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Protein arginine methyltransferase 5 (PRMT5) is a master epigenetic regulator and an extensively validated therapeutic target in multiple cancers. Notably, PRMT5 is the only PRMT that requires an obligate cofactor, methylosome protein 50 (MEP50), to function. We developed compound

CO2 capture, utilization, and storage (CCUS) technology is a rare option for the large-scale use of fossil fuels in a low-carbon way, which will definitely play a part in the journey towards carbon neutrality. Within the CCUS nexus, CCU is especially interesting because these processes will establish a new “atmosphere-to-atmosphere” carbon cycle and thus indirectly offer huge potential in carbon reduction. This study focuses on the new positioning of CCUS in the carbon neutrality scenario and aims to identify potential cutting-edge/disruptive CCU technologies that may find important application opportunities during the decarbonization of the energy and industrial system. To this end, direct air capture (DAC), flexible metal-framework materials (MOFs) for CO2 capture, integrated CO2 capture and conversion (ICCC), and electrocatalytic CO2 reduction (ECR) were selected, and their general introduction, the importance to carbon neutrality, and most up-to-date research progress are summarized.

shRNA KD of SULT2B1b expression yields similar results to siRNA KD.

SULT2B1b KD reduces RWPE-1 cell viability.

Cell line authentication.

SULT2B1b expression and CS accumulation in human prostate specimens.

The Supplemental Methods give additional details for methods in the main text.

Supplementary Figure from Targeting Protein Arginine Methyltransferase 5 Suppresses Radiation-induced Neuroendocrine Differentiation and Sensitizes Prostate Cancer Cells to Radiation

Modulation of SULT2B1b alters relative abundance of CS in LNCaP cells.

Additional information for Materials and Methods section.

SULT2B1b KD in C4-2 cells induces cell death.

Figure S1 provides quality control from scRNA-seq analysis. Figure S2 indicates altered pathways in SULT2B1b KD cells. Figure S3 demonstrates TNF and SULT2B1b KD interact to further reduce AR activity in LNCaP cells. Figure S4 demonstrates that TNFR expression is not altered by SULT2B1b KD. Figure S5 demonstrates that SULT2B1b KD induces TRADD expression in LNCaP cells. Figure S6 indicates SULT2B1 is expressed at low levels. Figure S7 supports that TRAIL, TL1, and DAXX are not involved in apoptosis in SULT2B1b KD cells. Table S1 gives correlations of SULT2B1 with TNF-related genes.

Transcriptional activity of LXRα vs. LXRβ in LNCaP cells.

Supplementary Data from Targeting Protein Arginine Methyltransferase 5 Suppresses Radiation-induced Neuroendocrine Differentiation and Sensitizes Prostate Cancer Cells to Radiation

Supplementary Table from Targeting Protein Arginine Methyltransferase 5 Suppresses Radiation-induced Neuroendocrine Differentiation and Sensitizes Prostate Cancer Cells to Radiation

Clarity of Terahertz image is essential at various security checkpoints to avoid life’s dangers and treats. However, Terahertz images are distorted by noise. Noise is frequently present in digital images during the image collection, coding, delivery, and processing phases. It is extremely difficult to remove noise from digital images without prior knowledge of the noise model. Wavelet transforms have gained popularity as a tool for image denoising. In this paper, we advance a solution to this challenge using Global Threshold selection as well as wavelet transform filters. When compared to denoising Gaussian noise at the same percentage induced, biorthogonal is the most effective denoising filter for salt and pepper noise. As the salt and pepper noise increases from 20% to 60%, the hidden security image as our target varnishes or is overpowered by the induced salt and pepper noise. We discover that despite the fact that the bior 4.4 and sym4.0 wavelet transform filters prove powerful in denoising the image, it is still not clearer and that when an image is tainted by Gaussian noise, wavelet shrinkage denoising is nearly perfect in both bior4.4 and sym 4.0, whereas when the image is tainted by salt & pepper noise, wavelet shrinkage denoising is nearly perfect in both bior4.4 and sym 4.0.

Prostate cancer remains the second leading cause of cancer death among American men. Radiotherapy is a potentially curative treatment for localized prostate cancer, and failure to control localized disease contributes to the majority of prostate cancer deaths. Neuroendocrine differentiation (NED) in prostate cancer, a process by which prostate adenocarcinoma cells transdifferentiate into neuroendocrine-like (NE-like) cells, is an emerging mechanism of resistance to cancer therapies and contributes to disease progression. NED also occurs in response to treatment to promote the development of treatment-induced neuroendocrine prostate cancer (NEPC), a highly aggressive and terminal stage disease. We previously demonstrated that by mimicking clinical radiotherapy protocol, fractionated ionizing radiation (FIR) induces prostate cancer cells to undergo NED in vitro and in vivo. Here, we performed transcriptomic analysis and confirmed that FIR-induced NE-like cells share some features of clinical NEPC, suggesting that FIR-induced NED represents a clinically relevant model. Furthermore, we demonstrated that protein arginine methyltransferase 5 (PRMT5), a master epigenetic regulator of the DNA damage response and a putative oncogene in prostate cancer, along with its cofactors pICln and MEP50, mediate FIR-induced NED. Knockdown of PRMT5, pICln, or MEP50 during FIR-induced NED and sensitized prostate cancer cells to radiation. Significantly, PRMT5 knockdown in prostate cancer xenograft tumors in mice during FIR prevented NED, enhanced tumor killing, significantly reduced and delayed tumor recurrence, and prolonged overall survival. Collectively, our results demonstrate that PRMT5 promotes FIR-induced NED and suggests that targeting PRMT5 may be a novel and effective radiosensitization approach for prostate cancer radiotherapy.

In an effort to reduce resource consumption through recycling, Al2O3–Cr2O3 refractories were prepared by sintering a mixture of brown corundum and recycled aluminum chromium slag at 1600 °C. To elucidate the significance of TiO2 in refractory, the effect of TiO2 addition on the room- and high-temperature mechanical properties of these refractories was investigated. The observed stepwise progression in the high-temperature mechanical properties of the specimens was explained by considering the results of thermodynamic simulations, as well as those of phase and microstructural analyses. This behavior was ascribed to the generation of Al2TiO5 in the matrix of the specimens. Moreover, the addition of TiO2 increased the content of undecomposed Al2TiO5, and it was accompanied by the appearance of several microcracks in the matrix portion. The high temperatures caused the integration of microcracks and counteracted the thermal stresses in the specimens, which considerably improved the high-temperature mechanical properties and the thermal shock resistance.

Supplementary Figure S1 - S8

Sequences of shRNA and oligonucleotides, antibodies information, datasets information

Details for methods not included in the article file

BackgroundRadiation therapy (RT) is a standard treatment regimen for locally advanced prostate cancer; however, its failure results in tumor recurrence, metastasis, and cancer-related death. The recurrence of cancer after radiotherapy is one of the major challenges in prostate cancer treatment. Despite overall cure rate of 93.3% initially, prostate cancer relapse in 20-30% patients after radiation therapy. Cancer cells acquire radioresistance upon fractionated ionizing radiation (FIR) treatment, eventually undergo neuroendocrine differentiation (NED) and transform into neuroendocrine-like cells, a mechanism involved in acquiring resistance to radiation therapy. Radiosensitizers are agents that inhibit the repair of radiation-induced DNA damage. Protein arginine methyltransferase 5 (PRMT5) gets upregulated upon ionizing radiation treatment and epigenetically activates DNA damage repair genes in prostate cancer cells. In this study, we targeted PRMT5 with JNJ-64619178 and assessed its effect on DNA damage repair gene activation, radiosensitization, and FIR-induced NED in prostate cancer.MethodsγH2AX foci analysis was performed to evaluate the DNA damage repair after radiation therapy. RT-qPCR and western blot were carried out to analyze the expression of DNA damage repair genes. Clonogenic assay was conducted to find out the surviving fraction after radiation therapy. NED was targeted with JNJ-64619178 in androgen receptor (AR) positive and negative prostate cancer cells undergoing FIR treatment.ResultsJNJ-64619178 inhibits DNA damage repair in prostate cancer cells independent of their AR status. JNJ-64619178 impairs the repair of ionizing radiation-induced damaged DNA by transcriptionally inhibiting the DNA damage repair gene expression and radiosensitizes prostate, glioblastoma and lung cancer cell line. It targets NED induced by FIR in prostate cancer cells.ConclusionJNJ-64619178 can radiosensitize and suppress NED induced by FIR in prostate cancer cells and can be a potential radiosensitizer for prostate cancer treatment.

With the wide adoption of genomic sequencing in children having seizures, an increasing number ofSCN2Agenetic variants have been revealed as genetic causes of epilepsy. Voltage-gated sodium channel Nav1.2, encoded by geneSCN2A, is predominantly expressed in the pyramidal excitatory neurons and supports action potential (AP) firing. One recurrentSCN2Agenetic variant is L1342P, which was identified in multiple patients with epileptic encephalopathy and intractable seizures. However, the mechanism underlying L1342P-mediated seizures and the pharmacogenetics of this variant in human neurons remain unknown. To understand the core phenotypes of the L1342P variant in human neurons, we took advantage of a reference human-induced pluripotent stem cell (hiPSC) line from a male donor, in which L1342P was introduced by CRISPR/Cas9-mediated genome editing. Using patch-clamping and microelectrode array (MEA) recordings, we revealed that cortical neurons derived from hiPSCs carrying heterozygous L1342P variant have significantly increased intrinsic excitability, higher sodium current density, and enhanced bursting and synchronous network firing, suggesting hyperexcitability phenotypes. Interestingly, L1342P neuronal culture displayed a degree of resistance to the anticonvulsant medication phenytoin, which recapitulated aspects of clinical observation of patients carrying the L1342P variant. In contrast, phrixotoxin-3 (PTx3), a Nav1.2 isoform-specific blocker, can potently alleviate spontaneous and chemically-induced hyperexcitability of neurons carrying the L1342P variant. Our results reveal a possible pathogenic underpinning of Nav1.2-L1342P mediated epileptic seizures and demonstrate the utility of genome-edited hiPSCs as anin vitroplatform to advance personalized phenotyping and drug discovery.SIGNIFICANCE STATEMENTA mounting number ofSCN2Agenetic variants have been identified from patients with epilepsy, but howSCN2Avariants affect the function of human neurons contributing to seizures is still elusive. This study investigated the functional consequences of a recurringSCN2Avariant (L1342P) using human iPSC-derived neurons and revealed both intrinsic and network hyperexcitability of neurons carrying a mutant Nav1.2 channel. Importantly, this study recapitulated elements of clinical observations of drug-resistant features of the L1342P variant, and provided a platform forin vitrodrug testing. Our study sheds light on cellular mechanism of seizures resulting from a recurring Nav1.2 variant, and helps to advance personalized drug discovery to treat patients carrying pathogenicSCN2Avariant.

Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma that generally originates from Schwann cells. The prognosis for this type of malignancy is relatively poor due to complicated genetic alterations and the lack of specific targeted therapy. Chromosome fragment 4q22-23 is frequently deleted in MPNSTs and other human tumors, suggesting tumor suppressor genes may reside in this region. Here, we provide evidence that SMARCAD1, a known chromatin remodeler, is a novel tumor suppressor gene located in 4q22-23. We identified two human homologous smarcad1 genes (smarcad1a and smarcad1b) in zebrafish, and both genes share overlapping expression patterns during embryonic development. We demonstrated that two smarcad1a loss-of-function mutants, sa1299 and p403, can accelerate MPNST tumorigenesis in the tp53 mutant background, suggesting smarcad1a is a bona fide tumor suppressor gene for MPNSTs. Moreover, we found that DNA double-strand break (DSB) repair might be compromised in both mutants compared to wildtype zebrafish, as indicated by pH2AX, a DNA DSB marker. In addition, both SMARCAD1 gene knockdown and overexpression in human cells were able to inhibit tumor growth and displayed similar DSB repair responses, suggesting proper gene expression level or gene dosage is critical for cell growth. Given that mutations of SMARCAD1 sensitize cells to PARP inhibitors in yeast and the human U2OS osteosarcoma cell line, the identification of SMARCAD1 as a novel tumor suppressor gene might contribute to the development of new cancer therapies for MPNSTs. This article is protected by copyright. All rights reserved.

Metastatic and locally advanced prostate cancer is treated by pharmacological targeting of androgen synthesis and androgen response via androgen signaling inhibitors (ASI), most of which target the androgen receptor (AR). However, ASI therapy invariably fails after 1-2 years. Emerging clinical evidence indicates that in response to ASI therapy, the AR-positive prostatic adenocarcinoma can transdifferentiate into AR-negative neuroendocrine prostate cancer (NEPC) in 17-25 % treated patients, likely through a process called neuroendocrine differentiation (NED). Despite high clinical incidence, the epigenetic pathways underlying NED and ASI therapy-induced NED remain unclear. By utilizing a combinatorial single cell and bulk mRNA sequencing workflow, we demonstrate in a time-resolved manner that following AR inhibition with enzalutamide, prostate cancer cells exhibit immediate loss of canonical AR signaling activity and simultaneous morphological change from epithelial to NE-like (NEL) morphology, followed by activation of specific neuroendocrine (NE)-associated transcriptional programs. Additionally, we observed that activation of NE-associated pathways occurs prior to complete repression of epithelial or canonical AR pathways, a phenomenon also observed clinically via heterogenous AR status in clinical samples. Our model indicates that, mechanistically, ASI therapy induces NED with initial morphological change followed by deactivation of canonical AR target genes and subsequent de-repression of NE-associated target genes, while retaining AR expression and transcriptional shift towards non-canonical AR activity. Coupled with scRNA-seq and CUTRUN analysis, our model system can provide a platform for screening of potential therapeutic agents that may prevent ASI-induced NED or reverse the NED process.

The performance of a new type of concrete columns reinforced with multi-tied spiral transverse reinforcements called MTSTR columns has not yet been investigated and compared with other types of col...

Protein arginine methyltransferase 5 (PRMT5) was discovered two decades ago. The first decade focused on the biochemical characterization of PRMT5 as a regulator of many cellular processes in a healthy organism. However, over the past decade, evidence has accumulated to suggest that PRMT5 may function as an oncogene in multiple cancers via both epigenetic and non-epigenetic mechanisms. In this review, we focus on recent progress made in prostate cancer, including the role of PRMT5 in the androgen receptor (AR) expression and signaling and DNA damage response, particularly DNA double-strand break repair. We also discuss how PRMT5-interacting proteins that are considered PRMT5 cofactors may cooperate with PRMT5 to regulate PRMT5 activity and target gene expression, and how PRMT5 can interact with other epigenetic regulators implicated in prostate cancer development and progression. Finally, we suggest that targeting PRMT5 may be employed to develop multiple therapeutic approaches to enhance the treatment of prostate cancer.

Osteosarcoma (OS) is the most common bone malignancy in adolescents and has poor clinical outcomes. Protein arginine methyltransferase 5 (PRMT5) has recently been shown to be aberrantly expressed in various cancers, yet its role in OS remains elusive. Here, we found that PRMT5 was overexpressed in OS and its overexpression predicted poor clinical outcomes. PRMT5 knockdown significantly triggered pronounced senescence in OS cells, as evidenced by the increase in senescence-associated β-galactosidase (SA-β-gal)-stained cells, induction of p21 expression, and upregulation of senescence-associated secretory phenotype (SASP) gene expression. In addition, we found that PRMT5 plays a key role in regulating DNA damaging agents-induced OS cell senescence, possibly, via affecting the repair of DNA damage. Furthermore, we found that TXNIP acts as a key factor mediating PRMT5 depletion-induced DNA damage and cellular senescence. Mechanistically, TRIM21, which interacts with PRMT5, was essential for the regulation of TXNIP/p21 expression. In summary, we propose a model in which PRMT5, by interaction with TRIM21, plays a key role in regulating the TXNIP/p21 axis during senescence in OS cells. The present findings suggest that PRMT5 overexpression in OS cells might confer resistance to chemotherapy and that targeting the PRMT5/TRIM21/TXNIP signaling may enhance the therapeutic efficacy in OS.

Nitrogen and/or sulfur doped carbons were extensively investigated as CO2 adsorbents, however their performance in CO2 capture from combustion flue gas, which is the largest stationary emission source, was less promising. Herein, potassium was used as a dopant for carbon, and a new series of materials, namely potassium intercalated carbons (PICs), were prepared sequentially by oxidation of mesoporous carbon, potassium ion exchange, and calcination. Based on results from FT-IR, XPS, TG-MS, etc., it was found the pre-loaded potassium interacted with the carbon matrix during calcination, enabled great flexibility in: (1) porosity adjustment by “in-situ activation”, and (2) surface chemistry manipulation by potassium intercalation. Taking together, the optimized sample (PIC-700) showed fast and stable CO2 uptake of 5.23 wt.% in flue gas conditions (40 °C, 1 bar, 15%CO2), which is among the highest for carbon-based adsorbents. Such promising performance is directly related to the enhanced CO2 affinity due to the presence of potassium dopants. Dynamic separation of CO2 from 15%CO2/85%N2 showed similar adsorption capacity, and no performance decay could be observed during temperature swing cycles, demonstrating the great potential for the PICs for practical CO2 capture applications.

Under the low load conditions, the motor drives the compressor to increase the intake of the engine, and under the high load conditions, the motor recovers the excess exhaust energy, which greatly improves the performance of the diesel engine in all aspects. In this paper, the one-dimensional simulation prediction model of TBD620V16 diesel engine is established and checked. On this basis, the external electric auxiliary turbocharging system of motor is established. The influence of motor power on the performance of diesel engine under different working conditions is studied by simulation, and the control strategy is put forward according to the influence of power and economy of diesel engine under low load. Based on this control strategy, the improvement effect of power performance and economy under low load conditions is studied. The results show that there is an optimal motor power in each load condition to make the comprehensive thermal efficiency of diesel engine reach the maximum value. Under low load condition, with the increase of diesel engine speed, the pressure ratio of electrically assisted turbocharged diesel engine is higher and the fuel consumption is lower. When the diesel engine is accelerated from 25% to 30% load condition, the supercharged pressure of electrically assisted turbocharged diesel engine is stabilized for about 3s, and the supercharged pressure is higher when it is stable, and BSFC is significantly lower than that of traditional turbocharged diesel engine.

The structure of diffuser vanes has a significant influence on the performance of centrifugal compressors. To research the influence of diffuser vane thickness on the overall performance and internal flow condition of the centrifugal compressor. This paper takes a centrifugal compressor as the research object. By changing the diffuser vane thickness, and using three-dimensional fluid simulation technology to carry out simulation research. The results show that the thinner diffuser vanes can greatly improve the efficiency, flow rate and outlet temperature of the centrifugal compressor. For internal local fluid characteristics, thin diffuser blades have lower internal heat load. However, the local flow of fluid is not consistent with the change of vane thickness.

To improve the low accuracy of the zero-dimensional combustion model established by BP-NN, a particle swarm-neural network (PSO-NN) algorithm was proposed. The PSO optimize weights and thresholds of NN, and the operating and combustion parameters are constructed, and then compared with NN algorithm. The results show that comparing with NN algorithm, the zero-dimensional combustion model constructed by PSO-NN algorithm has higher prediction accuracy, and the mean square error of the main combustion period m is 0.0034, which is 78.21% lower than that before optimization. The particle swarm algorithm has quicker convergence and stronger versatility, which is suitable for the study of diesel engine 0-D model.

To realize zero carbon emission in internal combustion engines and boost the growth of ammonia fuel, we mixed a few hydrogens into ammonia fuel to boost the atomization and combustion performance in the combustion chamber. We study hydrogen and ammonia mixed and injected directly through two injectors, the intake temperature is 551k, to find the best injection advance angle combination to ensure the overall working performance of the ammonia Dual fuel engine. The investigation shows that when the main/auxiliary fuel injection timing is 704°CA, the knock value is less than 2, the combustion in the cylinder is gentle, and the negative work phenomenon of knock combustion is avoided. The engine power is the highest and the best economy. The emissions of soot, CO, HC, and CH2O are at a very low level, the CO2 content before and after combustion increases to zero, and the NOx emission is slightly higher than the original engine. We will improve engine NOx emission through SCR Technology in the future. The investigation results will boost the development of an ammonia and hydrogen compression ignition engine and boost the internal combustion engine to zero carbon combustion mode.

In order to study the sequential turbocharging switching process of low-speed diesel engine, this paper uses GT-power software to establish a simulation model of sequential turbocharging low-speed diesel engine. It is enhanced and improved into a model of a sequential supercharged diesel engine. Modules such as load, governor, valve control, and surge margin are set up in the simulation model. Then parameters such as switching speed, valve opening time and response time are set in the model. Through the above preparations, the thesis has carried out the simulation calculation of the sequential supercharging transient switching process and verified the rationality of the setting parameters and the accuracy of the module setting. This provides a certain reference for the valve control strategy of the sequential supercharging switching system of low-speed diesel engines.

The Global Evaluation of SARS-CoV-2/hCoV-19 Sequences 2 (GESS v2 https://shiny.ph.iu.edu/GESS_v2/) is an updated version of GESS, which has offered a handy query platform to analyze single-nucleotide variants (SNVs) on millions of high coverages and high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes provided by the Global Initiative on Sharing Avian Influenza Data (GISAID). Including the tools in the first version, the GESS v2 is embedded with new functions, which allow users to search SNVs, given the viral nucleotide or amino acid sequence. The GESS v2 helps users to identify SNVs or SARS-CoV-2 lineages enriched in countries of user’s interest and show the migration path of a selected lineage on a world map during specific time periods chosen by the users. In addition, the GESS v2 can recognize the dynamic variations of newly emerging SNVs in each month to help users monitor SNVs, which will potentially become dominant soon. More importantly, multiple sets of analyzed results about SNVs can be downloaded directly from the GESS v2 by which users can conduct their own independent research. With these significant updates, the GESS v2 will continue to serve as a public open platform for researchers to explore SARS-CoV-2 evolutionary patterns from the perspectives of the prevalence and impact of SNVs.

An RC shear wall (wall1), a composite shear wall composed of a single external steel plate connected to a concrete panel (wall2), a composite shear wall constructed from two external steel plates connected to an internal concrete panel (wall3) and finally a composite shear wall fabricated with a single internal steel plate embedded within a concrete panel (wall4) are considered in this study and their behavior are assessed and compared under the effect of an in-plane cyclic load. Variation of the three functions include shear load capacity, energy absorption and shear stiffness of the walls are evaluated numerically using the ABAQUS finite element software. The performance of numerical models is validated against to the experimental results. The effects of four parameters consisting of compressive strength of concrete, yield strength of steel plate, height-to-length ratio of the wall and the thickness of the steel plate are investigated on the above-mentioned functions. Obtained results show that the wall4 has the best performance among all four types of shear walls. For instance, the energy absorption capacity of the wall4 is approximately two times greater than that of wall1 and wall2.