Locally advanced head and neck squamous cell carcinoma treatment efficacy and safety: a systematic review and network meta-analysis

Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 3% of new cancer cases and 3% of all deaths worldwide. Most HNSCC patients are locally advanced (LA) at diagnosis. The combination of radiotherapy (RT), chemotherapy, targeted therapy, and immunotherapy are the primary LA-HNSCC treatment options. Nevertheless, the choice of optimal LA-HNSCC treatment remains controversial. We systematically searched public databases for LA-HNSCC-related studies and assess treatment effectiveness and safety by assessing the objective response rate (ORR), ≥3 adverse events (AEs), overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), local-region control (LRC), and disease-specific survival (DSS). 126 randomized controlled clinical trials (RCTs) were included in this study. We show that concurrent RT with nimotuzumab or conventional concurrent chemo-radiotherapy (CCRT) had significantly better efficacy and long-term survival without increasing AEs than RT alone. Accelerated fractionated radiotherapy (AFRT) showed better efficiency than conventional fractionated RT, although it had higher AEs. In addition, concurrent cetuximab combined with RT failed to show a significant advantage over RT alone.Trial registration: PROSPERO CRD42022352127

Mechanisms and applications of radiation-induced oxidative stress in regulating cancer immunotherapy

Radiotherapy (RT) is an effective treatment option for cancer patients, which induces the production of reactive oxygen species (ROS) and causes oxidative stress (OS), leading to the death of tumor cells. OS not only causes apoptosis, autophagy and ferroptosis, but also affects tumor immune response. The combination of RT and immunotherapy has revolutionized the management of various cancers. In this process, OS caused by ROS plays a critical role. Specifically, RT-induced ROS can promote the release of tumor-associated antigens (TAAs), regulate the infiltration and differentiation of immune cells, manipulate the expression of immune checkpoints, and change the tumor immune microenvironment (TME). In this review, we briefly summarize several ways in which IR induces tumor cell death and discuss the interrelationship between RT-induced OS and antitumor immunity, with a focus on the interaction of ferroptosis with immunogenic death. We also summarize the potential mechanisms by which ROS regulates immune checkpoint expression, immune cells activity, and differentiation. In addition, we conclude the therapeutic opportunity improving radiotherapy in combination with immunotherapy by regulating OS, which may be beneficial for clinical treatment

Precise and Rapid Validation of Candidate Gene by Allele Specific Knockout With CRISPR/Cas9 in Wild Mice

It is a tempting goal to identify causative genes underlying phenotypic differences among inbred strains of mice, which is a huge reservoir of genetic resources to understand mammalian pathophysiology. In particular, the wild-derived mouse strains harbor enormous genetic variations that have been acquired during evolutionary divergence over 100s of 1000s of years. However, validating the genetic variation in non-classical strains was extremely difficult, until the advent of CRISPR/Cas9 genome editing tools. In this study, we first describe a T cell phenotype in both wild-derived PWD/PhJ parental mice and F1 hybrids, from a cross to C57BL/6 (B6) mice, and we isolate a genetic locus on Chr2, using linkage mapping and chromosome substitution mice. Importantly, we validate the identification of the functional gene controlling this T cell phenotype, Cd44, by allele specific knockout of the PWD copy, leaving the B6 copy completely intact. Our experiments using F1 mice with a dominant phenotype, allowed rapid validation of candidate genes by designing sgRNA PAM sequences that only target the DNA of the PWD genome. We obtained 10 animals derived from B6 eggs fertilized with PWD sperm cells which were subjected to microinjection of CRISPR/Cas9 gene targeting machinery. In the newborns of F1 hybrids, 80% (n = 10) had allele specific knockout of the candidate gene Cd44 of PWD origin, and no mice showed mistargeting of the B6 copy. In the resultant allele-specific knockout F1 mice, we observe full recovery of T cell phenotype. Therefore, our study provided a precise and rapid approach to functionally validate genes that could facilitate gene discovery in classic mouse genetics. More importantly, as we succeeded in genetic manipulation of mice, allele specific knockout could provide the possibility to inactivate disease alleles while keeping the normal allele of the gene intact in human cells

Cycling comfort on asphalt pavement: Influence of the pavement-tyre interface on vibration

Attainment of cycling comfort on urban roads encourages travelers to use bicycles more often, which has social and environment benefits such as to reduce congestion, air pollution and carbon emissions. Cycling vibration is responsible for the cyclists’ perception of (dis)comfort. How asphalt pavement's surface characteristics relate to cycling comfort, however, remains undiscovered. In this study, the cycling vibration intensity on 46 sections of 24 urban roads was tested using a dynamic cycling comfort measure system while the cyclists’ perception of vibration was identified via questionnaires; the cycling comfort was then defined based on the cycling vibration. To record the accurate pavement-tyre interface under a stable environment, a total of 19 pavement sections were scanned using a 3D digital camera. These 3D models were then 3D printed, which are used to conduct the pressure film test using a self-developed pavement-tyre interface test system. Three ranges of pressure films were adopted to characterize the pavement-tyre interface via 9 parameters, namely contact area (A c ), unit bearing area (B u ), stress intensity (S i ), stress uniformity (S u ), kurtosis (S ku ), spacing (Sp a ), maximum peak spacing (Sp max ), radius ratio (R r ) and fractal dimension (F d ), in consideration of the area characteristics, pressure amplitude, peak spacing and shape of the interface. Finally, the significant interface parameters were identified, and the regression model between interface parameters and cycling comfort was established. Results show that the cycling vibration was described to be ‘very comfortable’ when the human exposure to vibration level (a wv ) was less than 1.78 m/s 2 ; ‘comfortable’ when the a wv was between 1.78 m/s 2 and 2.20 m/s 2 ; and ‘uncomfortable’ when the a wv was greater than 2.20 m/s 2 . The average stress on rear wheel-pavement interface is higher than that of the front wheel. B u-0.6 , Sp a-0.6 , and F d-0.6 are significant to cycling vibration. The 2LW pressure film is recommended for use to measure the bicycle pavement-tyre interface. The recommended interface characteristics are less than 7 mm 2 of the unit bearing area, 6 mm of average spacing and 2.38 of fractal dimension. Finally, dense asphalt mixture performs better in providing cycling comfort than the gap-graded asphalt mixture. Results of this study contribute to current knowledge on bike lane comfort and pavement design, the findings should be interested in cyclists, transport planners, and road authorities

A Parallel Computing Approach to Spatial Neighboring Analysis of Large Amounts of Terrain Data Using Spark

Spatial neighboring analysis is an indispensable part of geo-raster spatial analysis. In the big data era, high-resolution raster data offer us abundant and valuable information, and also bring enormous computational challenges to the existing focal statistics algorithms. Simply employing the in-memory computing framework Spark to serve such applications might incur performance issues due to its lack of native support for spatial data. In this article, we present a Spark-based parallel computing approach for the focal algorithms of neighboring analysis. This approach implements efficient manipulation of large amounts of terrain data through three steps: (1) partitioning a raster digital elevation model (DEM) file into multiple square tile files by adopting a tile-based multifile storing strategy suitable for the Hadoop Distributed File System (HDFS), (2) performing the quintessential slope algorithm on these tile files using a dynamic calculation window (DCW) computing strategy, and (3) writing back and merging the calculation results into a whole raster file. Experiments with the digital elevation data of Australia show that the proposed computing approach can effectively improve the parallel performance of focal statistics algorithms. The results also show that the approach has almost the same calculation accuracy as that of ArcGIS. The proposed approach also exhibits good scalability when the number of Spark executors in clusters is increased

Hot Deformation Behavior and Hot Rolling Properties of a Nano-Y2O3 Addition Near-α Titanium Alloy

The hot deformation behavior and hot rolling based on the hot processing map of a nano-Y2O3 addition near-α titanium alloy were investigated. The isothermal compression tests were conducted at various deformation temperatures (950–1070 °C) and strain rates (0.001–1 s−1), up to a true strain of 1.2. The flow stress was strongly dependent on deformation temperature and strain rate, decreasing with increased temperature and decreased strain rate. The average activation energy was 657.8 kJ/mol and 405.9 kJ/mol in (α + β) and β region, respectively. The high activation energy and peak stress were contributed to the Y2O3 particles and refractory elements comparing with other alloys and composites. The deformation mechanisms in the (α + β) region were dynamic recovery and spheroidization of α phase, while the β phase field was mainly controlled by the dynamic recrystallization and dynamic recovery of β grains. Moreover, the constitutive equation based on Norton–Hoff equation and hot processing map were also obtained. Through the optimal processing window determined by the hot processing map at true strains of 0.2, 0.4 and 0.6, the alloy sheet with multi-pass hot rolling (1050 °C/0.03–1 s−1) was received directly from the as-cast alloy. The ultimate tensile strength and yield strength of the alloy sheet were 1168 MPa and 1091 MPa at room temperature, and 642 MPa and 535 MPa at 650 °C, respectively, which performs some advantages in current research

Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Copper is an indispensable micronutrient for the development and replication of all eukaryotes, and its redox properties are both harmful and beneficial to cells. An imbalance in copper homeostasis is thought to be involved in carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, and metastasis cannot be separated from the effects of copper. Cuproposis is a copper-dependent form of cell death that differs from other existing modalities of regulatory cell death. The role of cuproptosis in the pathogenesis of the nervous and cardiovascular systems has been widely studied; however, its impact on malignant tumors is yet to be fully understood from a clinical perspective. Exploring signaling pathways related to cuproptosis will undoubtedly provide a new perspective for the development of anti-tumor drugs in the future. Here, we systematically review the systemic and cellular metabolic processes of copper and the regulatory mechanisms of cuproptosis in cancer. In addition, we discuss the possibility of targeting copper ion drugs to prolong the survival of cancer patients, with an emphasis on the most representative copper ionophores and chelators. We suggest that attention should be paid to the potential value of copper in the treatment of specific cancers

WDR68 is essential for the transcriptional activation of the PRC1-AUTS2 complex and neuronal differentiation of mouse embryonic stem cells

Recent studies on Polycomb repressive complexes (PRC) reveal a surprising role in transcriptional activation, yet the underlying mechanism remains poorly understood. We previously identified a type 1 PRC (PRC1) that contains Autism Susceptibility Candidate 2 (AUTS2), which positively regulates transcription of neuronal genes. However, the mechanism by which the PRC1-AUTS2 complex influences neurodevelopment is unclear. Here we demonstrate that WDR68 is not only an integral component of the PRC1-AUTS2 complex, but it is also required for PRC1-AUTS2-mediated transcription activation. Furthermore, deletion of Wdr68 in mouse embryonic stem cells leads to defects in neuronal differentiation without affecting self-renewal. Through transcriptomic analysis, we found that many genes responsible for neuronal differentiation are down-regulated in Wdr68 deficient neural progenitors. These genes include those targeted by the PRC1-AUTS2 complex. In summary, our studies uncovered a previously unknown but essential component of the active PRC1 complex and evidence of its role in regulating the expression of genes that are important for neuronal differentiation. Keywords: Epigenetics, Stem cells, Transcription, Polycomb, Protein complex, Differentiatio

A Novel Model-Free Predictive Control for T-Type Three-Level Grid-Tied Inverters

The model-free predictive control (MFPC) scheme is an effective scheme to enhance the parameter robustness of model predictive control. However, the MFPC scheme can be affected by the current gradient updating frequency. This paper proposes an improved MFPC scheme for a T-type three-level inverter. First, a novel current gradient updating method is designed to estimate all current gradients per control period, which uses the current gradient relationship between different voltage vectors and eliminates the effect of current gradients updating stagnation. Moreover, a sector judgment method based on the current gradient is proposed. Redundant small vectors are accurately judged and the computational burden is greatly reduced. Finally, simulation and experimental comparisons on a T-type three-level inverter verify the effectiveness of the proposed MFPC scheme

A Block-Scale FFT Filter Based on Spatial Autocorrelation Features of Speckle Noise in SAR Image

In order to reduce the impact of noise on the accuracy of inversion products based on SAR images, many filtering algorithms have been developed for noise reduction of SAR images. This paper proposes a filtering method based on the spatial autocorrelation feature of the block fast Fourier transform (BFFT). The method statistically analyses the autocorrelation length of speckle noise on Sentinel-1B images for different features and then constructs a relationship between autocorrelation length and noise period. After that, the size of the optimal FFT filtering window radius was determined based on the relationship between the noise period and the components in the image frequency domain. Finally, we filtered the SAR image within the parcels. We compared BFFT with six commonly used filtering methods. The results show that: (1) The noise periods of the soybean, corn, paddy, and water objects on the SAR image have little difference, with noise periods of 3.36, 3.17, 3.13, and 3.14 pixels on the VV polarization and 3.49, 3.17, 2.94, and 2.42 pixels on the VH polarization; (2) after the BFFT filtering in the land parcel area, the mean value of the backscattering coefficient (BC) kept constant, whilst at the same time, the standard deviation (STD) was reduced to half of that before the filtering and (3) the BFFT and NLM filtering methods have a better effect on noise reduction inside the block. The BFFT filtering method retains the variation trend between different regions within the block and preserves the block boundary’s clarity. This study provides a new idea for refined image processing