Self-powered soft robot in the Mariana Trench.

The deep sea remains the largest unknown territory on Earth because it is so difficult to explore1-4. Owing to the extremely high pressure in the deep sea, rigid vessels5-7 and pressure-compensation systems8-10 are typically required to protect mechatronic systems. However, deep-sea creatures that lack bulky or heavy pressure-tolerant systems can thrive at extreme depths11-17. Here, inspired by the structure of a deep-sea snailfish15, we develop an untethered soft robot for deep-sea exploration, with onboard power, control and actuation protected from pressure by integrating electronics in a silicone matrix. This self-powered robot eliminates the requirement for any rigid vessel. To reduce shear stress at the interfaces between electronic components, we decentralize the electronics by increasing the distance between components or separating them from the printed circuit board. Careful design of the dielectric elastomer material used for the robot's flapping fins allowed the robot to be actuated successfully in a field test in the Mariana Trench down to a depth of 10,900 metres and to swim freely in the South China Sea at a depth of 3,224 metres. We validate the pressure resilience of the electronic components and soft actuators through systematic experiments and theoretical analyses. Our work highlights the potential of designing soft, lightweight devices for use in extreme conditions.

TCF-1 and LEF-1 act upstream of Th-POK to promote the CD4(+) T cell fate and interact with Runx3 to silence Cd4 in CD8(+) T cells.

The transcription factors TCF-1 and LEF-1 are essential for early T cell development, but their roles beyond the CD4(+)CD8(+) double-positive (DP) stage are unknown. By specific ablation of these factors in DP thymocytes, we demonstrated that deficiency in TCF-1 and LEF-1 diminished the output of CD4(+) T cells and redirected CD4(+) T cells to a CD8(+) T cell fate. The role of TCF-1 and LEF-1 in the CD4-versus-CD8 lineage 'choice' was mediated in part by direct positive regulation of the transcription factor Th-POK. Furthermore, loss of TCF-1 and LEF-1 unexpectedly caused derepression of CD4 expression in T cells committed to the CD8(+) lineage without affecting the expression of Runx transcription factors. Instead, TCF-1 physically interacted with Runx3 to cooperatively silence Cd4. Thus, TCF-1 and LEF-1 adopted distinct genetic 'wiring' to promote the CD4(+) T cell fate and establish CD8(+) T cell identity.

The strong metal-support interactions induced electrocatalytic three-electron oxygen reduction to hydroxyl radicals for water treatment.

As a promising environmental remediation technology, the electro-Fenton (EF) process is mainly limited by the two rate-limiting steps, which are H2O2 generation and activation. The electrocatalytic three-electron oxygen reduction reaction (3e- ORR) can directly activate oxygen to hydroxyl radicals (•OH), which is expected to break through the rate-limiting steps of the EF process. However, limited success has been achieved in the design of 3e- ORR electrocatalysts. Herein, we propose Cu/CoSe2/C with the strong metal-support interactions to enhance the 3e- ORR process, exhibiting remarkable reactivity and stability for •OH generation. Both experiment and DFT calculation results reveal that CoSe2 is conducive to the generation of H2O2. Meanwhile, the metallic Cu can enhance the adsorption strength of *H2O2 intermediates and thus promotes the one-electron reduction to •OH. The Cu/CoSe2/C catalyst exhibits the electron-transfer number close to 3.0 during the ORR process, and exhibits the outstanding •OH generation performance, achieving a higher apparent rate constant (6.0 times faster) toward ciprofloxacin compared with its analogy without the SMSI effect. Our work represents that the SMSI effect endows Cu/CoSe2/C high activity and selectivity for •OH generation, providing a unique perspective for the design of a high-efficiency 3e- ORR catalyst.

Platelet-mediated circulating tumor cell evasion from natural killer cell killing through immune checkpoint CD155-TIGIT.

BACKGROUND AND AIMS: Circulating tumor cells (CTCs) are precursors of cancer metastasis. However, how CTCs evade immunosurveillance during hematogenous dissemination remains unclear. APPROACH AND RESULTS: We identified CTC-platelet adhesions by single-cell RNA sequencing and multiplex immunofluorescence of blood samples from multiple cancer types. Clinically, CTC-platelet aggregates were associated with significantly shorter progression-free survival and overall survival in patients with HCC. In vitro, ex vivo, and in vivo assays demonstrated direct platelet adhesions gifted cancer cells with an evasive ability from NK cell killing by upregulating inhibitory checkpoint CD155 (PVR cell adhesion molecule), therefore facilitating distant metastasis. Mechanistically, CD155 was transcriptionally regulated by the FAK/JNK/c-Jun cascade in a platelet contact-dependent manner. Further competition assays and cytotoxicity experiments revealed that CD155 on CTCs inhibited NK-cell cytotoxicity only by engaging with immune receptor TIGIT, but not CD96 and DNAM1, another 2 receptors for CD155. Interrupting the CD155-TIGIT interactions with a TIGIT antibody restored NK-cell immunosurveillance on CTCs and markedly attenuated tumor metastasis. CONCLUSIONS: Our results demonstrated CTC evasion from NK-cell-mediated innate immunosurveillance mainly through immune checkpoint CD155-TIGIT, potentially offering an immunotherapeutic strategy for eradicating CTCs.

STRN3 promotes tumour growth in hepatocellular carcinoma by inhibiting the hippo pathway.

HCC is a globally high-incidence malignant tumour, and its pathogenesis is still unclear. Recently, STRN3 has been found to be elevated in various tumours, but its expression and biological functions in HCC have not been studied. In the study, clinical correlation analysis was performed on 371 liver cancer patients from TCGA database and liver cancer tissues and normal tissues from the GEO database. qRT-PCR and western blotting were used to detect relevant proteins in cells, and CCK8 and colony formation experiments were performed to analyse cell proliferation ability. Transwell and wound healing experiments were performed to detect cell invasion ability, and flow cytometry was used to detect cell apoptosis. Single-cell sequencing data and multiple immunofluorescence were analysed for the expression abundance and distribution of certain proteins. Immunohistochemistry was used to assess the expression of STRN3 in patients' tumour and adjacent non-cancerous tissues. The results indicated STRN3 was highly expressed in liver tumour tissues and was closely associated with poor prognosis. Knockdown of STRN3 could significantly inhibit cell proliferation and migration ability. At the same time, we found that STRN3 could inhibit the Hippo pathway and promote the entry of YAP protein into the nucleus. Our study first found that STRN3 could promote tumour growth by inhibiting the Hippo pathway. The study of STRN3 can promote the understanding and treatment of the occurrence and development of HCC.

Identification of a DNA damage repair-related LncRNA signature for predicting the prognosis and immunotherapy response of hepatocellular carcinoma.

BACKGROUND: DNA damage repair (DDR) may affect tumorigenesis and therapeutic response in hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) can regulate DDR and play a vital role in maintaining genomic stability in cancers. Here, we identified a DDR-related prognostic signature in HCC and explored its potential clinical value. METHODS: Data of HCC samples were obtained from the Cancer Genome Atlas (TCGA), and a list of DDR-related genes was extracted from the Molecular Signatures database (MSigDB). A DDR-related lncRNAs signature associated to overall survival (OS) was constructed using the least absolute shrinkage and selection operator-cox regression, and was further validated by the Kaplan-Meier curve and receiver operating characteristic curve. A nomogram integrating other clinical risk factors was established. Moreover, the relationships between the signature with somatic mutation, immune landscape and drug sensitivity were explored. RESULTS: The prognostic model of 5 DDR-related lncRNAs was constructed and classified patients into two risk groups at median cut-off. The low-risk group had a better OS, and the signature was an independent prognostic indicator in HCC. A nomogram of the signature combined with TNM stage was constructed. TP53 gene was more frequently mutated in the high-risk group. Marked differences in immune cells were observed, such as CD4 + T cells, NK cells and macrophages, between the two groups. Moreover, an increase in the expression of immune checkpoint molecules was found in the high-risk group. The low-risk group presented with a significantly higher response to sorafenib or cisplatin. Finally, potential value of this signature was validated in real-world HCC patients. CONCLUSION: Our findings provided a promising insight into DDR-related lncRNAs in HCC and a personalized prediction tool for prognosis and therapeutic response.

Phylogenetic Comparative Analysis of Single-Cell Transcriptomes Reveals Constrained Accumulation of Gene Expression Heterogeneity during Clonal Expansion.

In the same way that a phylogeny summarizes the evolutionary history of species, a cell lineage tree describes the process of clonal expansion, in which gene expression differences between cells naturally accrue as a result of stochastic partitioning and imperfect expression control. How is functional homeostasis, a key factor in the biological function of any population of cells, maintained in the face of such continuous accumulation of transcriptomic heterogeneity remains largely unresolved. To answer this question, we experimentally determined the single-cell transcriptomes and lineage relationships of up to 50% cells in single-HEK293-seeded colonies. Phylogenetic comparative analyses of the single-cell transcriptomes on the cell lineage tree revealed three lines of evidence for the constrained accumulation of transcriptome heterogeneity among cells, including rapid saturation of transcriptomic heterogeneity upon four cell divisions, reduced expression differences within subtrees closer to expression boundaries, and cofluctuations among genes. Our analyses showcased the applicability of phylogenetic comparative methods in cell lineage trees, demonstrated the constrained accumulation of transcriptomic heterogeneity, and provided novel insight into the functional homeostasis of cell populations.

Th17 Cell-Derived Amphiregulin Promotes Colitis-Associated Intestinal Fibrosis Through Activation of mTOR and MEK in Intestinal Myofibroblasts.

BACKGROUND & AIMS: Intestinal fibrosis is a significant complication of Crohn's disease (CD). Gut microbiota reactive Th17 cells are crucial in the pathogenesis of CD; however, how Th17 cells induce intestinal fibrosis is still not completely understood. METHODS: In this study, T-cell transfer model with wild-type (WT) and Areg-/- Th17 cells and dextran sulfate sodium (DSS)-induced chronic colitis model in WT and Areg-/- mice were used. CD4+ T-cell expression of AREG was determined by quantitative reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of AREG on proliferation/migration/collagen expression in human intestinal myofibroblasts was determined. AREG expression was assessed in healthy controls and patients with CD with or without intestinal fibrosis. RESULTS: Although Th1 and Th17 cells induced intestinal inflammation at similar levels when transferred into Tcrßxδ-/- mice, Th17 cells induced more severe intestinal fibrosis. Th17 cells expressed higher levels of AREG than Th1 cells. Areg-/- mice developed less severe intestinal fibrosis compared with WT mice on DSS insults. Transfer of Areg-/- Th17 cells induced less severe fibrosis in Tcrßxδ-/- mice compared with WT Th17 cells. Interleukin (IL)6 and IL21 promoted AREG expression in Th17 cells by activating Stat3. Stat3 inhibitor suppressed Th17-induced intestinal fibrosis. AREG promoted human intestinal myofibroblast proliferation, motility, and collagen I expression, which was mediated by activating mammalian target of rapamycin and MEK. AREG expression was increased in intestinal CD4+ T cells in fibrotic sites compared with nonfibrotic sites from patients with CD. CONCLUSIONS: These findings reveal that Th17-derived AREG promotes intestinal fibrotic responses in experimental colitis and human patients with CD. Thereby, AREG might serve as a potential therapeutic target for fibrosis in CD.

ZmELF6-ZmPRR37 module regulates maize flowering and salt response.

The control of flowering time in maize is crucial for reproductive success and yield, and it can be influenced by environmental stresses. Using the approaches of Ac/Ds transposon and transposable element amplicon sequencing techniques, we identified a Ds insertion mutant in the ZmPRR37 gene. The Ds insertion showed a significant correlation with days to anthesis. Further research indicated that ZmPRR37-CR knockout mutants exhibited early flowering, whereas ZmPRR37-overexpression lines displayed delayed flowering compared to WT under long-day (LD) conditions. We demonstrated that ZmPRR37 repressed the expression of ZmNF-YC2 and ZmNF-YA3 to delay flowering. Association analysis revealed a significant correlation between flowering time and a SNP2071-C/T located upstream of ZmPRR37. The SNP2071-C/T impacted the binding capacity of ZmELF6 to the promoter of ZmPRR37. ZmELF6 also acted as a flowering suppressor in maize under LD conditions. Notably, our study unveiled that ZmPRR37 can enhance salt stress tolerance in maize by directly regulating the expression of ABA-responsive gene ZmDhn1. ZmDhn1 negatively regulated maize salt stress resistance. In summary, our findings proposed a novel pathway for regulating photoperiodic flowering and responding to salt stress based on ZmPRR37 in maize, providing novel insights into the integration of abiotic stress signals into floral pathways.

Risk Factors of Distant Metastatic Parathyroid Carcinoma and Insights into Therapeutic Perspectives.

BACKGROUND: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

ZmABF4-ZmVIL2/ZmFIP37 module enhances drought tolerance in maize seedlings.

Drought, as a primary environmental factor, imposes significant constraints on developmental processes and productivity of plants. PHDs were identified as stress-responsive genes in a wide range of eukaryotes. However, the regulatory mechanisms governing PHD genes in maize under abiotic stress conditions are still largely unknown and require further investigation. Here, we identified a mutant, zmvil2, in the EMS mutant library with a C to T mutation in the exon of the Zm00001d053875 (VIN3-like protein 2, ZmVIL2), resulting in premature termination of protein coding. ZmVIL2 belongs to PHD protein family. Compared to WT, zmvil2 mutant exhibited increased sensitivity to drought stress. Consistently, overexpression of ZmVIL2 enhances drought resistance in maize. Y2H, BiFC, and Co-IP experiments revealed that ZmVIL2 directly interacts with ZmFIP37 (FKBP12-interacting protein of 37). zmfip37 knockout mutants also exhibit decreased drought tolerance. Interestingly, we demonstrated that ZmABF4 directly binds to the ZmVIL2 promoter to enhance its activity in yeast one hybrid (Y1H), electrophoretic mobility shift assay (EMSA) and dual luciferase reporter assays. Therefore, we uncovered a novel model ZmABF4-ZmVIL2/ZmFIP37 that promotes drought tolerance in maize. Overall, these findings have enriched the knowledge of the functions of PHD genes in maize and provides genetic resources for breeding stress-tolerant maize varieties.

ZmC2H2-149 negatively regulates drought tolerance by repressing ZmHSD1 in maize.

Drought is a major abiotic stress that limits maize production worldwide. Therefore, it is of great importance to improve drought tolerance in crop plants for sustainable agriculture. In this study, we examined the roles of Cys2 /His2 zinc-finger-proteins (C2H2-ZFPs) in maize's drought tolerance as C2H2-ZFPs have been implicated for plant stress tolerance. By subjecting 150 Ac/Ds mutant lines to drought stress, we successfully identified a Ds-insertion mutant, zmc2h2-149, which shows increased tolerance to drought stress. Overexpression of ZmC2H2-149 in maize led to a decrease in both drought tolerance and crop yield. DAP-Seq, RNA-Seq, Y1H and LUC assays additionally showed that ZmC2H2-149 directly suppresses the expression of a positive drought tolerance regulator, ZmHSD1 (hydroxysteroid dehydrogenase 1). Consistently, the zmhsd1 mutants exhibited decreased drought tolerance and grain yield under water deficit conditions compared to their respective wild-type plants. Our findings thus demonstrated that ZmC2H2-149 can regulate ZmHSD1 for drought stress tolerance in maize, offering valuable theoretical and genetic resources for maize breeding programmes that aim for improving drought tolerance.

Photocatalyst-Free Visible Light-Induced C(sp2)-H Arylation of Quinoxalin-2(1H)-ones and Coumarins.

Herein, we describe a visible light-induced C(sp2)-H arylation method for quinoxalin-2(1H)-ones and coumarins using iodonium ylides without the need for external photocatalysts. The protocol demonstrates a broad substrate scope, enabling the arylation of diverse heterocycles through a simple and mild procedure. Furthermore, the photochemical reaction showcases its applicability in the efficient synthesis of biologically active molecules. Computational investigations at the CASPT2//CASSCF/PCM level of theory revealed that the excited state of quinoxalin-2(1H)-one facilitates electron transfer from its π bond to the antibonding orbital of the C-I bond in the iodonium ylide, ultimately leading to the formation of an aryl radical, which subsequently participates in the C-H arylation process. In addition, our calculations reveal that during the single-electron transfer (SET) process, the C-I bond cleavage in iodonium ylide and new C-C bond formation between resultant aryl radical and cationic quinoxaline species take place in a concerned manner. This enables the arylation reaction to efficiently proceed along an energy-efficient route.

Proficiency testing of diagnosis in histopathology and immunohistochemistry of breast pathology in China: results from a pilot work of National Single Disease Quality Control Program for breast cancer.

AIM: Pathologists are currently supposed to be aware of both domestic and international guidelines for breast cancer diagnosis, but it is unclear how successfully these guidelines have been integrated into routine clinical practice in China. Thus, this national proficiency testing (PT) scheme for breast pathology was set up to conduct a baseline assessment of the diagnostic capability of pathologists in China. METHODS: This national PT plan is designed and implemented according to the "Conformity assessment-General requirements for proficiency testing" (GB/T27043-2012/ISO/IEC 17043:2010). Five cases of breast cancer with six key items, including histologic type, grade, ER, PR, HER2, and Ki67, were selected for testing among 96 participants. The final PT results were published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927/cn/col22/362 ). RESULTS: Our study demonstrated that the median PT score was 89.5 (54-100). Two institutions with scores < 67 were deemed unacceptable. The accuracy of histologic type, ER, PR, HER2, and Ki67 was satisfactory (all > 86%). However, the histologic grade showed low accuracy (74.0%). The unacceptable results mainly included incorrect evaluation of histologic grade (36.7%), inaccurate evaluation of ER/PR/HER2/Ki67 (28.2%), incorrect identification of C-AD as IBC-NST (15.7%), inappropriate use of 1+/2+/3+ rather than staining percentage for ER/PR (6.1%), misclassification of ER/PR < 1% weak expression as positive staining (1.4%), and no evaluation of histologic grade in ILC, MC, and IMC (5.8%). CONCLUSIONS: our nationwide PT program exhibited a satisfactory baseline assessment of the diagnostic capability of pathologists in China. More importantly, we identify some areas for further improvement.

Chromosomal mapping of a major genetic locus from Agropyron cristatum chromosome 6P that influences grain number and spikelet number in wheat.

KEY MESSAGE: A novel locus on Agropyron cristatum chromosome 6P that increases grain number and spikelet number was identified in wheat-A. cristatum derivatives and across 3 years. Agropyron cristatum (2n = 4x = 28, PPPP), which has the characteristics of high yield with multiple flowers and spikelets, is a promising gene donor for wheat high-yield improvement. Identifying the genetic loci and genes that regulate yield could elucidate the genetic variations in yield-related traits and provide novel gene sources and insights for high-yield wheat breeding. In this study, cytological analysis and molecular marker analysis revealed that del10a and del31a were wheat-A. cristatum chromosome 6P deletion lines. Notably, del10a carried a segment of the full 6PS and 6PL bin (1-13), while del31a carried a segment of the full 6PS and 6PL bin (1-8). The agronomic characterization and genetic population analysis confirmed that the 6PL bin (9-13) brought about an increase in grain number per spike (average increase of 10.43 grains) and spikelet number per spike (average increase of 3.67) over the three growing seasons. Furthermore, through resequencing, a multiple grain number locus was mapped to the physical interval of 593.03-713.89 Mb on chromosome 6P of A. cristatum Z559. The RNA-seq analysis revealed the expression of 537 genes in the del10a young spike tissue, with the annotation indicating that 16 of these genes were associated with grain number and spikelet number. Finally, a total of ten A. cristatum-specific molecular markers were developed for this interval. In summary, this study presents novel genetic material that is useful for high-yield wheat breeding initiatives to meet the challenge of global food security through enhanced agricultural production.

Optimizing of a suitable protocol for isolating tissue-derived extracellular vesicles and profiling small RNA patterns in hepatocellular carcinoma.

BACKGROUND: Extracellular vesicles (EVs) facilitate cell-cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive. METHODS: To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis. RESULTS: A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9+ and CD63+ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895-1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming. CONCLUSION: The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.

Long-term outcomes prediction in diabetic heart failure with preserved ejection fraction by cardiac MRI.

OBJECTIVES: We aimed to explore imaging features including tissue characterization and myocardial deformation in diabetic heart failure with preserved ejection fraction (HFpEF) patients by magnetic resonance imaging (MRI) and investigate its prognostic value for adverse outcomes. MATERIALS AND METHODS: Patients with HFpEF who underwent cardiac MRI between January 2010 and December 2016 were enrolled. Feature-tracking (FT) analysis and myocardial fibrosis were assessed by cardiac MRI. Cox proportional regression analysis was performed to determine the association between MRI variables and primary outcomes. Primary outcomes were all-cause death or heart failure hospitalization during the follow-up period. RESULTS: Of the 335 enrolled patients with HFpEF, 191 had diabetes mellitus (DM) (mean age: 58.7 years ± 10.8; 137 men). During a median follow-up of 10.2 years, 91 diabetic HFpEF and 56 non-diabetic HFpEF patients experienced primary outcomes. DM was a significant predictor of worse prognosis in HFpEF. In diabetic HFpEF, the addition of conventional imaging variables (left ventricular ejection fraction, left atrial volume index, extent of late gadolinium enhancement (LGE)) and global longitudinal strain (GLS) resulted in a significant increase in the area under the receiver operating characteristic curve (from 0.693 to 0.760, p < 0.05). After adjustment for multiple clinical and imaging variables, each 1% worsening in GLS was associated with a 9.8% increased risk of adverse events (p = 0.004). CONCLUSIONS: Diabetic HFpEF is characterized by more severely impaired strains and myocardial fibrosis, which is identified as a high-risk HFpEF phenotype. In diabetic HFpEF, comprehensive cardiac MRI provides incremental value in predicting prognosis. Particularly, MRI-FT measurement of GLS is an independent predictor of adverse outcome in diabetic HFpEF. CLINICAL RELEVANCE STATEMENT: Our findings suggested that MRI-derived variables, especially global longitudinal strain, played a crucial role in risk stratification and predicting worse prognosis in diabetic heart failure with preserved ejection fraction, which could assist in identifying high-risk patients and guiding therapeutic decision-making. KEY POINTS: • Limited data are available on the cardiac MRI features of diabetic heart failure with preserved ejection fraction, including myocardial deformation and tissue characterization, as well as their incremental prognostic value. • Diabetic heart failure with preserved ejection fraction patients was characterized by more impaired strains and myocardial fibrosis. Comprehensive MRI, including tissue characterization and global longitudinal strain, provided incremental value for risk prediction. • MRI served as a valuable tool for identifying high-risk patients and guiding clinical management in diabetic heart failure with preserved ejection fraction.

Visible-Light-Promoted C3-Sulfenylindoles with Arylsulfonyl Chlorides via Electron Donor-Acceptor Complex.

In this study, we present an efficient approach for the synthesis of 3-sulfenyl indoles through an electron donor-acceptor (EDA) complex-promoted photoreaction. This sulfenylation reaction leverages sulfonyl chlorides as the sulfur source and employs PPh3 as the reductant without the need for any transition-metal catalyst or photocatalyst. At the same time, the relaxation process of the excited EDA complex was theoretically investigated at the method and multiconfiguration second-order perturbation//complete active space self-consistent field/PCM level of theory, which involves the π bond of indoles injecting an electron to the antibonding orbital of the S-Cl bond in arylsulfonyl chlorides.

Heterogeneous Photocatalytic Ring Expansion of Cyclic Ketones for the Construction of Medium-Sized Lactams.

Construction of medium-sized ring compounds remains challenging in synthetic chemistry. Herein, we describe the synthesis of medium-sized lactams via a photoinduced ring expansion of benzo-fused cyclic ketones using graphitic carbon nitride (g-C3N4) as a photocatalyst. The ring expansion protocol provided an efficient access to 8-10-membered lactams in good yields and displayed good tolerance to a range of functional groups. The mechanism studies revealed that the photochemical reaction proceeds via an intermediary of a nitrogen radical, which is generated through an oxidative hydrogen atom transfer (HAT) process.

CACNA1B protects naked mole-rat hippocampal neuron from apoptosis via altering the subcellular localization of Nrf2 after 60Co irradiation.

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation-induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next-generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation-induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation.