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The role of autophagy in cancer remains elusive, and nontargeted autophagy inhibitors have limited therapeutic effects in HNSCC. Here, we systematically analyzed the correlation of autophagy-related genes in HNSCC through TCGA and single-cell sequencing data (GSE103322). ATG9B and ATG7 were found to have noncanonical autophagy-independent functions in HNSCC. Specifically, ATG9B was a protective factor in HNSCC patients through downregulating cancer cell EMT, and ATG7 was correlated with the immunosuppressive environment in HNSCC. Mechanistically, single-cell analysis revealed that ATG9B increased the epithelial phenotype of cancer cells but did not influence EMT signaling pathways. ATG7 was strongly correlated with elevated immunosuppressive checkpoints like PD-1, PD-L1, and CTLA4 in HNSCC. Further single-cell analysis and multiple immunofluorescence colocalization analyses indicated that ATG7 contributed to the high expression of PD-L1 in myeloid cells but not cancer cells. Collectively, our results revealed noncanonical autophagy-independent functions of autophagy-related genes. These results increase understanding of the intricacies of autophagy and may contribute to precision treatment using autophagy-targeted therapies.

Background: The aims of our article were to identify the core genes of the autophagy-related genes (ARGs) which abnormally expressed in laryngeal cancer (LC) and constructed a risk prognostic models with these genes. Methods: In this study, we identified genes with abnormally expressed in LC, and they were mainly involved in some cancer-related gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG). Statistical analysis were conducted to identify the powerful independent prognostic factors associated with clinical factors and survival. Results: A total of 35 DEGs were identified in our research. The risk prediction model was constructed with three potential prognostic genes (VEGFA, SPNS1 and CCL2) of autophagy by lasso regression analysis that can successfully predict the prognosis in LC. We applied ROC curve to evaluate the effectiveness of the risk prognostic model, and found that AUC was 0.693 below the curve. Risk prediction model was only related to survival status (P < 0.01), and was not related to clinicopathological factors. Furthermore, the genes (VEGFA and CCL2) were considered as core genes not only because they were the highly connected genes but also they were the composed genes of risk prognostic model. Conclusions: Taken together, ARGs were considered as important roles in the progression of LC and the prognostic model can help to identification of new targets to guide the diagnosis and therapy.

Wet removal is the primary method for the natural removal of atmospheric aerosol particles, and wet removal is a very complex process. According to the PM2.5, PM10, and meteorological data from 71 cities in China from 2016 to 2018, this study utilizes theoretical analysis methods based on the existing rainfall aerosol removal theory and real-time monitoring data to calculate the measured removal coefficient and theoretical removal coefficient for verification. According to the different rainfall intensities and rainfall times in Guilin, the measured value and the simulated value are verified, and the linear relationship obtained was Λs = 1.589*10− 5 + 0.609Λm, R2 = 0.673, and the simulated value approximated to the measured value after correction. The same method was utilized to calculate the theoretical removal coefficient of polydisperse aerosols in 71 cities across the country, and the calculation parameters of the rainfall removal polydisperse aerosol model in different regions were modified.

Based on five consecutive years of measured data from January 2008 to December 2012 at representative observation sites in Shanghai, we analyzed the fine particle mass concentrations and their variation characteristics. The main conclusions drawn are as follows: the annual average mass concentrations of PM (including PM1, PM2.5 and PM10) in Shanghai city exhibited a decreasing trend. PM1 decreased from 46.7 ± 34.7 to 32.1 ± 25.4 µg/m3 (annual mean ± standard deviation), PM2.5 decreased from 53.2 ± 37.4 to 36.7 ± 26.9 µg/m3 and PM10 decreased from 70.2 ± 46.7 to 49.2 ± 34.7 µg/m3. In terms of the 5-year average mass concentrations, PM1, PM1–2.5 (particulate matter with a particle size dp of 1–2.5 µm) and PM2.5–10 (particulate matter with a dp of 2.5–10 µm) accounted for about 61.1%, 11.3% and 27.6% of PM10, respectively. The seasonal average mass concentrations of PM1, PM2.5 and PM10 from 2008 to 2012 were highest in winter, followed by autumn and lowest in summer. The average mass concentration of PM1–10 (particulate matter with a dp of 1–10 µm) was 2.2, 1.7 and 1.4 times higher in spring than in summer, autumn and winter, respectively. The proportion of PM1–10 to PM10 was 48.9%, 37.0%, 35.9% and 33.3% in spring, summer, autumn and winter. In spring, Shanghai was affected by sand and dust aerosols from northern China and more severely by PM1–10 from Zhejiang, Jiangxi and Fujian; in autumn and winter, Shanghai was more influenced by PM1–10 from Henan, Hubei and Anhui.

Guang Yang,1,2 Yisong Yan,1,3 Jun Mao,1 Huiping Liu,1 Mingtao Chen,1 Na Zhang,1 Yaowen Li,1 Jiangjun Gu,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Pharmacy, The Third People’s Hospital of Tongling, Tongling, Anhui, People’s Republic of China; 3Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Wuhu, Anhui, People’s Republic of ChinaCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Meishan Road 81#, Hefei, Anhui, 230032, People’s Republic of ChinaTel +86 138 5518 3138Email math2088@163.comBackground: Linezolid (LNZ), an oxazolidinone antibiotic, has 100% oral bioavailability and favorable activities against gram-positive pathogens. The in vitro PK/PD model was developed based on concentrations obtained with routine doses in humans can be used to guide dose optimization in the clinic.Methods: In this study, we employed an in vitro PK/PD model to simulate the changes in the plasma concentration of linezolid in the human body against a clinical isolate of MRSA in vitro. A high-performance liquid chromatography (HPLC)-UV method was applied to measure the concentration of linezolid. Bacterial samples were collected at different times from the central compartment for count.Results: The chromatographic separation was carried out with an AichromBond-AQC18 column(250mm× 4.6mm, 5μm), using a mobile phase of water with 0.1% formic acid:acetonitrile 70:30 (v/v), followed by detection at 254 nm, and a single detection run was completed within 10 min. The method was validated by estimating the precision and accuracy for the inter- and intra-day analyses in the concentration range of 0.25– 32 mg/L. The method was linear over the investigated range of 0.125– 32 mg/L, with all correlation coef&filig;cients R2 = 0.9999. The intra-day and inter-day precisions were within 7.598%, and the method recovery ranged from 90.912% to 106.459%. In vitro PK/PD model, both the absorption and elimination of linezolid being simulated can be precisely controlled by computer. In the control group, the bacterial reached 7.9 Log10CFU/mL in the &filig;rst 48h and maintained until the end, indicating that the colonies grew well in vitro PK/PD model. In the linezolid 600 mg q12h administration group, the colony decreased to 2.39 Log10CFU/mL at 24h, showing a good bactericidal effect; however, the colonies resumed growth to the initial level in 48h, indicating an emergence of resistance.Conclusion: We successfully established an in vitro infection PK/PD model and developed an HPLC-UV method to determine linezolid concentration for resistance investigation. The results suggest that the 600 mg q12h dosing regimen may no longer be applicable and requires optimization.Keywords: linezolid, HPLC-UV, PK/PD model, resistance

Objective Although perineural invasion (PNI) is well-known to be correlated with and able to predict lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC), the clinical and molecular correlation between PNI and LNM has not been elucidated, and preoperative biomarkers for LNM prediction in OSCC are urgently needed. Materials and methods The correlation between PNI and LNM was retrospectively evaluated using a cohort of 218 patients diagnosed with OSCC. Candidate neuropeptides were screened based on TCGA database and verified via immunohistochemistry and Western blot analyses. ELISA was used to detect calcitonin gene-related peptide (CGRP) in patient plasma. In vitro assays were used to explore the effects of CGRP on OSCC cells. Results OSCC patients with PNI had a higher incidence of LNM (69.86% vs. 26.2%, P n = 218). CGRP expression was upregulated in the PNI niche and in metastatic lymph nodes, and was correlated with poor overall survival of OSCC patients. Preoperative plasma CGRP levels were higher in OSCC patients (n = 70) compared to healthy donors (n = 60) (48.59 vs. 14.58 pg/ml, P P P = 0.0002). Preoperative plasma CGRP levels alone yielded an AUC value of 0.8088 to predict LNM, and CGRP levels combined with preoperative T stage reached an AUC value of 0.8590. CGRP promoted proliferation and migration abilities of OSCC cells, which could be antagonized by either pharmacological or genetic blockade of the CGRP receptor. Conclusions The neuropeptide CGRP links PNI and LNM in OSCC, and preoperative plasma CGRP levels can be used to predict LNM in OSCC.

Natural gas hydrate (NGH) exploitation is severely restricted by geotechnical problems. Deformation behaviors of the hydrate-bearing strata (HBS) control the occurrence and evolution of geotechnical problems during extracting natural gas from HBS. In this paper, a novel approach named Ladetes is introduced to evaluate the lateral deformation behaviors of the near-wellbore and fracture-filling regions of the HBS. The pressuremeter test and the flat dilatometer test are designed to simulate the inner boundaries of an NGH-producing well and an artificial stimulation fracture for the first time. The device can realize the in situ hydrate formation prior to the experiment and axial loading application throughout the experiment. Both the strain control mode and the stress control mode can be achieved to estimate the deformation characteristics of HBS under different downhole conditions. Prime experiments proved their adaptability and reliability. The Ladetes provides an effective and alternative way of obtaining geotechnical parameters for HBS.

Cell engineering, soft robotics, and wearable electronics often desire soft materials that are easy to deform, self-heal readily, and can relax stress rapidly. Hydrogels, a type of hydrophilic networks, are such kind of materials that can be made responsive to environmental stimuli. However, conventional hydrogels often suffer from poor stretchability and repairability. Here, hydrogels consisting of boronic ester dynamic covalent bonds in a double network of poly(vinyl alcohol)/boric acid and chitosan are synthesized, which demonstrate extreme stretchability (up to 310 times the original length), instant self-healing (within 5 s), and reusability and inherent adhesion. Their instant stress relaxation stems from a low activation energy of the boronic ester bond exchange (≤20 kJ mol

Particulate matter pollution is the cause of many diseases and the focus of urban atmospheric environmental research. Here, the spatiotemporal variations of PM2.5 and PM10 concentrations were analyzed across 71 cities in China using spatiotemporal sequence analyses and spatial interpolation of national monitoring data collected between 2016 and 2018. Significant differences were observed in the spatiotemporal variations of PM2.5 and PM10 concentrations across the country. PM2.5 concentrations in winter, spring, autumn, and summer were 60.16, 41.95, 37.10, and 26.94 µg/m3, respectively. The PM10 concentrations in spring and winter exhibited little difference at 89.50 and 92.30 µg/m3, respectively, but were higher than values observed in autumn and summer. The national annual average PM2.5 concentration decreased from 44.94 µg/m3 in 2016 to 37.75 µg/m3 in 2018, while that of PM10 decreased from 80.42 to 70.14 µg/m3. From 2016 to 2018, the monthly average concentrations of PM2.5 and PM10 in the 71 cities generally showed a downward trend. The average PM2.5 concentration in May comprised a single yearly peak, while the average PM10 concentration in October exhibited a second peak. The national PM2.5 and PM10 concentrations began to rise in September and October of each year and then decline in March and April of the next year. Spatial variation analysis revealed that the Hu Huanyong line is the east-west boundary line differentiating China's PM2.5 and PM10 concentrations (excluding Xinjiang), while the Yangtze River is the north-south boundary line. High pollution areas were mainly distributed in fast-growing urban agglomerations for instance the Central Plains, Bohai, and Yangtze River Delta urban agglomerations, in addition to the Xinjiang region. The annual average PM2.5 mass concentrations across the seven geographic regions of China followed the order of Central > North > Northwest > Northeast > East > Southwest > South China. Further, the annual average PM10 mass concentration followed the order of Northwest > Central > North > Northeast > North > Southwest > South China. From a spatial perspective, the PM2.5 and PM10 concentrations began to rise in September and October every year, then gradually spread outward from the Shandong, Shanxi, Henan, and Hebei provinces. The monthly increases comprised about 10–20 µg/m3, while the PM2.5 average concentration in most areas south of the Yangtze River exceeded 60 µg/m3 in May. Further, from March and April of the next year, a high-value area centered around Henan began to gradually decrease, and the division of concentrations between the north and south via the Yangtze River became more obvious.

Methylene blue as tracer used in sentinel lymph node biopsy (SLNB) have low detection rate and high false negative rate. Indocyanine green (ICG) can detect the flow of subcutaneous lymphatic vessels and the position of lymph nodes dynamically. This study sought to evaluate the efficacy of ICG combined with methylene blue staining in SLNB of breast cancer.One hundred and fifty-six early breast cancer patients treated at our hospital from July 2020 to May 2022 were enrolled in this study. SLNB was performed by ICG combined with methylene blue staining under the guidance of the fluorescent tracer navigation system FLI-10B. Standard axillary lymph node dissection (ALND) was performed in patients with sentinel lymph node (SLN) metastasis confirmed by intraoperative frozen pathology, while low ALND was performed in patients with negative SLNs. According to the staining condition, the SLNs were divided into: (I) the combined group (SLNs with methylene blue staining and/or ICG luminescence); (II) the methylene blue group (SLNs with methylene blue staining alone); and (III) the ICG group (SLNs with ICG luminescence alone). The detection rate, accuracy, sensitivity, and false negative rate of SLNB were compared among the 3 groups.A total of 592 SLNs were detected in the combined group (average 3.8 SLNs), yielding a detection rate of 97.4%; the accuracy, sensitivity, and false negative rates were 97.4%, 92.7%, and 7.3%. In the methylene blue group, 390 SLNs were detected (average 2.5 SLNs), yielding a detection rate of 84.6%; the accuracy, sensitivity, and false negative rates were 83.3%, 89.1%, and 10.9%. A total of 483 SLNs were detected in the ICG group (average 3.1 SLNs), the detection rate was 92.9%; the accuracy, sensitivity and false negative rates were 91.7%, 90.9%, and 9.1%. The average number of detected SLNs, detection rate and accuracy rate in the combined group were higher than those in the methylene blue group (P0.05), and the accuracy rate of the combined group was higher than that of the ICG group (P0.05).ICG combined with methylene blue staining is a promising and effective tracing strategy in the SLNB of breast cancer with high detection and accuracy rates.

Adhesives typically fall into two categories: those that have high but irreversible adhesion strength due to the formation of covalent bonds at the interface and are slow to deploy, and others that are fast to deploy and the adhesion is reversible but weak in strength due to formation of noncovalent bonds. Synergizing the advantages from both categories remains challenging but pivotal for the development of the next generation of wound dressing adhesives. Here, we report a fast and reversible adhesive consisting of dynamic boronic ester covalent bonds, formed between poly(vinyl alcohol) (PVA) and boric acid (BA) for potential use as a wound dressing adhesive. Mechanical testing shows that the adhesive film has strength in shear of 61 N/cm 2 and transcutaneous adhesive strength of 511 N/cm 2 , generated within 2 min of application. Yet the film can be effortlessly debonded when exposed to excess water. The mechanical properties of PVA/BA adhesives are tunable by varying the cross-linking density. Within seconds of activation by water, the surface boronic ester bonds in the PVA/BA film undergo fast debonding and instant softening, leading to conformal contact with the adherends and reformation of the boronic ester bonds at the interface. Meanwhile, the bulk film remains dehydrated to offer efficient load transmission, which is important to achieve strong adhesion without delamination at the interface. Whether the substrate surface is smooth (e.g., glass) or rough (e.g., hairy mouse skin), PVA/BA adhesives demonstrate superior adhesion compared to the most widely used topical skin adhesive in clinical medicine, Dermabond.

The introduction of cyclin-dependent kinase (CDK) 4 and 6 dual inhibitors significantly improves the progression-free survival of patients with ER+/HER2- advanced or metastatic breast cancer. A large cohort of patients, however, eventually relapse to CDK4/6 therapy. To further empower the CDK therapy, simultaneous targeting of CDK2, CDK4, and CDK6 has been proposed as a new strategy based on the finding that abnormal activation of CDK2/CyclinE1 due to CCNE1 gene amplification is determined the key resistant mechanism to CDK4/6 inhibition. Here we present preclinical data of TY-0540, a novel CDK2/4/6 inhibitor for the treatment of breast cancer that is resistant to CDK4/6 inhibition. TY-0540 demonstrates high selectivity against CDK2, CDK4, and CDK6 compared to that of CDK1, CDK7, and CDK9 in a CDK panel screening. In vitro cell proliferation data shows that tumor cell lines OVCAR3 and HCC1806, both bearing CCNE1 amplification, are highly sensitive to TY-0540 treatment. To test the effectiveness of the clinical candidate compound on CDK4/6i resistance models, two Palbociclib resistant cell populations (T47D-R, HCC1428-R) were in-house generated via gradient exposure of the cells to Palbociclib. As expected, TY-0540 potently inhibits T47D-R and HCC1428-R cell proliferation whereas Palbociclib only confers mild interruption to cell proliferation. TY-0540 abolishes Rb phosphorylation at all its three phosphorylation sites and down-regulates E2F1, FOXM1, and c-Myc expression levels in the model cell line OVCAR3. Meanwhile, cell cycle analysis suggests the occurrence of strong G1 arrest at 24 hours after TY-0540 treatment. Consistent with the in vitro results, TY-0540 treatment confers extraordinary in vivo efficacy with a spectrum of tumor CDX mouse models and PDX models in mice. To examine the in vivo effectiveness of TY-0540 over resistance models to CDK4/6 inhibition, we developed Palbociclib-resistant MCF7 tumor model (Palbociclib-R-MCF7) through a combination of in vitro and in vivo evolution of the cells under the selection pressure of Palbociclib. In agreement with its mode of action, TY-0540 is able to suppress Palbociclib-R-MCF7 tumor growth and maintain tumor size at stable disease status. Taken together, we have identified a potent CDK2/4/6 inhibitor which may grant new therapeutic opportunities for cancer patients who relapse or refractory to CDK4/6 signaling blockage therapy. #Meihua Li and Chengshan Niu contributed equally to this work. *Jun Li, Meihua Li and Chengshan Niu are the correspondent authors. Citation Format: Meihua Li, Chengshan Niu, Mingtao Chen, Kaige Ji, Hui Xu, Shengli Dong, Yan Zhang, Qinguo Meng, Yuge Dou, Yijun Wang, Rui Wu, Yian Tu, Chao Zhou, Apeng Liang, Huan Wang, Rongzhen Ni, Aishen Gong, Hui Su, Mingyu Jiang, Feng Xing, Shaoqing Chen, Xiugui Chen, Jun Li, Yusheng Wu. TY-0540, a highly potent CDK2/4/6 inhibitor, attenuates acquired resistance against CDK4/6 inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5979.

Purpose To investigate whether preoperative histogram parameters of dynamic contrast‐enhanced MRI (DCE‐MRI) can assess the expression of Ki‐67 in prostate cancer (PCa). Materials and methods A consecutive series of 76 patients with pathology‐proven PCa who underwent routine DCE‐MRI scans were retrospectively recruited. Quantitative parameters including the volume transfer constant (Ktrans), rate contrast (Kep), extracellular‐extravascular volume fraction (Ve), and plasma volume (Vp) by outlining the three‐dimensional volume of interest (VOI) of all lesions were processed. Then, the histogram analyses of these quantitative parameters were performed. The Spearman rank correlation analysis was used to evaluate the correlation of these parameters and Ki‐67 expression of PCa. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the efficacy of these quantitative histogram parameters in identifying high Ki‐67 expression from low Ki‐67 expression of PCa. Results Eighty‐eight PCa lesions were enrolled in this study, including 31 lesions with high Ki‐67 expression and 57 lesions with low Ki‐67 expression. The median, mean, 75th percentile, and 90th percentile derived from Ktrans and Kep had a moderately positive correlation with Ki‐67 expression (r = 0.361–0.450, p, In this work, we found that the median, mean, 75th percentile, and 90th percentile derived from Ktrans and Kep had a moderately positive correlation with Ki‐67 expression. We also chose the histogram quantitative parameters with an r value ≥0.4 to discriminate high Ki‐67 expression from low Ki‐67 expression in PCa. And six histogram parameters derived from Ktrans and Kep were selected, in which the AUC of mean for Ktrans was the highest (0.826).

Functional nanogels are attractive additives for use in polymer composites. In this study, nanogels with internal allyl sulfide moieties throughout their network structure were prepared via a thiol-Michael addition reaction. The excess thiol-functionalized nanogels were less than 60 nm as discrete particles but act as room-temperature liquids in the bulk state. The reactive nanogels can be dispersed in and swollen by a thiol-ene matrix resin, which upon photopolymerization yields dramatically decreased levels of polymerization shrinkage stress. Furthermore, the postcured nanogel-modified polymers effectively relaxed applied stresses as well as enhanced toughness during exposure to a UV light source that activated the addition-fragmentation as a means for dynamic bond exchange. These nanogels provide a generic approach to introduce adaptable network performance that significantly improves a number of key properties of glassy cross-linked polymer.

Clarifying the creep behaviors of hydrate-bearing sediment (HBS) under long-term loading is crucial for evaluating reservoir stability during hydrate exploitation. Figuring out a way of characterizing deformation behaviors and their geophysical responses to HBS is the basis for modeling creep behaviors. In this study, we propose a novel device to test time-dependent deformation and the ultrasonic response of HBS under high-pressure and low-temperature. The experimental device consists of a high-pressure chamber, an axial-load control system, a confining pressure system, a pore pressure system, a back-pressure system, and a data collection system. This testing assembly allows temperature regulation and independent control of four pressures, e.g., confining pressure, pore pressure, back pressure, and axial loading. Columned artificial HBS samples, with a diameter of 39 mm and a height of 120 mm, can be synthesized in this device. Afterward, in situ creep experiments can be achieved by applying stable confining pressure and axial load, together with geophysical signals acquisition. During loading, the stress–strain relationships and ultrasonic data can be obtained simultaneously. Through analyzing the stress–strain relationship and ultrasonic data, the macroscopical failure and microcosmical creep deformation law of the samples can be figured out. Preliminary experiments verified the applicability of the device. The method provides some significance for field observation of reservoir failure via geophysical techniques during hydrate exploitation.

The booming development of data science and big data technology stacks has inspired continuous iterative updates of data science research or working methods. At present, the granularity of the labor division between data science and big data is more refined. Traditional work methods, from work infrastructure environment construction to data modelling and analysis of working methods, will greatly delay work and research efficiency. In this paper, we focus on the purpose of the current friendly collaboration of the data science team to build data science and big data analysis application platform based on microservices architecture for education or nonprofessional research field. In the environment based on microservices that facilitates updating the components of each component, the platform has a personal code experiment environment that integrates JupyterHub based on Spark and HDFS for multiuser use and a visualized modelling tools which follow the modular design of data science engineering based on Greenplum in-database analysis. The entire web service system is developed based on spring boot.

Although nutrient-starvation therapies can elicit strong anti-tumor effects in multiple carcinomas, it has been convincingly demonstrated that cancer cells exploit the tumor microenvironment to thrive in nutrient-poor environments. Here, we reveal that cancer cells can co-opt nociceptive nerves to thrive in nutrient-poor environments. Initially examining the low-glucose environment of oral mucosa carcinomas, we discovered that cancer cells employ ROS-triggered activation of c-Jun to secrete nerve growth factor (NGF), which conditions nociceptive nerves for calcitonin gene-related peptide (CGRP) production. The neurogenic CGRP subsequently induces cytoprotective autophagy in cancer cells through Rap1-mediated disruption of the mTOR-Raptor interaction. Both anti-glycolysis and anti-angiogenesis-based nutrient-starvation therapies aggravate the vicious cycle of cancer cells and nociceptive nerves and therapeutically benefit from blocking neurogenic CGRP with an FDA-approved antimigraine drug. Our study sheds light on the role of the nociceptive nerve as a microenvironmental accomplice of cancer progression in nutrient-poor environments and upon nutrient-starvation therapies.

Data-intensive applications are becoming increasingly popular. However, only a few of them with high volume can afford dedicated hardware acceleration (such as Neural Network Processor, or NPU) or platform-specific software implementation (such as Tensorflow running on GPU). In this paper, we propose a hardware and software transparent framework for the acceleration of general-purpose data-intensive applications. Our framework is based on a key insight that most data-intensive applications spend the vast majority of their execution time on some inner loops with abundant opportunities for Data-Level Parallelism (DLP). In particular, we propose SALAD, a static analyzer for loop acceleration by exploiting DLP in hot loops under the LLVM (LLVM compiler infrastructure) framework. In contrast to traditional DLP exploration techniques, SALAD is both software and architectural transparent, without the need to change either the source code or binary code, and does not need vectorized instruction set architecture (ISA) extensions. Instead, it directly works on the program binary code and generates a profile for DLP opportunities in the binary. This profile will be fed to the hardware accelerator transparently to speed up execution. With the experiments result, we estimate that the DLP information provided by SALAD could result in 3.6x-60.2x speedups on a set of benchmarks, depending on their inherent DLP.

Exploiting inter-iteration data-level parallelism (DLP) is the important focus of many loop accelerators. Target at this, we propose a loop parallelization acceleration framework LoopPara, which follows a hardware/software coordinated pipeline: 1) an offline parallelism analysis is used to extract and encode application behavioral semantic of loop instructions as configuration. 2) a specialized loop accelerator loads the configuration for hardware mapping and guide the loop parallelism execution. Unlike traditional loop accelerators, LoopPara does not need instruction set architecture (ISA) extension, compiler modification, and software kernel replacement, which has better platform portability and can be easily integrated with general- propose processors with any ISA. Experiments show that, when coupling to an in-order RISC-V Rocket core, the LoopPara achieves 2.31x-5.42x (4. $17\mathrm{x}$ on average) speedups, which out- performs other high-performance out-of-order BOOM cores.

Ion dynamics in a series of imidazolium-based triblock copolymers (triblock co-PILs) are investigated using broadband dielectric spectroscopy (BDS) and differential scanning calorimetry (DSC) and compared to their homopolymer counterparts (homo-PILs). Two calorimetric glass transition temperatures (Tg) are observed corresponding to the charged poly(ionic liquid) (PIL) blocks and noncharged polystyrene (PS) blocks. Varying the counterion from Br– to NTf2– decreases the Tg of the charged block by over 50 °C, thereby increasing the room-temperature ionic dc conductivity by over 6 orders of magnitude. Interestingly, for a given anion, varying the volume fraction of the charged block, from ∼0.5 to ∼0.8, has very minimal effect on the dc ionic conductivity, indicating that the choice of counterion is the key factor influencing charge transport in these systems.

Commercial exploitation of marine natural gas hydrate (NGH) is crucial for energy decarbonization. However, hydrate production would weaken reservoir mechanical properties and trigger geohazards. Experimental instruments are the basis to obtain the mechanical responses of hydrate-bearing sediments (HBS). Considering the reservoir deformation processes from elastic deformation to residual deformation during hydrate exploitation, this study comprehensively reviewed the feasibility and mechanical research progress of the bender element, resonance column, atomic force microscope, triaxial shear, direct shear, ring shear, and static penetration in mechanical testing. Each test method’s precision and sample size were comprehensively compared and analyzed. Finally, the limitations and challenges of the current mechanical testing methods for HBS were discussed, and their future development directions were proposed. The proposed development direction in mechanical testing methods is expected to provide insightful guidance for the development of instruments and improve the understanding of the mechanical behavior of HBS.

Ionic liquids (ILs) and poly(ionic liquid)s (PILs) are attracting significant research interest as safe and efficient electrolytes. Most research efforts focus on nitrogen based ILs and PILs (ammonium, imidazolium, pyridinium, etc.), while phosphorus based ILs and PILs have received relatively less attention despite exhibiting comparable ion conductivity over their nitrogen-based counterparts. In this review, we provide an overview of the structural elements in phosphorus based ILs and PILs that influence ion conductivity, such as ion size, ion polarizability, counterion selection, and backbone flexibility. We also highlight dominant physical parameters dictating ion conductivity including viscosity and glass transition temperature. A fundamental understanding of this structure-ion conductivity relationship will benefit the future rational design of phosphorus based ILs and PILs as electrolytes.

Na Xie,1 Lifang Jiang,1 Mingtao Chen,1 Guijun Zhang,1 Yanyan Liu,2 Jiabin Li,2 Xiaohui Huang1 1Department of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Xiaohui HuangDepartment of Basic and Clinical Pharmacology, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui Province, 230032, People’s Republic of ChinaTel +86 138 5518 3138Email math2088@163.comJiabin LiDepartment of Infectious Diseases, The First Affiliated Hospital of Anhui Medical University, Jixi Road, 218#, Hefei, Anhui Province, 230032, People’s Republic of ChinaFax +86 551 62922713Email lijiabin@ahmu.edu.cnObjective: The purpose of this study is to assess the in vitro/vivo activities of linezolid plus fosfomycin against Staphylococcus aureus (S. aureus) isolates with varying susceptibility to the study drugs.Methods: The increasing concentration stepwise method was used to induce S. aureus resistant strains. The in vitro antibacterial activity of linezolid combined with fosfomycin against S. aureus in vitro was studied by time-kill curve and PAE. The transmission electron microscopy (TEM) was employed to observe the cell morphology of bacteria treated with drug, and the changes of cell wall thickness were recorded. The Galleria mellonella infection model was established to demonstrate the in vivo efficacy of linezolid and fosfomycin against S. aureus with varying susceptibility.Results: The antibiotic combination showed excellent synergistic or additive effects on the original and the linezolid-resistant strain, but showed indifferent effect for fosfomycin-resistant strain. TEM images showed that fosfomycin alone and in combined could reduce the cell wall thickness of the strains resistant to linezolid and cell lysis, while linezolid increases the cell wall thickness of the strains resistant to fosfomycin. In the Galleria mellonella infection model, the survival rate of the antibiotic combined was improved compared with that of the single drug. There was a good correlation between in vivo efficacy and in vitro susceptibility.Conclusion: The type of interaction expressed in the test combination was highly dependent on fosfomycin resistance.Keywords: linezolid, fosfomycin, interaction, resistant, Staphylococcus aureus, Galleria mellonella

Enterococci, the main pathogens associated with nosocomial infections, are resistant to many common antibacterial drugs including β-lactams, aminoglycosides, etc. Combination therapy is considered an effective way to prevent bacterial resistance. Preliminary studies in our group have shown that linezolid combined with fosfomycin has synergistic or additive antibacterial activity against enterococci, while the ability of the combination to prevent resistance remains unknown. In this study, we determined mutant prevention concentration (MPC) and mutant selection window (MSW) of linezolid, fosfomycin alone and in combination including different proportions for five clinical isolates of Enterococcus and characterized the resistance mechanism for resistant mutants. The results indicated that different proportions of linezolid combined with fosfomycin had presented different MPCs and MSWs. Compared with linezolid or fosfomycin alone, the combination can restrict the enrichment of resistant mutants at a lower concentration. A rough positive correlation between the selection index (SI) of the two agents in combination and the fractional inhibitory concentration index (FICI) of the combination displayed that the smaller FICI of linezolid and fosfomycin, the more probable their MSWs were to close each other. Mutations in ribosomal proteins (L3 and L4) were the mechanisms for linezolid resistant mutants. Among the fosfomycin-resistant mutants, only two strains have detected the MurA gene mutation related to fosfomycin resistance. In conclusion, the synergistic combination of linezolid and fosfomycin closing each other’s MSW could effectively suppress the selection of enterococcus resistant mutants, suggesting that the combination may be an alternative for preventing enterococcal resistance. In this study, the resistance mechanism of fosfomycin remains to be further studied.