The RNA phosphatase PIR-1 regulates endogenous small RNA pathways in C. elegans.

Eukaryotic cells regulate 5'-triphosphorylated RNAs (ppp-RNAs) to promote cellular functions and prevent recognition by antiviral RNA sensors. For example, RNA capping enzymes possess triphosphatase domains that remove the γ phosphates of ppp-RNAs during RNA capping. Members of the closely related PIR-1 (phosphatase that interacts with RNA and ribonucleoprotein particle 1) family of RNA polyphosphatases remove both the ß and γ phosphates from ppp-RNAs. Here, we show that C. elegans PIR-1 dephosphorylates ppp-RNAs made by cellular RNA-dependent RNA polymerases (RdRPs) and is required for the maturation of 26G-RNAs, Dicer-dependent small RNAs that regulate thousands of genes during spermatogenesis and embryogenesis. PIR-1 also regulates the CSR-1 22G-RNA pathway and has critical functions in both somatic and germline development. Our findings suggest that PIR-1 modulates both Dicer-dependent and Dicer-independent Argonaute pathways and provide insight into how cells and viruses use a conserved RNA phosphatase to regulate and respond to ppp-RNA species.

Suppressive stroma-immune prognostic signature impedes immunotherapy in ovarian cancer and can be reversed by PDGFRB inhibitors.

BACKGROUND: As the most lethal gynecologic cancer, ovarian cancer (OV) holds the potential of being immunotherapy-responsive. However, only modest therapeutic effects have been achieved by immunotherapies such as immune checkpoint blockade. This study aims to propose a generalized stroma-immune prognostic signature (SIPS) to identify OV patients who may benefit from immunotherapy. METHODS: The 2097 OV patients included in the study were significant with high-grade serous ovarian cancer in the III/IV stage. The 470 immune-related signatures were collected and analyzed by the Cox regression and Lasso algorithm to generalize a credible SIPS. Correlations between the SIPS signature and tumor microenvironment were further analyzed. The critical immunosuppressive role of stroma indicated by the SIPS was further validated by targeting the major suppressive stroma component (CAFs, Cancer-associated fibroblasts) in vitro and in vivo. With four machine-learning methods predicting tumor immune subtypes, the stroma-immune signature was upgraded to a 23-gene signature. RESULTS: The SIPS effectively discriminated the high-risk individuals in the training and validating cohorts, where the high SIPS succeeded in predicting worse survival in several immunotherapy cohorts. The SIPS signature was positively correlated with stroma components, especially CAFs and immunosuppressive cells in the tumor microenvironment, indicating the critical suppressive stroma-immune network. The combination of CAFs' marker PDGFRB inhibitors and frontline PARP inhibitors substantially inhibited tumor growth and promoted the survival of OV-bearing mice. The stroma-immune signature was upgraded to a 23-gene signature to improve clinical utility. Several drug types that suppress stroma-immune signatures, such as EGFR inhibitors, could be candidates for potential immunotherapeutic combinations in ovarian cancer. CONCLUSIONS: The stroma-immune signature could efficiently predict the immunotherapeutic sensitivity of OV patients. Immunotherapy and auxiliary drugs targeting stroma could enhance immunotherapeutic efficacy in ovarian cancer.

Influenza A virus utilizes noncanonical cap-snatching to diversify its mRNA/ncRNA.

Influenza A virus (IAV) utilizes cap-snatching to obtain host capped small RNAs for priming viral mRNA synthesis, generating capped hybrid mRNAs for translation. Previous studies have been focusing on canonical cap-snatching, which occurs at the very 5' end of viral mRNAs. Here we discovered noncanonical cap-snatching, which generates capped hybrid mRNAs/noncoding RNAs mapped to the region ∼300 nucleotides (nt) upstream of each mRNA 3' end, and to the 5' region, primarily starting at the second nt, of each virion RNAs (vRNA). Like canonical cap-snatching, noncanonical cap-snatching utilizes a base-pairing between the last nt G of host capped RNAs and a nt C of template RNAs to prime RNA synthesis. However, the nt upstream of this template C is usually A/U rather than just U; prime-realignment occurs less frequently. We also demonstrate that IAV can snatch capped IAV RNAs in addition to host RNAs. Noncanonical cap-snatching likely generates novel mRNAs with start AUG encoded in viral or host RNAs. These findings expand our understanding of cap-snatching mechanisms and suggest that IAV may utilize noncanonical cap-snatching to diversify its mRNAs/ncRNAs.

A convenient strategy to clone small RNA and mRNA for high-throughput sequencing.

High-throughput sequencing has become a standard tool for analyzing RNA and DNA. This method usually needs a cDNA/DNA library ligated with specific 5' and 3' linkers. Unlike mRNA, small RNA often contains modifications including 5' cap or triphosphate and 2'-O-methyl, requiring additional processing steps before linker additions during cloning processes; due to low expression levels, it is difficult to clone small RNA with a small amount of total RNA. Here we present a new strategy to clone 5' modified or unmodified small RNA in an all-liquid-based reaction carried out in a single PCR tube with as little as 20 ng total RNA. The 7-h cloning process only needs ∼1 h of labor. Moreover, this method can also clone mRNA, simplifying the need to prepare two cloning systems for small RNA and mRNA; the barcoded PCR primers are also compatible with non-cDNA cloning applications, including the preparation of genomic libraries. Not only is our method more convenient for cloning modified RNA than available methods, but it is also more sensitive, versatile, and cost-effective. Moreover, the all-liquid-based reaction can be performed in an automated manner.

A regulatory network driving shoot lignification in rapidly growing bamboo.

Woody bamboo is environmentally friendly, abundant, and an alternative to conventional timber. Degree of lignification and lignin content and deposition affect timber properties. However, the lignification regulatory network in monocots is poorly understood. To elucidate the regulatory mechanism of lignification in moso bamboo (Phyllostachys edulis), we conducted integrated analyses using transcriptome, small RNA, and degradome sequencing followed by experimental verification. The lignification degree and lignin content increased with increased bamboo shoot height, whereas phenylalanine ammonia-lyase and Laccase activities first increased and then decreased with shoot growth. Moreover, we identified 11,504 differentially expressed genes (DEGs) in different portions of the 13th internodes of different height shoots; most DEGs associated with cell wall and lignin biosynthesis were upregulated, whereas some DEGs related to cell growth were downregulated. We identified a total of 1,502 miRNAs, of which 687 were differentially expressed. Additionally, in silico and degradome analyses indicated that 5,756 genes were targeted by 691 miRNAs. We constructed a regulatory network of lignification, including 11 miRNAs, 22 transcription factors, and 36 enzyme genes, in moso bamboo. Furthermore, PeLAC20 overexpression increased lignin content in transgenic Arabidopsis (Arabidopsis thaliana) plants. Finally, we proposed a reliable miRNA-mediated "MYB-PeLAC20" module for lignin monomer polymerization. Our findings provide definite insights into the genetic regulation of bamboo lignification. In addition to providing a platform for understanding related mechanisms in other monocots, these insights could be used to develop strategies to improve bamboo timber properties.

Axonal mRNA localization and translation: local events with broad roles.

Messenger RNA (mRNA) can be transported and targeted to different subcellular compartments and locally translated. Local translation is an evolutionally conserved mechanism that in mammals, provides an important tool to exquisitely regulate the subcellular proteome in different cell types, including neurons. Local translation in axons is involved in processes such as neuronal development, function, plasticity, and diseases. Here, we summarize the current progress on axonal mRNA transport and translation. We focus on the regulatory mechanisms governing how mRNAs are transported to axons and how they are locally translated in axons. We discuss the roles of axonally synthesized proteins, which either function locally in axons, or are retrogradely trafficked back to soma to achieve neuron-wide gene regulation. We also examine local translation in neurological diseases. Finally, we give a critical perspective on the remaining questions that could be answered to uncover the fundamental rules governing local translation, and discuss how this could lead to new therapeutic targets for neurological diseases.

YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA.

5-Methylcytosine is found in both DNA and RNA; although its functions in DNA are well established, the exact role of 5-methylcytidine (m5C) in RNA remains poorly defined. Here we identified, by employing a quantitative proteomics method, multiple candidate recognition proteins of m5C in RNA, including several YTH domain-containing family (YTHDF) proteins. We showed that YTHDF2 could bind directly to m5C in RNA, albeit at a lower affinity than that toward N6-methyladenosine (m6A) in RNA, and this binding involves Trp432, a conserved residue located in the hydrophobic pocket of YTHDF2 that is also required for m6A recognition. RNA bisulfite sequencing results revealed that, after CRISPR-Cas9-mediated knockout of the YTHDF2 gene, the majority of m5C sites in rRNA (rRNA) exhibited substantially augmented levels of methylation. Moreover, we found that YTHDF2 is involved in pre-rRNA processing in cells. Together, our data expanded the functions of the YTHDF2 protein in post-transcriptional regulations of RNA and provided novel insights into the functions of m5C in RNA biology.

Genome-wide analysis of laccase genes in moso bamboo highlights PeLAC10 involved in lignin biosynthesis and in response to abiotic stresses.

KEY MESSAGE: Twenty-three PeLACs have been identified in moso bamboo, overexpression of PeLAC10 increases the lignin content and confers drought and phenolic acid tolerance in transgenic Arabidopsis. Laccases (LACs) have multifunction involved in the processes of cell elongation, lignification and stress response in plants. However, the function of laccases in bamboo remain unclear. Here, a total of 23 laccase genes (PeLAC1-PeLAC23) were identified in moso bamboo (Phyllostachys edulis). The diverse gene structure and expression pattern of PeLACs suggested that their function should be spatiotemporal and complicated, which was supported by the expression profiles in different tissues of moso bamboo. Eighteen PeLACs were identified as the targets of ped-miR397. The putative ped-miR397-binding site in the coding region of PeLAC10 was further confirmed by RLM-5' RACE, indicating that PeLAC10 was regulated by ped-miR397 after transcription. With the increasing shoot height, the expression abundance of PeLAC10 was up-regulated and reached the maximum in 15 cm shoots, while that of ped-miR397 was relative lower and showed the minimum in 15 cm shoots. PeLAC10 was up-regulated obviously under both ABA (100 µmol L-1) and NaCl (400 mmol L-1) treatments, and it was down-regulated under the GA3 (100 µmol L-1) treatment. The transgenic Arabidopsis plants over-expressing PeLAC10 became slightly smaller and their petioles were shorter than those of Col-0. However, they had a stronger capacity in resistance to phenolic acids and drought besides higher lignin content in stems. These results indicated that overexpression of PeLAC10 was helpful to increase the content of lignin in transgenic Arabidopsis and improve the adaptability to phenolic acid and drought stresses.

Expression and functional analysis of two PsbS genes in bamboo (Phyllostachys edulis).

Higher plants have an array of photoprotection mechanisms alleviating the harmful effects of light. Non-photochemical quenching (NPQ) is one of the photoprotective mechanisms, which dissipates the excess of light energy absorbed in the light-harvesting complexes (LHCs) into thermal energy. The photosystem II subunit S (PsbS), a member of the LHC family thought to be present exclusively in higher plants, is supposed to activate NPQ through interactions with antenna proteins. However, the roles of PsbS in bamboo remain unclear. Here, two genes of bamboo (Phyllostachys edulis), PePsbS1 and PePsbS2, are investigated and functionally analyzed. PePsbS1 and PePsbS2 have a similar gene structure with three introns separated by two exons, which encode 269 and 268 amino acid residues, respectively. Tissue-specific analysis showed that PePsbS1 and PePsbS2 are highly expressed in leaf blade. Besides, they are both upregulated in the leaf blade when plantlets are submitted to an increased and prolonged light intensity, suggesting that they are light-induced. Western blot analysis indicated that the accumulation level of total PePsbSs is consistent with what obtained by quantitative real-time polymerase chain reaction for PePsbS1 and PePsbS2. Transgenic Arabidopsis plants overexpressing PePsbS1 and PePsbS2 both displayed an enhanced photoprotection. Moreover, the expression of PePsbS1 and PePsbS2 could both rescue the NPQ of Arabidopsis npq4 mutant, indicating that the PsbSs are functionally conserved between monocots and dicots. These results indicated that both PePsbS1 and PePsbS2 could circumvent photoinhibition and enhance photoprotection, which are key factors for bamboo's adaptation to different light environment.

The bamboo aquaporin gene PeTIP4;1-1 confers drought and salinity tolerance in transgenic Arabidopsis.

KEY MESSAGE: PeTIP4;1-1, an aquaporin gene involved in bamboo shoot growth, is regulated by abiotic stresses. Overexpression of PeTIP4;1-1 confers drought and salinity tolerance in transgenic Arabidopsis. Aquaporins play a central role in numerous physiological processes throughout plant growth and development. PeTIP4;1-1, an aquaporin gene isolated from moso bamboo (Phyllostachys edulis), comprises an open reading frame (ORF) of 756 bp encoding a peptide of 251 amino acids. The genomic sequence corresponding to the ORF of PeTIP4;1-1 was 1777 bp and contained three exons separated by two introns. PeTIP4;1-1 was constitutively expressed at the highest level in culms, and the expression level was elevated with increasing height of the bamboo shoot. PeTIP4;1-1 was significantly up-regulated in response to drought and salinity stresses in bamboo roots and leaves. To investigate the role of PeTIP4;1-1 in response to drought and salinity stresses, transgenic Arabidopsis plants overexpressing PeTIP4;1-1 under the control of CaMV 35S promoter were generated and subjected to morphological and physiological assays. Compared with Col-0, the transgenic plants showed enhanced tolerance to drought and salinity stresses and produced longer taproots, which had more green leaves, higher F v/F m and NPQ values, higher activities of SOD, POD and CAT, lower MDA concentration and higher water content. Transcript levels of three stress-related genes (AtP5CS, AtNHX1 and AtLEA) were enhanced. These results indicated that PeTIP4;1-1 might play an important function in response to drought and salinity stresses, and is a candidate gene for breeding of stress tolerance in other crops through genetic engineering.

Transcriptome and comparative gene expression analysis of Phyllostachys edulis in response to high light.

BACKGROUND: Photosynthesis plays a vital role as an energy source for plant metabolism, and its efficiency may be drastically reduced owing to abiotic stresses. Moso bamboo (Phyllostachys edulis), is a renewable and versatile resource with significant ecological and economic value, which encounters high light stress with large amplitude in natural environment. However, the gene expression profiles in response to high light were elusive in bamboo. RESULTS: We firstly performed physiological experiments on moso bamboo leaves treated with high light (1200 µmol · m(-2) · s(-1)). Based on the physiological results, three samples of leaves treated with high light for 0 h (CK), 0.5 h (0.5H), and 8 h (8H) were selected to perform further high-throughput RNA sequencing (RNA-Seq), respectively. Then, the transcriptomic result demonstrated that the most genes were expressed at a statistically significant value (FPKM ≥ 1) and the RNA-Seq data were validated via quantitative real time PCR. Moreover, some significant gene expression changes were detected. For instance, 154 differentially expressed genes were detected in 0.5H vs. CK, those in 8H vs. CK were 710, and 429 differentially expressed genes were also identified in 0.5H vs.8 H. Besides, 47 gene annotations closely related to photosynthesis were refined, including 35 genes annotated as light-harvesting chlorophyll a/b-binding (LHC) proteins, 9 LHC-like proteins and 3 PsbSs. Furthermore, the pathway of reactive oxygen species (ROS) in photosynthesis was further analyzed. A total of 171 genes associated with ROS-scavenging were identified. Some up-regulated transcript factors, such as NAC, WRKY, AR2/ERF, and bHLH, mainly concentrated in short-term response, while C2H2, HSF, bZIP, and MYB were largely involved in short and middle terms response to high light. CONCLUSION: Based on the gene expression analysis of moso bamboo in response to high light, we thus identified the global gene expression patterns, refined the annotations of LHC protein, LHC-like protein and PsbS, detected the pathway of ROS as well as identified ROS-scavenging genes and transcription factors in the regulation of photosynthetic and related metabolisms. These findings maybe provide a starting point to interpret the molecular mechanism of photosynthesis in moso bamboo under high light stress.

Genome-wide identification and characterization of aquaporin gene family in moso bamboo (Phyllostachys edulis).

Aquaporins (AQPs) are known to play a major role in maintaining water and hydraulic conductivity balance in the plant system. Numerous studies have showed AQPs execute multi-function throughout plant growth and development, including water transport, nitrogen, carbon, and micronutrient acquisition etc. However, little information on AQPs is known in bamboo. In this study, we present the first genome-wide identification and characterization of AQP genes in moso bamboo (Phyllostachys edulis) using bioinformatics. In total, 26 AQP genes were identified by homologous analysis, which were divided into four groups (PIPs, TIPs, NIPs, and SIPs) based on the phylogenetic analysis. All the genes were located on 26 different scaffolds respectively on basis of the gene mapped to bamboo genome. Evolutionary analysis indicated that Ph. edulis was more close to Oryza sativa than Zea mays in the genetic relationship. Besides, qRT-PCR was used to analyze gene expression profiles, which revealed that AQP genes were expressed constitutively in all the detected tissues, and were all responsive to the environmental cues such as drought, water, and NaCl stresses. This data suggested that AQPs may play fundamental roles in maintaining normal growth and development of bamboo, which would contribute to better understanding for the complex regulation mechanism involved in the fast-growing process of bamboo. Furthermore, the result could provide valuable information for further research on bamboo functional genomics.

Characterization and primary functional analysis of a bamboo NAC gene targeted by miR164b.

KEY MESSAGE: PeSNAC1 , a stress-related NAC1 from Phyllostachys edulis , was characterized. Ectopic expression in Arabidopsis indicated that PeSNAC1 together with ped -miR164b participated in the regulation of organ boundaries and stress tolerance. NAC (NAM, ATAF1/2 and CUC2) participates in many different processes regulating plant growth, development, and stress response. A total of 125 NAC genes have been predicted in moso bamboo (Phyllostachys edulis), but their roles are poorly understood. PeSNAC1 targeted by ped-miR164b was focused for further study. The cleavage of PeSNAC1 mRNA guided by ped-miR164b was validated using RLM-5' RACE. Tissue-specific expression analysis demonstrated that ped-miR164b had a declining trend from root, sheath, leaf, to that of stem, which was opposite to that of PeSNAC1. Transgenic Arabidopsis plants overexpressing either PeSNAC1 (OX-PeSNAC1) or, ped-miR164b (OX-ped-miR164b) driven by the CaMV35S promoter were generated. OX-ped-miR164b plants showed similar phenotype of cuc2 mutants whose growth was seriously suppressed. Compared with Col-0, sense OX-PeSNAC1 plants grew rapidly and flowered earlier, whereas antisense plants grew slowly and exhibited delayed flowering. Sense OX-PeSNAC1 plants had the greatest number of lateral roots, while antisense OX-PeSNAC1 and OX-ped-miR164b plants had fewer lateral roots than Col-0. Under NaCl and PEG6000 stresses, survival rates were higher and F v/F m values declined more slowly in sense OX-PeSNAC1 plants than in Col-0, with lower survival rates and a more rapid decrease in F v/F m values conversely observed in antisense OX-PeSNAC1 and OX-ped-miR164b plants. These findings indicated that ped-miR164b-targeted PeSNAC1 may play key roles in plant development and tolerance to salinity and drought stresses.

Association of a functional RAD52 genetic variant locating in a miRNA binding site with risk of HBV-related hepatocellular carcinoma.

As an important member in homologous recombination repair, RAD52 plays a crucial part in maintaining genomic stability and prevent carcinogenesis. Several cancer susceptibility RAD52 single nucleotide polymorphisms (SNPs) have been identified previously. However, little or nothing has been known about the RAD52 SNPs and their functional significance in hepatitis B viruses (HBV)-related hepatocellular carcinoma (HCC). Therefore, we investigated the association between five RAD52 SNPs (rs1051669, rs10774474, rs11571378, rs7963551, and rs6489769) and HBV-related HCC risk as well as its biological function in vivo. Genotypes were determined in two independent case-control sets from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. The allele-specific regulation on RAD52 expression by the functional genetic variant was examined with normal liver tissues. We found that only the RAD52 rs7963551 SNP was significantly associated with HCC risk, with the odds of having the rs7963551 CC genotype in patients was 0.59 (95% CI = 0.45-0.78, P = 1.5 × 10(-4), HCC cases versus chronic HBV carriers) or 0.65 (95% CI = 0.52-0.81, P = 1.1 × 10(-4), HCC cases versus healthy controls) compared with the AA genotype. In the genotype-phenotype correlation analyses of 44 human liver tissue samples, rs7963551 CC or AC was associated with a statistically significant increase of RAD52 mRNA expression, which are consistent to functional relevance of allelic regulation of RAD52 expression by rs7963551 SNP and miRNA let-7 in cancer cells. Our data demonstrated that RAD52 functional rs7963551 SNP contributes to susceptibility to developing HCC.

The ALDH7A1 genetic polymorphisms contribute to development of esophageal squamous cell carcinoma.

Although the entire etiology of esophageal squamous cell carcinoma (ESCC) is still unclear, alcohol drinking has been identified as a major environmental risk factor. The aldehyde dehydrogenase (ALDH) superfamily members are major enzymes involved in the alcohol-metabolizing pathways. Accumulating evidences demonstrated that ALDH7A1, one of ALDH superfamily members, degrades and detoxifies acetaldehyde generated by alcohol metabolism and have been associated with development and prognosis of multiple cancers. However, it is still unknown if ALDH7A1 single nucleotide polymorphisms (SNPs) contribute to ESCC susceptibility. In this study, we examined the association between sixteen ALDH7A1 SNPs and risk of developing ESCC. Genotypes were determined in 2,098 ESCC patients and 2,150 controls (three independent hospital-based case-control sets from different regions of China). Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated by logistic regression. Our data demonstrated that only the ALDH7A1 rs13182402 SNP confer susceptibility to ESCC (For AG genotype, OR = 0.75, 95 % CI = 0.66-0.91, P = 4.8 × 10(-6); for GG genotype, OR = 0.59, 95 % CI = 0.41-0.88, P = 0.003). These results are consistent to the biological functions of ALDH7A1 during alcohol metabolism and carcinogenesis.

TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer.

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis.

Ferroptosis, an iron-dependent lipid peroxidation-driven programmed cell death, is closely related to cancer therapy. The development of druggable ferroptosis inducers and their rational application in cancer therapy are critical. Here, we identified Tubastatin A, an HDAC6 inhibitor as a novel druggable ferroptosis inducer through large-scale drug screening. Tubastatin A directly bonded to GPX4 and inhibited GPX4 enzymatic activity through biotin-linked Tubastatin A putdown and LC/MS analysis, which is independent of its inhibition of HDAC6. In addition, our results showed that radiotherapy not only activated Nrf2-mediated GPX4 transcription but also inhibited lysosome-mediated GPX4 degradation, subsequently inducing ferroptosis tolerance and radioresistance in cancer cells. Tubastatin A overcame ferroptosis resistance and radioresistance of cancer cells by inhibiting GPX4 enzymatic activity. More importantly, Tubastatin A has excellent bioavailability, as demonstrated by its ability to significantly promote radiotherapy-induced lipid peroxidation and tumour suppression in a mouse xenograft model. Our findings identify a novel druggable ferroptosis inducer, Tubastatin A, which enhances radiotherapy-mediated antitumor effects. This work provides a compelling rationale for the clinical evaluation of Tubastatin A, especially in combination with radiotherapy.

Multi-slice spiral CT findings of tubulovillous adenoma of the duodenum.

OBJECTIVES: To analyze the appearance of duodenal tubulovillous adenoma on multi-slice spiral CT images to facilitate early diagnosis and treatment to potentially improve prognosis. METHODS: We retrospectively analyzed clinical data and CT imaging findings of 11 cases of duodenal tubulovillous adenomas, all confirmed by pathology. The location, size, shape, CT density, relationship with surrounding structures, accompanying bile duct obstruction, and enhancement pattern of each lesion were documented. RESULTS: All 11 lesions occurred in the descending part of the duodenum. Ten cases occurred in the duodenal papilla area. Nine cases had a low-density ring sign or semicircle sign between the lesion and the adjacent normal intestinal wall on axial images. Eight cases had differing degrees of bile duct dilatation, five of which had concomitant pancreatic duct dilatation. Noncontrast images revealed uniform soft tissue density; contrast enhanced images showed moderate, mostly uniform enhancement, with the most enhancement in the venous phase. In the arterial phase, two lesions showed linear enhancing vessels. CONCLUSIONS: On multi-slice spiral CT imaging, duodenal tubulovillous adenomas have certain characteristics that could be used for clinical diagnosis and treatment. PRECIS: On multi-slice spiral CT imaging of duodenal tubulovillous adenoma, findings of nodular or cauliflower-like shape, uniform density, uniform moderate enhancement, and a peripheral low-density ring sign could improve diagnostic accuracy.

Development of stretchable metallic glass electrodes.

Stretchable electrodes are essential components for wearable electronics. However, the stretchability of the electrodes is often achieved with the sacrifice of electronic conductivity along with huge variation in resistance. In this work, stretchable metallic glass electrodes (MG-electrodes) that have both high electronic conductivity and excellent electronic stability are developed. The stretchability of the MG-electrode is significantly improved by shrinking MG films deposited on substrates with pre-strain. We demonstrate two types of MG-electrodes. One is a transparent MG-electrode for uniaxial stretching, and the other with better conductivity is for biaxial stretching. Compared with previous electrodes, the MG-electrodes exhibit a combination of high conductivity and negligible resistivity change (<5%), making them promising candidates for interconnections. Along with the excellent corrosion resistance of metallic glasses, the electrodes may be used in harsh environments.