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Abstract Recent advances in the genomics of glioblastoma (GBM) led to the introduction of molecular neuropathology but failed to translate into treatment improvement. This is largely attributed to the genetic and phenotypic heterogeneity of GBM, which are considered the major obstacle to GBM therapy. Here, we use advanced human GBM-like organoid (LEGO: Laboratory Engineered Glioblastoma-like Organoid) models and provide an unprecedented comprehensive characterization of LEGO models using single-cell transcriptome, DNA methylome, metabolome, lipidome, proteome, and phospho-proteome analysis. We discovered that genetic heterogeneity dictates functional heterogeneity across molecular layers and demonstrates that NF1 mutation drives mesenchymal signature. Most importantly, we found that glycerol lipid reprogramming is a hallmark of GBM, and several targets and drugs were discovered along this line. We also provide a genotype-based drug reference map using LEGO-based drug screen. This study provides new human GBM models and a research path toward effective GBM therapy.

In order to investigate the acoustic emission (AE) features of rocks in different (medium and strong) rockburst areas, the Sangzhuling Railway Tunnel granite in China was taken as an example, the mineral composition of rocks in different rockburst areas was analyzed by using XRD (X-ray diffraction) method. The Original rock cores of different rockburst areas were processed into standard rock specimens (diameter 50 mm, height 100 mm) in different directions (transverse, oblique and longitudinal). AE feature parameters (event number, ringing count and energy) of standard rock specimens during indoor uniaxial compression test were obtained by using AE technique. The variation law of AE feature parameters of rocks in different rockburst grade areas was then analyzed. The AE features of failure precursor of rocks in different rockburst areas were therefore discussed. It shows that compared with rocks in medium rockburst area, the content of quartz and feldspar of rocks in strong rockburst area is high, while the content of biotite is low; the rock in the strong rock burst area released more energy during the failure process with about 2–3 times that of the rock in the medium rock burst area; the cumulative ringing curve of rock in medium burst area is a stepped type, while the cumulative ringing curve of rock in strong burst area is the smoothed type; the end of the second and first AE quiet period may be regarded as the failure precursor of rocks in medium and strong rockburst area, respectively. The results presented herein are important for understanding the mechanisms of rockburst.

Abstract Background Cement-augmentation pedicle screws have been widely used in spinal internal fixation surgery combined with osteoporosis in recent years, which can significantly improve the fixation strength, but compared with conventional methods, whether it has more advantages is still inconclusive of evidencebased medicine. To systematically evaluate the efficacy and safety of cement-augmented pedicle screw in the treatment of thoracolumbar degenerative diseases with osteoporosis. Methods We searched PubMed, Embase, and Cochrane Library for studies published from the establishment of the database up until June 2023. We included studies that concerning the cement-augmented pedicle screw and the traditional pedicle screw placement for thoracolumbar degenerative diseases with osteoporosis. We excluded repeated publication, researches without full text, incomplete information or inability to conduct data extraction and animal experiments, case report, reviews and systematic reviews. STATA 15.1 software was used to analyze the data. Results A total of 12 studies were included in this meta-analysis. The sample size of patients were totally 881, of which, 492 patients in cement-augmented screw group and 389 patients in conventional screw group. Meta-analysis results showed that Japanese Orthopaedic Association (JOA) score (WMD = 1.69, 95% CI 1.15 to 2.22), intervertebral space height (WMD = 1.66, 95% CI 1.03 to 2.29) and post-operation fusion rate (OR = 2.80, 95% CI 1.49 to 5.25) were higher in the cement-augmented screw group than those in the conventional screw group. Operation time was longer in the cement-augmented screw group than that in the conventional screw group (WMD = 15.47, 95% CI 1.25 to 29.70). Screw loosening rate was lower in the cement-augmented screw group than those in the conventional screw group (OR = 0.13, 95% CI 0.07 to 0.22). However, hospitalization time, intraoperative blood loss and Visual analog scale (VAS) score were not significantly different between the two groups (P > 0.05). Conclusion Compared with conventional pedicle screw placement, cement-augmented pedicle screw is more effective in the treatment of osteoporotic thoracolumbar degenerative disease by improving fusion rate and interbody height, reducing the incidence of screw loosening, and elevating long-term efficacy.

Abstract The cytidine deaminase, Apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B, herein termed A3B), is a critical mutation driver that induces genomic instability in cancer by catalyzing cytosine-to-thymine (C-to-T) conversion and promoting replication stress (RS). However, the detailed function of A3B in RS is not fully determined and it is not known whether the mechanism of A3B action can be exploited for cancer therapy. Here, we conducted an immunoprecipitation-mass spectrometry (IP-MS) study and identified A3B to be a novel binding component of R-loops, which are RNA:DNA hybrid structures. Mechanistically, overexpression of A3B exacerbated RS by promoting R-loop formation and altering the distribution of R-loops in the genome. This was rescued by the R-loop gatekeeper, Ribonuclease H1 (RNASEH1, herein termed RNH1). In addition, a high level of A3B conferred sensitivity to ATR/Chk1 inhibitors (ATRi/Chk1i) in melanoma cells, which was dependent on R-loop status. Together, our results provide novel insights into the mechanistic link between A3B and R-loops in the promotion of RS in cancer. This will inform the development of markers to predict the response of patients to ATRi/Chk1i.

Pedunculoside, a triterpene saponin derived from various Ilex species, holds potential as a treatment for cardiovascular diseases. However, its clinical application is hindered by poor bioavailability, rapid elimination, and extensive intestinal metabolism to rotundic acid. To address these issues, a water-soluble inclusion complex of pedunculoside, namely, the beta-CD polymer inclusion complex of pedunculoside (pedunculoside–βCDP), was prepared in this study, and a comparative in vitro stability and pharmacokinetic behavior study was performed between pedunculoside and pedunculoside–βCDP. Both pedunculoside and pedunculoside–βCDP exhibited the highest stability in simulated gastric fluid and simulated intestinal fluid but were readily metabolized when co-incubated with Bifidobacterium adolescentis and Bifidobacterium breve. An LC-MS/MS analytical method for the simultaneous determination of pedunculoside and rotundic acid in rat plasma was successfully established, validated, and applied to investigate the pharmacokinetic behavior after rats were intravenously administered with pedunculoside or pedunculoside–βCDP. The results indicated that pedunculoside–βCDP could significantly improve the pharmacokinetic profile of pedunculoside by increasing plasma exposure, retarding elimination, and reducing intestinal metabolism. This study enhances our understanding of pedunculoside–βCDP’s metabolic fate and pharmacokinetic properties and potentially advances its further research, development, and clinical application.

Abstract p53 is the most highly mutated tumor suppressor across multiple types of human cancers. The level and function of p53 are fine-tuned through multifaced mechanisms in which the protein–protein interaction between p53 and MDM2 is considered as a major circuit. Recent studies suggest therapeutic strategy attempts to restore p53 function by small molecule inhibitors targeting p53–MDM2 interaction can be a promising direction in treating cancers with wild-type or functional p53. Currently, clinical tests of the p53–MDM2 protein–protein interaction inhibitors (PPIs) are underway. However, it remains elusive about the biomarkers that may predict the therapeutic responses to those inhibitors. Here we report that RNA-binding protein LIN28B directly regulates p53 through binding to the 5′΄ untranslated region of p53 mRNA and blocks its translation by competing with a translation enhancer protein, ribosomal protein L26 (RPL26). This regulatory mechanism of LIN28B does not involve let-7 maturation or the canonical protein turnover pathway of p53. Furthermore, we show that inhibition of LIN28B unleashes the translational suppression of p53 through RPL26, and leads to enhanced sensitivities of cancer cells to inhibitors of p53–MDM2 interaction. Together, we demonstrate a competitive regulatory mechanism of p53 by LIN28B, which has important implications in developing biomarkers to the therapies aiming to reinstate p53 function.

Cutting fluids are essential for the machining of difficult-to-cut materials in production. In addition to four basic functions including cooling, lubrication, cleaning, and antirust, cutting fluids also have an effect on the reduction of hardness and ductility of materials. Focused on the effect of cutting fluid composition in the material deformation processes, the influence of two universal cutting fluids (denoted as Blasocut and E709) on high strain rate dynamic mechanical properties of Ni-based superalloy was experimentally investigated and verified by cutting process. The shear stress-shear strain curve, maximum shear stress and shear failure stress, milling force as well as chip formation were systematically investigated. It is indicated that the results from Split Hopkinson Pressure Bar tests are consistent with those from cutting experiments. The Rehbinder effect for the samples under E709 conditions is more significant and the stress fluctuation is the largest, which is up to 14%. Brittle fracture exists under a narrow shear bandwidth 100 μm with high strain rate 10 × 104 s−1, while ductile fracture occurs under a wide shear bandwidth 400 μm with low strain rate 3 × 104 s−1. The cutting force amplitude under E709 is larger than that of Blasocut. The chip burrs under E709 and water are more severe than those under Blasocut. This research reveal significant connection between the cutting fluids and the dynamic mechanical properties or the cutting performance of the metal, which is also helpful to the control of mechanical properties and fatigue resistance of the machined surface.

The uncertainty and complexity of rock burst brings great difficulties to the prediction of rock burst grades. In order to estimate the risk grades of rock burst, an integrated method combining principal component analysis (PCA) and sparrow search algorithm (SSA) with probabilistic neural network (PNN) was proposed. Considering that the in situ stress of rock mass, the strength of rock, and the strength of rock mass are the key influencing factors of rock bursts, the maximum in situ stress σmax, maximum tangential stress σθ, rock strength σci, rock mass strength σcm, and three rock burst evaluation indexes (σθ/σci, σci/σmax, and σcm/σmax) were selected to constitute the rock burst grade evaluation index system. Forty-three groups of rock burst engineering data were gathered. After preprocessing the rock burst data using PCA, four of the new linearly independent indexes PCA1, PCA2, PCA3, and PCA4 were obtained for estimating rock burst grades. The SSA was utilized to optimize the smoothing factor in the PNN. Using PCA-SSA-PNN-based architecture, a new multi-index rock burst grade prediction method was proposed. The results from the new multi-index rock burst grade prediction method were compared with those from single- and multi-index prediction methods. It shows that the predictions from the multi-index rock burst prediction methods are closer to the actual rock burst grades than that from the single-index rock burst prediction methods; compared with other multi-index rock burst prediction methods, the prediction accuracy of PCA-SSA-PNN is greater (up to 90%) and more available in the prediction of rock burst grades. The results presented herein may provide reference for the rock burst warning.

BackgroundColorectal cancer (CRC) is the second leading cause of cancer death worldwide. Opportunistic colonoscopy may be beneficial in reducing the incidence of CRC by detecting its precursors.AimTo determine the risk of colorectal adenomas in a population who underwent opportunistic colonoscopy, and demonstrate the need for opportunistic colonoscopy.MethodsA questionnaire was distributed to patients who underwent colonoscopy in the First Affiliated Hospital of Zhejiang Chinese Medical University from December 2021 to January 2022. The patients were divided into two groups, the opportunistic colonoscopy group who underwent a health examination including colonoscopy without intestinal symptoms due to other diseases, and the non-opportunistic group. The risk of adenomas and influence factors were analyzed.ResultsPatients who underwent opportunistic colonoscopy had a similar risk to the non-opportunistic group, in terms of overall polyps (40.8% vs. 40.5%, P = 0.919), adenomas (25.8% vs. 27.6%, P = 0.581), advanced adenomas (8.7% vs. 8.6%, P = 0.902) and CRC (0.6% vs. 1.2%, P = 0.473). Patients with colorectal polyps and adenomas in the opportunistic colonoscopy group were younger (P = 0.004). There was no difference in the detection rate of polyps between patients who underwent colonoscopy as part of a health examination and those who underwent colonoscopy for other reasons. In patients with intestinal symptoms, abnormal intestinal motility and changes in stool characteristics were frequent (P = 0.014).ConclusionThe risk of overall colonic polyps, advanced adenomas in healthy people undergoing opportunistic colonoscopy no less than that in the patients with intestinal symptoms, positive FOBT, abnormal tumor markers, and who accepted re-colonoscopy after polypectomy. Our study indicates that more attention should be paid to the population without intestinal symptoms, especially smokers and those older than 40 years.

Objectives: To evaluate the effectiveness and safety of a newly designed self-assembling gel in treating ESD-induced gastric ulcers in patients.Methods: This open-label, multicenter, randomized controlled trial enrolled patients who underwent ESD between September 2020 and May 2021. Patients were randomized (1:1) to receive the gel (applied to cover the entire ulcer bed under endoscopic guidance immediately after ESD; gel group) or not (control group). The primary outcome was the ulcer healing rate at 28 days. And the secondary outcomes were the delayed bleeding, changes in the ulcer stage, and adverse events.Results: Finally, 125 patients (mean age, 63.7 years; 70 [56.0%] males) were enrolled. The ulcer healing rate was higher in the gel group than in the control group at 28 days (96.9 ± 4.1% vs. 94.7 ± 5.0%; p = 0.001). The ulcer reduction rate at 28 days differed significantly (p < 0.001) between ulcers with majority gel coverage (99.8%), ulcers with minority gel coverage (96.2%), and ulcers with no gel coverage (98.0%). Delayed bleeding was found in 1/63 gel-treated patients (1.6%) versus 5/62 controls (8.1%). A1-stage ulcers were found in 16/63 patients in the gel group versus 44/62 patients in the control group (25.4% vs. 71.0%, p < 0.001) at 3–5 days.Conclusion: The newly developed self-assembling gel was safe and effective in accelerating gastric ulcer healing in patients after ESD.Clinical Trial Registration: UMIN Clinical Trials Registry System (registration number, ChiCTR2100052935).

Abstract This paper proposes a common‐mode voltage injection‐based pulse width modulation strategy to optimize the AC current ripple of parallel interleaved converters. In general, modulation methods entail a trade‐off between switching times and voltage error. Given the redundancy in the available vector sequences, we sequentially minimize the switching times and the voltage error. Specifically, we propose eight candidate vector sequences with minimized switching times for each 60° sector. Then, we quantitate the current ripple introduced by the eight vector sequences, and according to the calculations, we split each 60° sector into eight subsectors, each employs the respectively optimal vector sequence with the minimized current ripple. For implementation, the candidate vector sequences are further unified by a common‐mode voltage injection scheme. The injection depends on the momentary subsector in which the reference lies. Despite the complex geometry of the subsectors, we propose a simple decision procedure that can be easily implemented in mainstream microcontrollers. Compared to the conventional methods, the proposed common‐mode voltage injection‐based pulse width modulation has a smaller AC current ripple at the same switching loss. The experimental results verify the theoretical analysis and the effectiveness of the proposed common‐mode voltage injection‐based pulse width modulation strategy.

BackgroundChronic atrophic gastritis (CAG) can progress to gastric cancer (GC) thus requiring endoscopic surveillance. Here, we analyze various aspects of CAG progression, time, and mucosal background, to guide reasonable surveillance.MethodsCAG patients with three or more endoscopies from 2010–2021 were included. All cases were analyzed for rate and time of progression, and cases with operative link on gastritis assessment (OLGA) staging, operative link on gastric intestinal metaplasia assessment (OLGIM) staging, and Kimura-Takemoto classification were further analyzed. Additional investigation of guideline-defined low-risk patients by reviewing endoscopy in the short-term (1–2 years) after baseline identified several patients as high-risk.ResultsNinety-seven (10.4%) of the 929 CAG patients progressed to low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), or GC, during the observation period of 36–129 months (median 53, IQR=24), including 75 (8.1%) cases of LGIN, eight (0.9%) of HGIN, and 14 (1.5%) of GC. Among 170 patients with OLGA/OLGIM at baseline, two (2/2, 100%) GC cases occurred in patients with OLGA/OLGIM III and IV. Of the 236 patients with Kimura-Takemoto classification at baseline, 5/7 (71.4%) cases of GC occurred in patients with C3–O3. Ten, 11, and 25 patients classified as low-risk on the European, British, and Chinese Guidelines, underwent additional endoscopy within 1–2 years, resulting in three (30.0%), four (36.4%), and eight (32.0%) patients being classified as high-risk on these guidelines, respectively.ConclusionA minority of CAG patients can progress to GC. OLGA/OLGIM III and IV staging are closely associated with progression. Disease-associated risk may be underestimated in one-third of patients classified as low-risk by initial endoscopy.

Tenofovir (TFV) ester prodrugs, a class of nucleotide analogs (NAs), are the first-line clinical anti-hepatitis B virus (HBV) drugs with potent antiviral efficacy, low resistance rate and high safety. In this work, three marketed TFV ester drugs, tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF) and tenofovir amibufenamide fumarate (TMF), were used as probes to investigate the relationships among prodrug structures, pharmacokinetic characteristics, metabolic activations, pharmacological responses and to reveal the key factors of TFV ester prodrug design. The results indicated that TMF and TAF exhibited significantly stronger inhibition of HBV DNA replication than did TDF in HBV-positive HepG2.2.15 cells. The anti-HBV activity of TMF was slightly stronger than TAF after 9 days of treatment (EC50 7.29 ± 0.71 nM vs. 12.17 ± 0.56 nM). Similar results were observed in the HBV decline period post drug administration to the HBV transgenic mouse model, although these three TFV prodrugs finally achieved the same anti-HBV effect after 42 days treatments. Furthermore, TFV ester prodrugs showed a correcting effect on disordered host hepatic biochemical metabolism, including TCA cycle, glycolysis, pentose phosphate pathway, purine/pyrimidine metabolism, amino acid metabolism, ketone body metabolism and phospholipid metabolism. The callback effects of the three TFV ester prodrugs were ranked as TMF > TAF > TDF. These advantages of TMF were believed to be attributed to its greater bioavailability in preclinical animals (SD rats, C57BL/6 mice and beagle dogs) and better target loading, especially in terms of the higher hepatic level of the pharmacologically active metabolite TFV-DP, which was tightly related to anti-HBV efficacy. Further analysis indicated that stability in intestinal fluid determined the actual amount of TFV prodrug at the absorption site, and hepatic/intestinal stability determined the maintenance amount of prodrug in circulation, both of which influenced the oral bioavailability of TFV prodrugs. In conclusion, our research revealed that improved pharmacokinetics of TFV ester prodrugs (especially intestinal stability) strengthened the inhibition of HBV replication and the rebalance of hepatocellular metabolism, which provides new insights and a basis for the design, modification and evaluation of new TFV prodrugs in the future.

This paper presents a machine learning-based approach to estimating the compressive strength and elastic modulus of rocks. A hybrid model, GWO-ELM, was built based on an extreme learning machine network optimized by the grey wolf algorithm. The proposed model was carried out on 101 experimental datasets, and four commonly used models were used as benchmarks to evaluate the accuracy of the proposed model. The results showed that the proposed hybrid model can accurately achieve the prediction of elastic modulus and compressive strength with high correlation coefficients and small prediction errors. The prediction performance of the hybrid model is significantly better than the other four original models, and it is an alternative model for predicting the compressive strength and elastic modulus of rocks, which is recommended as an auxiliary tool for real-time prediction of rock mechanical properties.

Signet ring cell carcinoma (SRCC) was previously thought to have a worse prognosis than differentiated gastric carcinoma (DC). However, recent studies have shown that its prognosis is related to staging. Here, we analyzed the clinicopathological features and the rate of lymph node metastasis (LNM) in 2166 patients with gastric cancer (605 early and 1561 advanced cases) who underwent gastrectomy and lymph node dissection (D2) from 2016 to 2019. The LNM rate for early and advanced cases was 18.0% and 74.2%, respectively. Regarding early cases, the LNM rate in SRCC was similar to that in DC (10% vs. 16.1%, p=0.224), and significantly lower than that in undifferentiated carcinoma (UDC; 10% vs. 23.3%, p=0.024). Tumor size, infiltration depth, pathological type, and mixed type were risk factors for LNM in early cases. Regarding intramucosal cases, the LNM rate in SRCC was similar to that in DC (4.3% vs. 3.7%, p=0.852), and significantly lower than that in UDC (11.2%). The LNM rate was significantly higher in submucosal than intramucosal cases (28.1% vs. 6.3%, p

Echinococcus multilocularis is a zoonotic tapeworm with great medical significance. In E. multilocularis-infected mice, parasite-derived let-7-5p (emu-let-7-5p) is present in the sera, but its role remains unclear. Using qPCR, ELISA and flow cytometry, the immunomodulatory effects of emu-let-7-5p were in vitro investigated using RAW264.7 macrophages. Compared with the control, emu-let-7-5p significantly downregulated IL-1α (p < 0.05), but anti-inflammatory cytokine genes remained to be stably expressed in the treated macrophages. Moreover, significantly decreased expression of ripk1 and nf-kB, key components in the LPS/TLR4 signaling pathway, was also observed in the emu-let-7-5p-transfected cells (p < 0.05). Furthermore, CD40 was upregulated in these transfected cells (p < 0.05), while CD86, CD54 and CD80 remained unchanged compared that in the control. These results demonstrate a property of emu-let-7-5p in regulation of immune functions of macrophages, making it be possibly involved in the pathogen-host interplay during E. multilocularis infection.

Robot-assisted technology is often used to perform endovascular catheterization surgeries, which generally depend on the flexible operability and the accurate force feedback of a robotic system. In this paper, an endovascular catheterization robotic system (ECRS) was developed to improve collaborative operation and haptic force feedback. A couple of operating handles were designed to maximize the use of the natural operations of surgeons on the master side, which is a flexible and ergonomic device. A magnetically controlled haptic force feedback structure is proposed based on hydrogel and solid magnetorheological (MR) fluid to offer a sense of haptic feedback to operators; this has potential influence on the field of force feedback. In addition, a unique tremor-reduction structure is introduced to enhance operating safety. Tracking performance experiments and in vitro experiments were conducted to evaluate the performance of the developed ECRS. According to these experimental results, the average translation-tracking error is 0.94 mm, and the average error of rotation is 0.89 degrees. Moreover, in vitro experiments demonstrated that haptic feedback has the advantage of reducing workload and shortening surgery completion time. The developed ECRS also has the benefits of inspiring other researchers to study collaborative robots and magnetically controlled feedback.

Although metabolic reprogramming and redox imbalance are widely reported to be involved in chemo-resistance in cancer treatment, much more attention was paid to anti-cancer drug induced effect. Our previous studies showed that cancer cells can develop P-gp overexpression-mediated intrinsic drug resistance in the formation of 3D MCF-7 multi-cellular layers (MCLs) without any drug induction. However, whether metabolic reprogramming and redox imbalance functioned during this progress remained unrevealed. In our present study, LC-Q/TOF-MS and GC-MS were used in combination for analysing intracellular metabolites. The contribution of pentose phosphate pathway (PPP) and its related redox status were checked by chemical interfering and silencing/over-expression of glucose-6-phosphate dehydrogenase (G6PD). The downstream products of G6PD were assayed by quantitative real-time PCR, western blot and flow cytometry. Results showed that not only G6PD expression but also G6PD activity was significantly lowered along with 3D MCF-7 cells culture time. Impaired PPP disturbed redox-cycling, generated reactive oxygen species (ROS), which triggered cell cycle arrest and caused the switch to Chk2/p53/NF-κB pathway-mediated P-gp induction. Our results provided a new attempt to associate intrinsic small molecule metabolites (impaired PPP) communicating with cell signalling pathways through disturbed intracellular redox status to elucidate multi-cellular resistance (MCR) in 3D MCF-7 cells, which improved the understanding of the mechanisms of P-gp up-regulation in MCR with metabolomic and related redox status support.

This paper proposes an operation safety early warning system based on LabView (2014, National Instruments Corporation, Austin, TX, USA) for vascular interventional surgery (VIS) robotic system. The system not only provides intuitive visual feedback information for the surgeon, but also has a safety early warning function. It is well known that blood vessels differ in their ability to withstand stress in different age groups, therefore, the operation safety early warning system based on LabView has a vascular safety threshold function that changes in real-time, which can be oriented to different age groups of patients and a broader applicable scope. In addition, the tracing performance of the slave manipulator to the master manipulator is also an important index for operation safety. Therefore, we also transformed the slave manipulator and integrated the displacement error compensation algorithm in order to improve the tracking ability of the slave manipulator to the master manipulator and reduce master–slave tracking errors. We performed experiments “in vitro” to validate the proposed system. According to previous studies, 0.12 N is the maximum force when the blood vessel wall has been penetrated. Experimental results showed that the proposed operation safety early warning system based on LabView combined with operating force feedback can effectively avoid excessive collisions between the surgical catheter and vessel wall to avoid vascular puncture. The force feedback error of the proposed system is maintained between ±20 mN, which is within the allowable safety range and meets our design requirements. Therefore, the proposed system can ensure the safety of surgery.

The machining mechanics of carbon fiber reinforced polymer (CFRP) materials are influenced by the coupled effects of the workpiece anisotropy, tool edge geometry, and cutting parameters. Predicting the chip formation mechanism is crucial for optimizing cutting parameters, reducing tool wear, and improving efficiency and surface quality. This study quantitatively evaluates the effect of main CFRP failure criteria on the chip formation mechanism in modeling the machining mechanics of CFRP. The results show that the Hashin-Puck and Dávila criteria excel at capturing chip formation across all fiber orientations because of the incorporation of the "internal friction" concept, while others only achieve accurate predictions in specific fiber orientation ranges due to improper shear strength consideration. The sources of the prediction similarities, differences, and limitations of failure criteria are experimentally validated. Sensitivity analyses quantitatively determine the effect of the tool rake angle on the machining energy consumption and cutting forces across the fiber orientation range. This research can be used to select the optimal failure criteria, design proper cutting tool geometry, and inform the cutting parameter choices for CFRP machining operations. [ABSTRACT FROM AUTHOR]

Shear localization is the dominant chip formation mechanism in machining of high-performance metallic components, such as those made of titanium and nickel-based alloys. This paper presents an analytical thermo-mechanical model considering a new tool-chip contact mechanism due to shear localization. First, it is experimentally shown that the sticking and sliding contact lengths fluctuate with the frequency of shear localization. Second, a cutting mechanics model is developed considering the shear band formation, its rolling on the tool's rake face, and the time-varying tool-chip contact length with experimental validation. Finally, the transient temperature at the tool-chip interface is predicted by taking the rolling phenomenon and the time-varying heat sources at the tool-chip interface into account. The proposed model shows that at the beginning of every segmentation cycle, the entire tool-chip contact length is dominated by sliding condition with negligible sticking length. When the tool advances, new workpiece material piles up in its front with an increase in the sticking length. Meanwhile, the sliding length decreases due to the drop in the load-bearing capacity of the shear band. When enough material piles up in front of the tool, a new shear band forms, and the entire contact length returns to the sliding condition. This process repeats every time a shear band occurs, causing the cyclic formation of shear bands and time-varying nature of the tool-chip contact length, therefore influencing the temperature and stress evolution at the tool-chip interface. [ABSTRACT FROM AUTHOR]

Background: This network meta-analysis was performed to assess the relative efficacy and safety of various regional analgesic techniques used in thoracic surgery. Materialsand methods: Randomized controlled trials evaluating different regional analgesic methods were retrieved from databases, including PubMed, Embase, Web of Science, and the Cochrane Library, from inception to March 2021. The surface under the cumulative ranking curve) was estimated to rank the therapies based on the Bayesian theorem. Moreover, sensitivity and subgroup analyses were performed on the primary outcomes to obtain more reliable conclusions. Results: Fifty-four trials (3360 patients) containing six different methods were included. Thoracic paravertebral block and erector spinae plane block (ESPB) were ranked the highest in reducing postoperative pain. As for total adverse reactions and postoperative nausea and vomiting, postoperative complications, and duration of hospitalization, ESPB was found to be superior to other methods. It should be noted that there were few differences between various methods for all outcomes. Conclusions: Available evidence suggests that ESPB might be the most effective and safest method for relieving pain after thoracic surgery, shortening the length of hospital stay and reducing the incidence of postoperative complications. [ABSTRACT FROM AUTHOR]