Ki-67 index as a predictive marker of meningioma recurrence following surgical resection.

BACKGROUND: Meningiomas are the most common primary intracranial tumors in adults. Although benign in a majority of cases, they have a variable clinical course and may recur even after a thorough surgical resection. Ki-67, a nuclear protein involved in cell cycle regulation, has been widely studied as a marker of cellular proliferation in various cancers. However, the prognostic significance of Ki-67 in meningiomas remains controversial. Here, we investigate the Ki-67 index, as a predictive marker of meningioma recurrence following surgical resection and compare it to established prognostic markers such as WHO grade and degree of resection. METHODS: The medical records of 451 patients with previously untreated cranial meningiomas who underwent resections from January 2011 to January 2021 at North Shore University Hospital (NSUH) were reviewed. Collected data included WHO grade, Ki-67 proliferative index, degree of resection - gross (GTR) vs subtotal (STR) - as judged by the surgeon, tumor location, and meningioma recurrence. This study was approved by the NSUH Institutional Review Board IRB 21-1107. RESULTS: There were 290 patients with grade I, 154 with grade II, and 7 with grade III meningiomas. The average post-resection follow-up period was 4 years, and 82 tumors (18 %) recurred. Higher WHO grades were associated with higher rates of recurrence, with rates of 11.4 %, 27.9 %, and 71.4 % for grades 1, 2, and 3, respectively, and subtotal resection corresponded to a higher rate of recurrence than total resection (34.3 % and 13.4 %, respectively). Higher WHO grades also correlated with higher Ki-67 scores (2.59, 10.01, and 20.71) for grades 1, 2, and 3, respectively. A multivariate logistic regression model identified Ki-67 and degree of resection as independent predictive variables for meningioma recurrence, with Ki-67 specifically predicting recurrence in the WHO grade II subset when analyzed separately for WHO grades I and II. CONCLUSION: Our 10-year retrospective study suggests that the Ki-67 index is an important predictive marker for recurrence of intracranial meningiomas following surgical resection, particularly among patients with WHO grade II tumors. Our findings add to a growing body of data that support inclusion of Ki-67 index in the WHO grading criteria for patients with meningiomas.

Interfragmentary compression force and fixation stability of lateral tibial plateau fractures in normal and osteoporotic bones.

Lateral platform collapse in fixations of lateral tibial plateau fractures (TPFs) using either double-lag screws fixation (DSF) or locking-plate fixation (LPF) is not rare. This study aimed to explore the effect of enhancing the interfragmentary compression force (IFCF) on fixation stability in lateral TPFs in normal and osteoporotic bones using finite element analysis. Finite element models of DSF in normal bone and LPF in normal and osteoporotic bones were established to simulate the fixations of lateral TPF. After model validation, axial compressive forces of 500, 1000, 1500, and 2500 N to the tibial plateau along with an IFCF of 0, 100, 200, and 300 N were applied. The maximum axial micromotion of the lateral fragment (MAM-LF), maximal translational micromotion of the lateral fragment (MTM-LF), peak von Mises stress (VMS), and peak equivalent elastic strain of the lateral fragment (EES-LF) were evaluated. The MAM-LF showed a decreasing trend as the IFCF increased in all models. For DSF models, the peak VMS of implants increased as the IFCF increased when the axial loads were 500 and 1000 N. The peak EES-LF decreased as the IFCF increased under axial loads of 1000, 1500, and 2500 N. For the normal and osteoporotic LPF models, the peak VMS of the implants decreased as the IFCF increased. Peak EES-LF decreased as IFCF increased. In conclusion, enhancing IFCF was beneficial in improving the fixation stability of lateral TPF. The optimal IFCF for DSF and LPF should be as high as reasonably feasible.

Application of a combined cancellous lag screw enhances the stability of locking plate fixation of osteoporotic lateral tibial plateau fracture by providing interfragmentary compression force.

BACKGROUND: Insufficient interfragmentary compression force (IFCF) frequently leads to unstable fixation of osteoporotic lateral tibial plateau fractures (OLTPFs). A combined cancellous lag screw (CCLS) enhances IFCF; however, its effect on OLTPF fixation stability remains unclear. Therefore, we investigated the effect of CCLS on OLTPF stability using locking plate fixation (LPF). MATERIALS AND METHODS: Twelve synthetic osteoporotic tibial bones were used to simulate OLTPFs, which were fixed using LPF, LPF-AO cancellous lag screws (LPF-AOCLS), and LPF-CCLS. Subsequently, 10,000 cyclic loadings from 30 to 400 N were performed. The initial axial stiffness (IAS), maximal axial micromotion of the lateral fragment (MAM-LF) measured every 1000 cycles, and failure load after 10,000 cycles were tested. The same three fixations for OLTPF were simulated using finite element analysis (FEA). IFCFs of 0, 225, and 300 N were applied to the LPF, LPF-AOCLS, and LPF-CCLS, respectively, with a 1000-N axial compressive force. The MAM-LF, peak von Mises stress (VMS), peak equivalent elastic strain of the lateral fragment (EES-LF), and nodes of EES-LF > 2% (considered bone destruction) were calculated. RESULTS: Biomechanical tests revealed the LPF-AOCLS and LPF-CCLS groups to be superior to the LPF group in terms of the IAS, MAM-LF, and failure load (all p < 0.05). FEA revealed that the MAM-LF, peak VMS, peak EES-LF, and nodes with EES-LF > 2% in the LPF were higher than those in the LPF-AOCLS and LPF-CCLS. CONCLUSION: IFCF was shown to enhance the stability of OLTPFs using LPF. Considering overscrewing, CCLS is preferably recommended, although there were no significant differences between CCLS and AOCLS.

Influence of loneliness burden on cardio-cerebral vascular disease among the Chinese older adult: a national cohort study.

Background: Adverse psychosocial factors play an important role in cardio-cerebral vascular disease (CCVD). The aim of this study was to evaluate the impact of the cumulative burden of loneliness on the risk of CCVD in the Chinese older adult. Methods: A total of 6,181 Chinese older adult over the age of 62 in the monitoring survey of the fourth Sample Survey of the Aged Population in Urban and Rural China (SSAPUR) were included in this study. The loneliness cumulative burden (scored by cumulative degree) was weighted by the loneliness score for two consecutive years (2017-2018) and divided into low- and high-burden groups. The outcome was defined as the incidence of CCVD 1 year later (2018-2019). A multivariate logistic regression model was used to examine the relationship between the cumulative burden of loneliness and the new onset of CCVD. Results: Among participants, 18.9% had a higher cumulative burden of loneliness, and 11.5% had a CCVD incidence within 1 year. After multivariate adjustment, the risk of developing CCVD in the high-burden group was approximately 37% higher than that in the low-burden group (OR 1.373, 95%CI 1.096-1.721; p = 0.006). Similar results were obtained when calculating the burden based on cumulative time. Longitudinal change in loneliness was not significantly associated with an increased risk of CCVD. A higher cumulative burden of loneliness may predict a higher risk of developing CCVD in older adult individuals aged 62-72 years or in those with diabetes. Conclusion: The cumulative burden of loneliness can be used to assess the risk of new-onset CCVD in the older adult in the short term.

The retropharyngeal reduction plate for atlantoaxial dislocation: a finite element analysis.

Objective: To investigate the biomechanical properties of the retropharyngeal reduction plate by comparing the traditional posterior pedicle screw-rod fixation by finite element analysis. Methods: Two three-dimensional finite element digital models of the retropharyngeal reduction plate and posterior pedicle screw-rod fixation were constructed and validated based on the DICOM (Digital Imaging and Communications in Medicine) data from C1 to C4. The biomechanical finite element analysis values of two internal fixations were measured and calculated under different conditions, including flexion, extension, bending, and rotation. Results: In addition to the backward extension, there was no significant difference in the maximum von Mises stress between the retropharyngeal reduction plate and posterior pedicle screw fixation under other movement conditions. The retropharyngeal reduction plate has a more uniform distribution under different conditions, such as flexion, extension, bending, and rotation. The stress tolerance of the two internal fixations was basically consistent in flexion, extension, left bending, and right bending. Conclusion: The retropharyngeal reduction plate has a relatively good biomechanical stability without obvious stress concentration under different movement conditions. It shows potential as a fixation option for the treatment of atlantoaxial dislocation.

Detection of kinematic abnormalities in persons with knee osteoarthritis using markerless motion capture during functional movement screen and daily activities.

Background: The functional movement screen (FMS) has been used to identify deficiencies in neuromuscular capabilities and balance among athletes. However, its effectiveness in detecting movement anomalies within the population afflicted by knee osteoarthritis (KOA), particularly through the application of a family-oriented objective assessment technique, remains unexplored. The objective of this study is to investigate the sensitivity of the FMS and daily activities in identifying kinematic abnormalities in KOA people employing a markerless motion capture system. Methods: A total of 45 persons, presenting various Kellgren-Lawrence grades of KOA, along with 15 healthy controls, completed five tasks of the FMS (deep squat, hurdle step, and in-line lunge) and daily activities (walking and sit-to-stand), which were recorded using the markerless motion capture system. The kinematic waveforms and discrete parameters were subjected to comparative analysis. Results: Notably, the FMS exhibited greater sensitivity compared to daily activities, with knee flexion, trunk sagittal, and trunk frontal angles during in-line lunge emerging as the most responsive indicators. Conclusion: The knee flexion, trunk sagittal, and trunk frontal angles during in-line lunge assessed via the markerless motion capture technique hold promise as potential indicators for the objective assessment of KOA.

CF2-II Alternative Splicing Isoform Regulates the Expression of Xenobiotic Tolerance-Related Cytochrome P450 CYP6CY22 in Aphis gossypii Glover.

The expression of P450 genes is regulated by trans-regulatory factors or cis-regulatory elements and influences how endogenous or xenobiotic substances are metabolized in an organism's tissues. In this study, we showed that overexpression of the cytochrome P450 gene, CYP6CY22, led to resistance to cyantraniliprole in Aphis gossypii. The expression of CYP6CY22 increased in the midgut and remaining carcass of the CyR strain, and after repressing the expression of CYP6CY22, the mortality of cotton aphids increased 2.08-fold after exposure to cyantraniliprole. Drosophila ectopically expressing CYP6CY22 exhibited tolerance to cyantraniliprole and cross-tolerance to xanthotoxin, quercetin, 2-tridecanone, tannic acid, and nicotine. Moreover, transcription factor CF2-II (XM_027994540.2) is transcribed only as the splicing variant isoform CF2-II-AS, which was found to be 504 nucleotides shorter than CF2-II in A. gossypii. RNAi and yeast one-hybrid (Y1H) results indicated that CF2-II-AS positively regulates CYP6CY22 and binds to cis-acting element p (-851/-842) of CYP6CY22 to regulate its overexpression. The above results indicated that CYP6CY22 was regulated by the splicing isoform CF2-II-AS, which will help us further understand the mechanism of transcriptional adaption of cross-tolerance between synthetic insecticides and plant secondary metabolites mediated by P450s.

Identification of inducible CYP3 and CYP4 genes associated with abamectin tolerance in the fat body and Malpighian tubules of Spodoptera litura.

Abamectin, as a broad-spectrum bioinsecticide, has been widely used for the control of Lepidoptera insects, resulting in different levels of resistance to abamectin in Spodoptera litura. Cytochrome P450 monooxygenases (P450s) are known for their important roles in insecticide detoxification. In this study, the expression of SlCYP6B40, SlCYP4L12 and SlCYP9A32 in the fat body, and SlCYP4S9, SlCYP6AB12, SlCYP6AB58, SlCYP9A75a and SlCYP9A75b in Malpighian tubules was found to be significantly upregulated after abamectin exposure. SlCYP6AE44 and SlCYP6AN4 were simultaneously upregulated in these two tissues after abamectin exposure. Ectopically overexpressed SlCYP6AE44, SlCYP9A32 and SlCYP4S9 in transgenic Drosophila conferred tolerance to abamectin. In addition, homology modeling and molecular docking results suggested that SlCYP6AE44, SlCYP9A32 and SlCYP4S9 may be capable of binding with abamectin. These results demonstrate that upregulation of CYP3 and CYP4 genes may contribute to abamectin detoxification in S. litura and provide information for evidence-based insecticide resistance management strategies.

Nomogram for predicting venous thromboembolism after spinal surgery.

PURPOSE: This study aimed to establish a nomogram to predict the risk of venous thromboembolism (VTE), identifying potential risk factors, and providing theoretical basis for prevention of VTE after spinal surgery. METHODS: A retrospective analysis was conducted on 2754 patients who underwent spinal surgery. The general characteristics of the training group were initially screened using univariate logistic analysis, and the LASSO method was used for optimal prediction. Subsequently, multivariate logistic regression analysis was performed to identify independent risk factors for postoperative VTE in the training group, and a nomogram for predict risk of VTE was established. The discrimination, calibration, and clinical usefulness of the nomogram were separately evaluated using the C-index, receiver operating characteristic curve, calibration plot and clinical decision curve, and was validated using data from the validation group finally. RESULTS: Multivariate logistic regression analysis identified 10 independent risk factors for VTE after spinal surgery. A nomogram was established based on these independent risk factors. The C-index for the training and validation groups indicating high accuracy and stability of the model. The area under the receiver operating characteristic curve indicating excellent discrimination ability; the calibration curves showed outstanding calibration for both the training and validation groups. Decision curve analysis showed the clinical net benefit of using the nomogram could be maximized in the probability threshold range of 0.01-1. CONCLUSION: Patients undergoing spinal surgery with elevated D-dimer levels, prolonger surgical, and cervical surgery have higher risk of VTE. The nomogram can provide a theoretical basis for clinicians to prevent VTE.

A novel combined technology for treating hypertrophic scars: adipose tissue extract combined with fractional CO2 laser.

Introduction: Owing to the need for liposuction and its unsuitability for allogeneic transplantation, the clinical application of stromal vascular fraction gel (SVF-gel) combined with fractional CO2 laser for scar treatment is limited. Adipose tissue extract (ATE), rich in cytokines and growth factors, offers a more convenient option for clinical practice as it can be easily prepared using purely physical methods and has low immunogenicity. We aimed to evaluate the effectiveness of ATE combined with fractional CO2 laser in the treatment of hypertrophic scars. Methods: ATE was prepared using discarded liposuction fluid from patients undergoing liposuction. A rabbit ear hypertrophic scar model was established and treated with ATE, fractional CO2 laser, or a combination. PBS was used as a control. The scar appearance and histological changes were observed. The immunohistochemistry method was used to evaluate the expression of α-SMA, while perilipin was detected using immunofluorescence. Additionally, the level of adipogenic signal C/EBPα and PPARγ mRNA was studied. Results: Following treatment, the volume of hypertrophic scar decreased, resulting in a softer texture and thinner dermis. Additionally, there was a decrease in the infiltration of inflammatory cells, and the collagen arrangement became looser and more regular, and the expression of α-SMA also decreased, with the combination of ATE and fractional laser showing the most significant improvement. Moreover, the combination group was found to promote subcutaneous fat regeneration and increase the expression of adipogenic signals C/EBPα and PPARγ. Conclusion: The combination of ATE and fractional CO2 laser treatment has been shown to inhibit the development of hypertrophic scars. This effect may be attributed to the enhancement of adipogenesis and decrease in collagen deposition.

Biomechanical evaluation of different posterior fixation techniques for treating thoracolumbar burst fractures of osteoporosis old patients: a finite element analysis.

Objective: To investigate the biomechanical characteristics of different posterior fixation techniques in treatment of osteoporotic thoracolumbar burst fractures by finite element analysis. Methods: The Dicom format images of T10-L5 segments were obtained from CT scanning of a volunteer, and transferred to the Geomagic Studio software, which was used to build digital models. L1 osteoporotic burst fracture and different posterior fixation techniques were simulated by SolidWorks software. The data of ROM, the maximum displacement of fixed segment, ROM of fractured L1 vertebrae, the stress on the screws and rods as well as on fractured L1 vertebrae under different movement conditions were collected and analysed by finite element analysis. Results: Among the four groups, the largest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae occurred in CBT, and the corresponding data was 1.3°, 2.57 mm and 1.37°, respectively. While the smallest ROM of fixed segment, the maximum displacement of fixed segment and ROM of fractured vertebrae was found in LSPS, and the corresponding data was 0.92°, 2.46 mm and 0.89°, respectively. The largest stress of screws was 390.97 Mpa, appeared in CBT, and the largest stress of rods was 84.68 MPa, appeared in LSPS. The stress concentrated at the junction area between the root screws and rods. The maximum stress on fractured vertebrae was 93.25 MPa, appeared in CBT and the minimum stress was 56.68 MPa, appeared in CAPS. And the stress of fractured vertebrae concentrated in the middle and posterior column of the fixed segment, especially in the posterior edge of the superior endplate. Conclusion: In this study, long-segment posterior fixation (LSPF) provided with the greatest stability of fixed segment after fixation, while cortical bone screw fixation (CBT) provided with the smallest stability. Cement-augmented pedicle screw-rod fixation (CAPS) and combined using cortical bone screw and pedicle screw fixation (CBT-PS) provided with the moderate stability. CBT-PS exhibited superiority in resistance of rotational torsion for using multiple connecting rods. CAPS and CBT-PS maybe biomechanically superior options for the surgical treatment of burst TL fractures in osteoporotic patients.

The biomechanical effects of insoles with different cushioning on the knee joints of people with different body mass index grades.

Background: Enhancing knee protection for individuals who are overweight and obese is crucial. Cushioning insoles may improve knee biomechanics and play a significant protective role. However, the impact of insoles with varying cushioning properties on knee joints in individuals with different body mass index (BMI) categories remains unknown. Our aim was to investigate the biomechanical effects of insoles with different cushioning properties on knee joints across different BMI grades. Methods: Gravity-driven impact tests were used to characterize the cushioning properties of three types of Artificial Cartilage Foam (ACF18, 28, and 38) and ethylene-vinyl acetate (EVA) insoles. Knee joint sagittal, coronal, and vertical axis angles and moments were collected from healthy-weight (BMI 18.5-23.9 kg/m2, n = 15), overweight (BMI 24.0-27.9 kg/m2, n = 16), and obese (BMI ≥28.0 kg/m2, n = 15) individuals randomly assigned four different insoles during a drop jump. The Kruskal-Wallis test and mixed model repeated measures analysis of variance were used to compare differences among cushioning and biomechanical data across various insoles, respectively. Results: ACF showed higher cushioning than EVA, and ACF38 was the highest among the three types of ACF (all p < 0.001). During the drop jump, the knee flexion angles and moments of the ACF insoles were lower than those of the EVA insoles, the knee adduction angles of the ACF18 and ACF28 insoles were lower than those of the EVA insoles, and ACF18 insoles increased the first cushion time (all p < 0.05) for all participants in whom biomechanical variables demonstrated no interactions between insoles and BMI. Regarding the BMI-dependent biomechanical variables, compared with the EVA insoles, ACF28 insoles decreased the knee flexion angle and ACF38 insoles decreased the knee adduction and rotation moment in the healthy-weight group; ACF18 insoles decreased the knee flexion angle and ACF38 insoles decreased the knee moment in the overweight group; ACF28 insoles decreased the knee flexion and adduction moment, and ACF38 insoles decreased the knee flexion angle and rotation moment in the obese group (all p < 0.05). Conclusion: Insoles with higher cushioning properties could improve knee biomechanics and provide better knee joint protection in people across different BMI ranges.

Adrenal SGLT1 or SGLT2 as predictors of atherosclerosis under chronic stress based on a computer algorithm.

Background: Chronic stress promotes the development of atherosclerosis, causing disruptions in the body's hormone levels and changes in the structural function of organs. Objective: The purpose of this study was to investigate the pathological changes in the adrenal gland in a model of atherosclerosis under chronic stress and to verify the expression levels of Sodium-glucose cotransporter (SGLT) 1 and SGLT2 in the adrenal gland and their significance in the changes of adrenal gland. Methods: The model mice were constructed by chronic unpredictable stress, high-fat diet, and Apoe-/- knockout, and they were tested behaviorally at 0, 4, 8 and 12 weeks. The state of the abdominal artery was examined by ultrasound, and the pathological changes of the aorta and adrenal glands were observed by histological methods, and the expression levels and distribution of SGLT1 and SGLT2 in the adrenal gland were observed and analyzed by immunofluorescence and immunohistochemistry. The predictive value of SGLT1 and SGLT2 expression levels on intima-media thickness, internal diameter and adrenal abnormalities were verified by receiver operating characteristic (ROC) curves, support vector machine (SVM) and back-propagation (BP) neural network. Results: The results showed that chronic stress mice had elevated expression levels of SGLT1 and SGLT2. The model mice developed thickening intima-media and smaller internal diameter in the aorta, and edema, reticular fiber rupture, increased adrenal glycogen content in the adrenal glands. More importantly, analysis of ROC, SVM and BP showed that SGLT1 and SGLT2 expression levels in the adrenal glands could predict the above changes in the aorta and were also sensitive and specific predictors of adrenal abnormalities. Conclusion: SGLT1 and SGLT2 could be potential biomarkers of adrenal injury in atherosclerosis under chronic stress.

The C2H2 zinc finger transcription factor CF2-II regulates multi-insecticide resistance-related gut-predominant ABC transporters in Aphis gossypii Glover.

Clarifying the molecular mechanisms of cotton aphid resistance to various insecticides is crucial for the long-term safe application of insecticides in chemical control. ATP-binding cassette (ABC) transporters mediate the membrane transport of various substrates (including exogenous substances). Experiments confirmed that ABCB5, ABCF2, and MRP12 contributed to high levels of resistance to spirotetramat, cyantraniliprole, thiamethoxam or imidacloprid. Binding sites of the C2H2 zinc finger transcription factor CF2-II was predicted to be located in the promoters of ABCB5, ABCF2, and MRP12. The expression levels of ABCB5, ABCF2, and MRP12 were significantly upregulated after silencing CF2-II. The results of dual-luciferase reporter assays demonstrated a negative regulatory relationship between CF2-II and ABC transporter promoters. Furthermore, yeast one-hybrid (Y1H) and electrophoresis mobility shift assays (EMSAs) revealed that CF2-II inhibited the expression of ABC transporter genes through interaction with binding sites [ABCF2.p (-1149/-1140) or MRP12.p (-1189/-1181)]. The above results indicated that ABCB5, ABCF2, and MRP12 were negatively regulated by the transcription factor CF2-II, which will help us further understand the mechanism of transcriptional adaption of multi-insecticides resistant related ABC transporters in response to xenobiotics.

A masked gene concealed hand in glove in the forkhead protein crocodile regulates the predominant detoxification CYP6DA1 in Aphis gossypii Glover.

Cytochrome P450-mediated metabolism is an important mechanism of insecticide resistance, most studies show upregulated transcript levels of P450s in resistant insect strains. Our previous studies illustrated that some upregulated P450s were associated with cyantraniliprole resistance, and it is more comprehensive to use the tissue specificity of transcriptomes to compare resistant (CyR) and susceptible (SS) strains. In this study, the expression profiles of P450s in a CyR strain compared with a SS strain in remaining carcass or midgut were investigated by RNA sequencing, and candidate genes were selected for functional study. Drosophila melanogaster bioassays suggested that ectopic overexpression of CYP4CK1, CYP6CY5, CYP6CY9, CYP6CY19, CYP6CZ1 and CYP6DA1 in flies was sufficient to confer cyantraniliprole resistance, among which CYP6DA1 was the predominant contributor to resistance (12.24-fold). RNAi suppression of CYP4CK1, CYP6CY5, CYP6CY9 and CYP6DA1 significantly increased CyR aphid sensitivity to cyantraniliprole. The CYP6DA1 promoter had two predicted binding sites for crocodile (CROC), an intron-free ORF with bidirectional transcription yielding CROC (+) and CROC (-). Y1H, RNAi and EMSA found that CROC (-) was a transcription factor directly regulating CYP6DA1 expression. In conclusion, P450 genes contribute to cyantraniliprole resistance, and the transcription factor CROC (-) regulates the expression of CYP6DA1 in A. gossypii.

Inducible Cytochrome P450s in the Fat Body and Malpighian Tubules of the Polyphagous Pests of Spodoptera litura Confer Xenobiotic Tolerance.

Cytochrome P450 plays vital roles in detoxifying xenobiotics. In this study, SlCYP340A and SlCYP340L expression in the Spodoptera litura fat body and SlCYP332A1, SlCYP6AB12, SlCYP6AB58, SlCYP6AB59, and SlCYP6AN4 expression in the Malpighian tubules were significantly upregulated after cyantraniliprole exposure, and SlCYP6AB58 and SlCYP6AB59 expression levels were simultaneously increased in the Malpighian tubules after gossypol treatment. Drosophila ectopically expressing candidate P450 genes showed that SlCYP332A1, SlCYP6AB12, SlCYP6AB59, SlCYP6AN4, and SlCYP340A conferred cyantraniliprole tolerance. The overexpression of SlCYP6AB58 and SlCYP6AB59 in Drosophila increased the number of eggs laid under the gossypol treatment. Moreover, the knockdown of SlCYP332A1, SlCYP6AB12, SlCYP6AB59, SlCYP6AN4, and SlCYP340A increased S. litura mortality under the cyantraniliprole treatment. Homology modeling and molecular docking results suggested that candidate P450 has the potential to bind with cyantraniliprole. These results indicate that the CYP3 and CYP4 genes participate in cyantraniliprole detoxification and that SlCYP6AB59 may be simultaneously involved in the gossypol tolerance of S. litura.

Development of a continuously perfused ex vivo kidney training model for laparoscopic partial nephrectomy: validity and efficiency.

BACKGROUND: Suture hemostasis is essential for laparoscopic partial nephrectomy (LPN). This study aimed to develop, validate, and test the efficacy of a continuously perfused training model (CPTM) in LPN with high-level simulated bleeding. MATERIALS AND METHODS: The CPTM was constructed using fresh porcine kidneys with renal arteries continuously perfused with red-dyed liquid gelatin. Twenty-nine participants with expert, intermediate, or novice laparoscopic experience levels were recruited. The expert and intermediate participants evaluated the CPTM, and the novice participants were randomly assigned to one of two groups to complete training on a CPTM or dry box training model (DBTM). Messick's framework criteria were utilized to assess the validity and training efficacy of the model. The data were analyzed using the Mann-Whitney U , Kruskal-Wallis, and Friedman tests. A value of P< 0.05 was considered statistically significant. RESULTS: Positive comments were provided by all experts and intermediates for the Content . The Relationships with other variables demonstrated significant differences among novices, intermediates, and experts in all metrics ( P< 0.05). The Consequences showed that the CPTM helped novices acquire LPN skills. The training efficacy was significantly better than that of the DBTM ( P< 0.05). There were no significant differences between the final performances of the novices and the initial performances of the experts ( P >0.05). Synthesizing all metrics, the LPN skills learned using CPTMs were significantly improved in the 12th round of training. CONCLUSION: The CPTM offered a high-level simulation of bleeding with realistic tissue texture for acquiring LPN skills. Training of no fewer than 12 rounds is recommended for a novice's LPN training on the CPTM.

Restoration of CPT1A-mediated fatty acid oxidation in mesothelial cells protects against peritoneal fibrosis.

Background: Peritoneal dialysis (PD) is limited by gradual fibrotic remodeling in the peritoneum, a process involving profibrotic response of mesothelial cells. However, the role of fatty acid oxidation (FAO) and carnitine palmitoyltransferase 1A (CPT1A) in this process remains unexplored. Methods: FAO and CPT1A expression were characterized in mesothelial cells from patients on long-term PD and from a mouse model of PD using multiple experimental methods, including single-cell sequencing, seahorse assay, real-time quantitative PCR, Western blot, and immunofluorescence staining. Overexpression of CPT1A was achieved in a human mesothelial cell line and in primary mouse mesothelial cells. Finally, genetic and pharmacological manipulations of CPT1A were performed in a mouse model of PD. Results: Herein, FAO and CPT1A expression were reduced in mesothelial cells from patients on long-term PD, which negatively correlated with expression of fibrogenic markers in these cells. This was corroborated in PD mice, as well as in mouse and human mesothelial cells incubated with transforming growth factor (TGF) ß1. CPT1A overexpression in mesothelial cells, which prevented TGFß1-induced suppression of mitochondrial respiration, restored cellular ATP levels and downregulated the expression of fibrogenic markers. Furthermore, restoration of FAO by overexpressing CPT1A in PD mice reversed profibrotic phenotype in mesothelial cells and reduced fibrotic lesions in the peritoneum. Treatment with the CPT1A activator C75 induced similar therapeutic benefit in PD mice. In contrast, inhibition of FAO with a CPT1 inhibitor caused more severe fibrosis in PD mice. Conclusions: A defective FAO is responsible for the profibrotic response of mesothelial cells and thus the peritoneal fibrogenesis. This aberrant metabolic state could be improved by modulating CPT1A in mesothelial cells, suggesting FAO enhancement in mesothelial cells is a potential treatment of peritoneal fibrosis.