naked eye examination without the help of any equipment, here we developed a visual-antibody-macroarray (VAMA) aiming at rapid and simultaneous quantification of Escherichia coli O157:H7 and Shigella boydii. The results show that this VAMA is highly specific and is able to distinguish mixed Escherichia coli O157:H7 and Shigella boydii synchronously. The detection limits are equivalent to 3.4 × 10(5) CFU mL(-1) and 3.2 × 10(5) CFU mL(-1), respectively, which conform to the results of plate counting and ELISA. Importantly, the examination can be solely performed with the naked eye. Therefore, we provide an easy, reliable and rapid method for quantitative analysis of microorganisms.

Unenhanced respiratory-gated magnetic resonance angiography (MRA) of renal artery in hypertensive patients using true fast imaging with steady-state precession technique compared with contrast-enhanced MRA.

OBJECTIVE: This study was aimed to evaluate the accuracy of "True Fast Imaging with Steady-State Precession" (TrueFISP) MR angiography (MRA) for diagnosis of renal arterial stenosis (RAS) in hypertensive patients. METHODS: Twenty-two patients underwent both TrueFISP MRA and contrast-enhanced MRA (CE-MRA) on a 1.5-T MR imager. Volume of main renal arteries, length of maximal visible renal arteries, number of visualized branches, stenotic grade, and subjective quality were compared. Paired 2-tailed Student t test and Wilcoxon signed rank test were applied to evaluate the significance of these variables. RESULTS: Volume of main renal arteries, length of maximal visible renal arteries, and number of branches indicated no significant difference between the 2 techniques (P > 0.05). Stenotic degree of 10 RAS was greater on CE-MRA than on TrueFISP MRA. Qualitative scores from TrueFISP MRA were higher than those from CE-MRA (P < 0.05). CONCLUSIONS: TrueFISP MRA is a reliable and accurate method for evaluating RAS.

Etanercept ameliorates inflammation and pain in a novel mono-arthritic multi-flare model of streptococcal cell wall induced arthritis.

BACKGROUND: The impact of anti-TNF, corticosteroid and analgesic therapy on inflammation and pain was evaluated in a novel mono-arthritic multi-flare rat Streptococcal Cell Wall (SCW) model using Etanercept, Dexamethasone and Buprenorphine. METHODS: Multiple flares of arthritis were induced with an intra-articular injection of SCW in the hind ankle on day 1, followed by intravenous challenges on days 21 and 42. Inflammation and pain were monitored in the hind paws. Cytokine profiling, cell phenotyping, bioluminescence imaging and histopathological evaluation were also performed. RESULTS: Local injection of SCW caused a rapid onset of inflammation and pain in the injected ankle which resolved within 4 days (Flare 1). Intravenous injection 20 days after sensitization resulted in an increase in ankle diameter and pain, which partially resolved in 8 days (Flare 2). The subsequent intra-venous injection in the same animals 14 days after resulted in a more chronic disease with inflammation and pain persisting over a period of 10 days (Flare 3). In Flare 2, therapeutic administration of Dexamethasone inhibited paw swelling (95%; P<0.001) and pain (55%; P<0.05). Therapeutic administration of Buprenorphine inhibited pain (80%; P<0.001) without affecting paw swelling (0%). Prophylactic administration of Etanercept in Flare 2 inhibited paw swelling (≥60%; P<0.001) and pain by ≥30%. Expression of IL-1ß, IL-6, MCP-1 and CINC was reduced by >50% (P<0.001). Treatment with Etanercept in Flare 3 inhibited paw swelling by 60% (P<0.001) and pain by 25%. Prior treatment with Etanercept in Flare 2 followed by re-administration in Flare 3 led to a complete loss in the efficacy of Etanercept. Systemic exposure of Etanercept corroborated with lack of efficacy. Dexamethasone inhibited inflammation and pain in both Flares 2 and 3 (P<0.001). CONCLUSIONS: We established a novel multi-flare SCW arthritis model enabling drug intervention in different stages of disease. We show for the first time the evaluation of inflammation and pain simultaneously in this model. Etanercept and Dexamethasone inhibited inflammation, pain and proinflammatory cytokines in this model. Taken together, this model facilitates the assessment of anti-rheumatic agents targeting inflammation and pain in the multiple flare paradigm and offers a powerful tool for drug discovery.

The value of oral contrast-enhanced gastric ultrasonography in the diagnosis and staging of benign peptic ulcer.

We evaluate the value of oral contrast-enhanced gastric ultrasonography (OCUS) by comparing it with conventional gastroscopy in diagnosing and staging benign peptic ulcer. From July 2018 to December 2020, 44 patients with gastroscopy-confirmed benign peptic ulcers (a total of 45 ulcers were detected), who also received OCUS, were retrospectively reviewed. Each patient's ultrasound images were compared with gastroscopy and pathology findings. The characteristics of ultrasonic images of different stages of ulcer were analysed. A total of 43 ulcers were detected by OCUS in 44 patients with benign peptic ulcers. There were no false positive results among the OCUS exams, but two ulcers were misdiagnosed. OCUS for benign peptic ulcer staging also shows acceptable clinical practice results. OCUS is useful for detecting and staging benign peptic ulcer, and may be considered an alternative method for conventional gastroscopy. OCUS is especially useful in the follow-up of BPU treatment, but futher study is needed to improve the diagnostic accuracy of benign and malignant ulcers.

Multimodal Imaging Reveals that Sustained Inhibition of HIF-Prolyl Hydroxylases Induces Opposing Effects on Right and Left Ventricular Function in Healthy Rats.

PURPOSE: Hypoxia-inducible factor (HIF) drives transcription of critical hypoxia response genes, increasing the production of red blood cells in low oxygen conditions. In the absence of hypoxia, HIF is degraded by prolyl hydroxylases (HIF-PHs). Pharmacological HIF-PH inhibition stabilizes HIF and is being studied as a treatment for anemia. However, like sustained hypoxia, HIF-PH inhibition may increase pulmonary arterial pressure leading to right ventricular hypertrophy. The aim of this study was to assess the cardiac effects of sustained pharmacological HIF-PH inhibition using multimodal imaging, blood analysis, and histology. METHODS: Rats were dosed daily with a pan HIF-PH inhibitor or vehicle for 4 weeks followed by a 2-week washout period and underwent longitudinal magnetic resonance imaging (MRI) and echocardiography to simultaneously assess RV and LV function. Blood samples from weeks four and six were analyzed to determine red blood cell composition. Histology was performed on the cardiac tissue from a subset of rats at weeks four and six to assess structural effects. RESULTS: Imaging revealed that RV ejection fraction was reduced in animals receiving HIF-PH inhibitor and resulted in RV hypertrophy. Interestingly, HIF-PH inhibition had the opposite effect on the left ventricle (LV), increasing contractility measured by LV ejection fraction. LV effects were reversed by week six, while RV effects (functional and structural) were sustained. CONCLUSION: These opposing cardiac effects of HIF-PH inhibition warrant further study to both understand the potential negative effects on RV structure and function and investigate the therapeutic potential of increased LV contractility for conditions like heart failure.

Unveiling Organic Electrode Materials in Aqueous Zinc-Ion Batteries: From Structural Design to Electrochemical Performance.

Aqueous zinc-ion batteries (AZIBs) are one of the most compelling alternatives of lithium-ion batteries due to their inherent safety and economics viability. In response to the growing demand for green and sustainable energy storage solutions, organic electrodes with the scalability from inexpensive starting materials and potential for biodegradation after use have become a prominent choice for AZIBs. Despite gratifying progresses of organic molecules with electrochemical performance in AZIBs, the research is still in infancy and hampered by certain issues due to the underlying complex electrochemistry. Strategies for designing organic electrode materials for AZIBs with high specific capacity and long cycling life are discussed in detail in this review. Specifically, we put emphasis on the unique electrochemistry of different redox-active structures to provide in-depth understanding of their working mechanisms. In addition, we highlight the importance of molecular size/dimension regarding their profound impact on electrochemical performances. Finally, challenges and perspectives are discussed from the developing point of view for future AZIBs. We hope to provide a valuable evaluation on organic electrode materials for AZIBs in our context and give inspiration for the rational design of high-performance AZIBs.

Electropolymerization of Donor-Acceptor Conjugated Polymer for Efficient Dual-Ion Storage.

Rationally designed organic redox-active materials have attracted numerous interests due to their excellent electrochemical performance and reasonable sustainability. However, they often suffer from poor cycling stability, intrinsic low operating potential, and poor rate performance. Herein, a novel Donor-Acceptor (D-A) bipolar polymer with n-type pyrene-4,5,9,10-tetraone unit storing Li cations and p-type carbazole unit which attracts anions and provides polymerization sites is employed as a cathode for lithium-ion batteries through in situ electropolymerization. The multiple redox reactions and boosted kinetics by the D-A structure lead to excellent electrochemical performance of a high discharge capacity of 202 mA h g-1 at 200 mA g-1, impressive working potential (2.87 and 4.15 V), an outstanding rate capability of 119 mA h g-1 at 10 A g-1 and a noteworthy energy density up to 554 Wh kg-1. This strategy has significant implications for the molecule design of bipolar organic cathode for high cycling stability and high energy density.

Interbody Fusion Cage Design Driven by Topology Optimization.

OBJECTIVE: We used topology optimization technology to explore the new theory and method of interbody fusion cage design and realized an innovative design of interbody cages. METHODS: The lumbar spine of a normal healthy volunteer was scanned to perform reverse modeling. Based on the scan data for the L1-L2 segments of the lumbar spine, a three dimensional model was reconstructed to obtain the complete simulation model of the L1-L2 segment. The boundary inversion method was used to obtain approximately isotropic material parameters that can effectively characterize the mechanical behavior of vertebrae, thereby reducing the computational complexity. The topology description function was used to model the clinically used traditional fusion cage to obtain Cage A. The moving morphable void-based topology optimization method was used for the integrated design of size, shape, and topology to obtain the optimized fusion cage, Cage B. RESULTS: The volume fraction of the bone graft window in Cage B was 74.02%, which was 60.67% higher than that (46.07%) in Cage A. Additionally, the structural strain energy in the design domain of Cage B was 1.48 mJ, which was lower than that of Cage A (satisfying the constraints). The maximum stress in the design domain of Cage B was 5.336 Mpa, which was 35.6% lower than that (8.286 Mpa) of Cage A. In addition, the surface stress distribution of Cage B was more uniform than that of Cage A. CONCLUSIONS: This study proposed a new innovative design method for interbody fusion cages, which not only provides new insights into the innovative design of interbody fusion cages but may also guide the customized design of interbody fusion cages in different pathological environments.

Differential analysis of transcriptomic and metabolomic of free fatty acid rancidity process in oil palm (Elaeis guineensis) fruits of different husk types.

Introduction: Oil palm is the world's highest yielding oil crop and its palm oil has high nutritional value, making it an oilseed plant with important economic value and application prospects. After picking, oil palm fruits exposed to air will gradually become soft and accelerate the process of fatty acid rancidity, which will not only affect their flavor and nutritional value, but also produce substances harmful to the human body. As a result, studying the dynamic change pattern of free fatty acids and important fatty acid metabolism-related regulatory genes during oil palm fatty acid rancidity can provide a theoretical basis for improving palm oil quality and extending its shelf life. Methods: The fruit of two shell types of oil palm, Pisifera (MP) and Tenera (MT), were used to study the changes of fruit souring at different times points of postharvesting, combined with LC-MS/MS metabolomics and RNA-seq transcriptomics techniques to analyze the dynamic changes of free fatty acids during fruit rancidity, and to find out the key enzyme genes and proteins in the process of free fatty acid synthesis and degradation according to metabolic pathways. Results and discussion: Metabolomic study revealed that there were 9 different types of free fatty acids at 0 hours of postharvest, 12 different types of free fatty acids at 24 hours of postharvest, and 8 different types of free fatty acids at 36 hours of postharvest. Transcriptomic research revealed substantial changes in gene expression between the three harvest phases of MT and MP. Combined metabolomics and transcriptomics analysis results show that the expression of SDR, FATA, FATB and MFP four key enzyme genes and enzyme proteins in the rancidity of free fatty acids are significantly correlated with Palmitic acid, Stearic acid, Myristic acid and Palmitoleic acid in oil palm fruit. In terms of binding gene expression, the expression of FATA gene and MFP protein in MT and MP was consistent, and both were expressed higher in MP. FATB fluctuates unevenly in MT and MP, with the level of expression growing steadily in MT and decreasing in MP before increasing. The amount of SDR gene expression varies in opposite directions in both shell types. The above findings suggest that these four enzyme genes and enzyme proteins may play an important role in regulating fatty acid rancidity and are the key enzyme genes and enzyme proteins that cause differences in fatty acid rancidity between MT and MP and other fruit shell types. Additionally, differential metabolite and differentially expressed genes were present in the three postharvest times of MT and MP fruits, with the difference occurring 24 hours postharvest being the most notable. As a result, 24 hours postharvest revealed the most obvious difference in fatty acid tranquility between MT and MP shell types of oil palm. The results from this study offer a theoretical underpinning for the gene mining of fatty acid rancidity of various oil palm fruit shell types and the enhancement of oilseed palm acid-resistant germplasm cultivation using molecular biology methods.

A Randomized Phase III Study of Anlotinib Versus Bevacizumab in Combination With CAPEOX as First-Line Therapy for RAS/BRAF Wild-Type Metastatic Colorectal Cancer: A Clinical Trial Protocol.

Background: Chemotherapy combined with antivascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor monoclonal antibodies is the most promising approach to prolong survival and improve the quality of life of patients with unresectable metastatic colorectal cancer (mCRC). Anlotinib is an oral antiangiogenic tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors a/ß. Since anlotinib combined with oxaliplatin and capecitabine (CAPEOX) as a first-line treatment was previously shown to be effective and safe for patients with RAS/BRAF wild-type (WT) mCRC, we designed this randomized, open-label, parallel-group, non-inferiority, phase III study to evaluate the efficacy and safety of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX in patients with RAS/BRAF WT mCRC. Methods/design: The primary inclusion criteria are Eastern Cooperative Oncology Group performance status 0/1, confirmed RAS/BRAF WT colorectal adenocarcinoma, and unresectable metastases assessed by a multidisciplinary team. The main exclusion criteria are as follows: high microsatellite instability or deficient mismatch repair status, resectable or potentially resectable metastases, and previous systemic therapy for mCRC. A total of 698 patients will be randomized into the anlotinib and bevacizumab groups in a 1:1 ratio. Patients will receive 4 to 8 cycles of induction therapy (CAPEOX plus anlotinib or bevacizumab), followed by maintenance treatment (capecitabine plus anlotinib or bevacizumab) until disease progression or unacceptable toxicity. Progression-free survival (PFS) assessed by an independent review committee is the primary endpoint, whereas investigator-assessed PFS, overall survival, objective response rate, disease control rate, duration of response, resection rate of liver metastases, quality of life, and safety are the secondary endpoints. Enrollment commenced in May 2021. Discussion: A prospective, randomized, phase III trial will provide a meaningful comparison of the efficacy and safety of anlotinib plus CAPEOX with standard treatment for patients with unresectable RAS/BRAF WT mCRC.