Perceptually Inspired C0-Continuity Haptic Shape Display with Trichamber Soft Actuators.

Shape display devices composed of actuation pixels enable dynamic rendering of surface morphological features, which have important roles in virtual reality and metaverse applications. The traditional pin-array solution produces sidestep-like structures between neighboring pins and normally relies on high-density pins to obtain curved surfaces. It remains a challenge to achieve continuous curved surfaces using a small number of actuated units. To address the challenge, we resort to the concept of surface continuity in computational geometry and develop a C0-continuity shape display device with trichamber fiber-reinforced soft actuators. Each trichamber unit produces three-dimensional (3D) deformation consisting of elongation, pitch, and yaw rotation, thus ensuring rendered surface continuity using low-resolution actuation units. Inspired by human tactile discrimination threshold on height and angle gradients between adjacent units, we proposed the mathematical criteria of C0-continuity shape display and compared the maximal number of distinguishable shapes using the proposed device in comparison with typical pin-array. We then established a shape control model considering the nonlinearity of soft materials to characterize and control the soft device to display C0-continuity shapes. Experimental results showed that the proposed device with nine trichamber units could render typical sets of distinguishable C0-continuity shape sequence changes. We envision that the concept of C0-continuity shape display with 3D deformation capability could improve the fidelity of the rendered shapes in many metaverse scenarios such as touching human organs in medical palpation simulations.

Radical Addition-Enabled C-C σ-Bond Cleavage/Reconstruction to Access Functional Indanones: Total Synthesis of Carexane L.

C-C σ-bond cleavage and reconstruction is a significant tool for structural modification in synthetic chemistry but it remains a formidable challenge to perform on unstrained skeletons. Herein, we describe a radical addition-enabled C-C σ-bond cleavage/reconstruction reaction of unstrained allyl ketones to access various functional indanones bearing a benzylic quaternary center. The synthetic utility of this method has been showcased by the first total synthesis of carexane L, an indanone-based natural product.

The road less taken: Dihydroflavonol 4-reductase inactivation and delphinidin anthocyanin loss underpins a natural intraspecific flower colour variation.

Visual cues are of critical importance for the attraction of animal pollinators, however, little is known about the molecular mechanisms underpinning intraspecific floral colour variation. Here, we combined comparative spectral analysis, targeted metabolite profiling, multi-tissue transcriptomics, differential gene expression, sequence analysis and functional analysis to investigate a bee-pollinated orchid species, Glossodia major with common purple- and infrequent white-flowered morphs. We found uncommon and previously unreported delphinidin-based anthocyanins responsible for the conspicuous and pollinator-perceivable colour of the purple morph and three genetic changes underpinning the loss of colour in the white morph - (1) a loss-of-function (LOF; frameshift) mutation affecting dihydroflavonol 4-reductase (DFR1) coding sequence due to a unique 4-bp insertion, (2) specific downregulation of functional DFR1 expression and (3) the unexpected discovery of chimeric Gypsy transposable element (TE)-gene (DFR) transcripts with potential consequences to the genomic stability and post-transcriptional or epigenetic regulation of DFR. This is one of few known cases where regulatory changes and LOF mutation in an anthocyanin structural gene, rather than transcription factors, are important. Furthermore, if TEs prove to be a frequent source of mutation, the interplay between environmental stress-induced TE evolution and pollinator-mediated selection for adaptive colour variation may be an overlooked mechanism maintaining floral colour polymorphism in nature.

Probiotics Pediococcus acidilactici GR-1 promotes the functional strains and remodels gut microbiota to reduce the Cr(VI) toxicity in a dual-chamber simulated intestinal system.

Numerous animal studies have demonstrated the toxicity of hexavalent chromium [Cr(VI)] and the bioremediative effects of probiotics on the composition and functions of gut microbiota. Since the precise mechanisms of Cr(VI) detoxification and its interactions with human gut microbiota were unknown, a novel dual-chamber simulated intestinal (DCSI) system was developed to maintain both the stability of the simulated system and the composition of the gut microbiota. Probiotic GR-1 was found to regulate intestinal gut microbiota, thereby reducing the toxicity of Cr(VI) within the DCSI system. The results indicate that Cr(VI) levels were reduced from 2.260 ± 0.2438 µg/g to 1.7086 ± 0.1950 µg/g in the gut microbiota cell pellet, and Cr(VI) permeability decreased from 0.5521 ± 0.1132 µg/L to 0.3681 ± 0.0178 µg/L after 48 h in simulated gut fluid. Additionally, the removal rate of 1,1-Diphenyl-2-picrylhydrazyl (DPPH), reducibility (Vitamin C), and total antioxidant capacity (T-AOC) increased by 50.83%, 31.70%, and 27.56%, respectively, following probiotic treatment. The increase in antioxidant capacity correlated with total Cr removal (P < 0.05, r from -0.80 to 0.73). 16S rRNA sequencing analysis showed that gut microbiota composition was reshaped by the addition of probiotics, which regulated the recovery of the functional gut microbiota to normal levels, rather than restoring the entire gut microbiota composition for community function. Thus, this study not only demonstrates the feasibility and stability of culturing gut microbiota but also offers a new biotechnological approach to synthesizing functional communities with functional strains for environmental risk management.

DNA-Binding with One Finger (Dof) Transcription Factor Gene Family Study Reveals Differential Stress-Responsive Transcription Factors in Contrasting Drought Tolerance Potato Species.

DNA-binding with one finger (Dof) proteins comprise a large family that play central roles in stress tolerance by regulating the expression of stress-responsive genes via the DOFCORE element or by interacting with other regulatory proteins. Although the Dof TF has been identified in a variety of species, its systemic analysis in potato (Solanum tuberosum L.) is lacking and its potential role in abiotic stress responses remains unclear. A total of 36 potential Dof genes in potato were examined at the genomic and transcriptomic levels in this work. Five phylogenetic groups can be formed from these 36 Dof proteins. An analysis of cis-acting elements revealed the potential roles of Dofs in potato development, including under numerous abiotic stress conditions. The cycling Dof factors (CDFs) might be the initial step in the abiotic stress response signaling cascade. In potato, five CDFs (StCDF1/StDof19, StCDF2/StDof4, StCDF3/StDof11, StCDF4/StDof24, and StCDF5/StDof15) were identified, which are homologs of Arabidopsis CDFs. The results revealed that these genes were engaged in a variety of abiotic reactions. Moreover, an expression analysis of StDof genes in two potato cultivars ('Long10' (drought tolerant) and 'DXY' (drought susceptible)) of contrasting tolerances under drought stress was carried out. Further, a regulatory network mediated by lncRNA and its target Dofs was established. The present study provides fundamental knowledge for further investigation of the roles of Dofs in the adaptation of potato to drought stress, aiming to provide insights into a viable strategy for crop improvement and stress-resistance breeding.

Effect of Manganese on the Strength-Toughness Relationship of Low-Carbon Copper and Nickel-Containing Hull Steel.

The influence of varying the manganese (Mn) contents of high-strength copper-containing hull steel on its microstructural evolution and mechanical properties was investigated. With increasing Mn content from 2 to 5%, the tensile strength of the steel increased by ~100 MPa, while the elongation of steel remained at ~23.5%, indicating good plasticity. However, the 2Mn sample had 128 J higher low-temperature (-84 °C) impact work than the 5Mn sample. The microstructures of different Mn steels were composed of fresh martensite (FM), ferrite/tempered martensite (F/TM), and reversed austenite (RA). The increase in Mn content markedly increased the presence of RA and intensified the work hardening caused by the transformation-induced plasticity (TRIP) effect during the tensile process. However, as the phase transformation in different Mn steels occurred in the early stage of strain and did not extend throughout the entire plastic deformation process, increasing plasticity via phase transformation was difficult. In addition, although the volume fraction of RA increased significantly in 4Mn and 5Mn steels, the stability of RA significantly decreased. The presence of numerous metastable blocks and coarse lath-like RA contributed little to low-temperature impact work and was even detrimental to toughness. The substantial fresh martensite resulting from phase transformation facilitated microcrack generation, owing to rapid volume expansion and mutual impacts, thus reducing the work required for crack formation. Additionally, the abundance of deformation twins significantly reduced the work needed for crack propagation. These combined actions significantly reduced the low-temperature toughness of 4Mn and 5Mn steels.

Evaluating the mode of action of perfluorooctanoic acid-induced liver tumors in male Sprague-Dawley rats using a toxicogenomic approach.

The mode of action (MOA) underlying perfluorooctanoic acid (PFOA)-induced liver tumors in rats is proposed to involve peroxisome proliferator-activated receptor α (PPARα) agonism. Despite clear PPARα activation evidence in rodent livers, the mechanisms driving cell growth remain elusive. Herein, we used dose-responsive apical endpoints and transcriptomic data to examine the proposed MOA. Male Sprague-Dawley rats were treated with 0, 1, 5, and 15 mg/kg PFOA for 7, 14, and 28 days via oral gavage. We showed PFOA induced hepatomegaly along with hepatocellular hypertrophy in rats. PPARα was activated in a dose-dependent manner. Toxicogenomic analysis revealed six early biomarkers (Cyp4a1, Nr1d1, Acot1, Acot2, Ehhadh, and Vnn1) in response to PPARα activation. A transient rise in hepatocellular DNA synthesis was demonstrated while Ki-67 labeling index showed no change. Transcriptomic analysis indicated no significant enrichment in pathways related to DNA synthesis, apoptosis, or the cell cycle. Key cyclins including Ccnd1, Ccnb1, Ccna2, and Ccne2 were dose-dependently suppressed by PFOA. Oxidative stress and the nuclear factor-κB signaling pathway were unaffected. Overall, evidence for PFOA-induced hepatocellular proliferation was transient within the studied timeframe. Our findings underscore the importance of considering inter-species differences and chemical-specific effects when evaluating the carcinogenic risk of PFOA in humans.

Small Molecule SHP2 Inhibitor LXQ-217 Affects Lung Cancer Cell Proliferation in Vitro and in Vivo.

BACKGROUND: SHP2 is highly expressed in a variety of cancer and has emerged as a potential target for cancer therapeutic agents. The identification of uncharged pTyr mimics is an important direction for the development of SHP2 orthosteric inhibitors. METHODS: Surface plasmon resonance analysis and cellular thermal shift assay were employed to verify the direct binding of LXQ-217 to SHP2. The inhibitory effect of LXQ-217 was characterized by linear Weaver-Burke enzyme kinetic analysis and BIOVIA Discovery Studio. The inhibition of tumor cell proliferation by LXQ-217 was characterized by cell viability assay, colony formation assays and hoechst 33258 staining. The inhibition of lung cancer proliferation in vivo was studied in nude mice after oral administration of LXQ-217. RESULTS: An electroneutral bromophenol derivative, LXQ-217, was identified as a competitive SHP2 inhibitor. LXQ-217 induced apoptosis and inhibited growth of human pulmonary epithelial cells by affecting the RAS-ERK and PI3 K-AKT signaling pathways. Long-term oral administration of LXQ-217 significantly inhibited the proliferation ability of lung cancer cells in nude mice. Moreover, mice administered LXQ-217 orally at high doses exhibited no mortality or significant changes in vital signs. CONCLUSIONS: Our findings on the uncharged orthosteric inhibitor provide a foundation for further development of a safe and effective anti-lung cancer drug.

Damping Properties of Selective Laser-Melted Medium Manganese Mn-xCu Alloy.

In this work, selective laser melting (SLM) technology was applied to directly realize the in situ synthesis of medium manganese Mn-xCu (x = 30-40 wt.%) alloys based on the blended elemental powders. The effects of heat treatment on the microstructural evolution and damping properties of the SLMed Mn-xCu alloys were investigated. The metastable miscibility gap was studied by thermodynamic modeling and microhardness measurement. The results showed that γ-(Mn, Cu) phase with dendritic arm spacing (DAS) of 0.9-1.2 µm was the main constituent phase in the as-SLMed alloys, which was one to two orders of magnitude finer than those of the as-cast samples. Aging at 400-480°C for the Mn-30%Cu or 430°C for Mn-40%Cu alloys can induce spinodal decomposition, martensitic transformation, and α-phase precipitation, whose direct evidence was provided for the first time by transmission electron microscopy and 3D atom probe tomography in the work. The miscibility gap obtained from thermodynamics calculation was basically consistent with the microhardness results for the SLMed Mn-xCu alloys. Solution and aging (SA) treatment can improve the microstructure, tensile and damping properties of the SLMed Mn-xCu alloys more obviously than aging treatment. A 2.3-2.8 and 4.3-4.5 times increase was produced in damping capacity in the aged SLMed and SLMed+SAed Mn-xCu samples, respectively.

Rab3a attenuates spinal cord injury by mediating vesicle release.

BACKGROUND: Rab3a regulates vesicle secretion and transport. Emerging evidences have shown that extracellular vesicles (EVs) can reach target lesions of injured spinal cords and exert a positive effect on these lesions. However, the molecular mechanism by which Rab3a regulates vesicle secretion to ameliorate spinal cord injury (SCI) is not fully understood. METHODS: An SCI rat model was established which was used to examine the pathological changes and Rab3a expression in spinal cord tissue. Rab3a was overexpressed in the model rats to demonstrate its effect on SCI repair. Rab3a was also knocked down in neuronal cells to verify its role in vesicle secretion and neuronal cells. The binding protein of Rab3a was identified by Co-IP and mass spectrometry. RESULTS: Rab3a was significantly downregulated in SCI rats and Rab3a overexpression promoted SCI repair. Rab3a knockdown inhibited the secretion of neuronal cell-derived EVs. Compared to the EVs from the equal number of control neuronal cells, EVs from Rab3a-knockdown neuronal cells promoted M1 macrophage polarization, which in turn, promoted neuronal cell apoptosis. Mechanistically, STXBP1 was identified as a binding protein of Rab3a, and their interaction promoted the secretion of neuronal cell-derived EVs. Furthermore, METTL2b was significantly downregulated in SCI rats, and METTL2b knockdown significantly reduced Rab3a protein expression. CONCLUSION: These results suggest that Rab3a promotes the secretion of neuronal cell-derived EVs by interacting with its binding protein STXBP1. Neuronal cells-derived EVs inhibited the polarization of M1 macrophages in the spinal cord microenvironment, thereby promoting SCI repair. Our findings provide a theoretical basis for the clinical treatment of SCI.

Photo-induced versatile aliphatic C-H functionalization via electron donor-acceptor complex.

The ability to selectively introduce diverse functionality onto hydrocarbons is of substantial value in the synthesis of both small molecules and pharmaceuticals. In this endeavour, as a photocatalyst- and metal-free process, the electron donor-acceptor (EDA) strategy has not been well explored. Here we report an approach to aliphatic carbon-hydrogen bond diversification through an EDA complex constituted by HCl and SIV=O groups. As an efficient hydrogen atom transfer (HAT) reagent, chlorine radical can be produced via a proton-coupled electron transfer process in this system. Based on this unusual path, a photo-promoted versatile aliphatic C-H functionalization is developed without photo- and metal-catalysts, including thiolation, arylation, alkynylation, and allylation. This conversion has concise and ambient reaction conditions, good functional group tolerance, and substrate diversity, and provides an alternative solution for the high value-added utilization of bulk light alkanes.

Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized. METHODS: We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS. We applied logistic and Cox proportional hazards regression to compare cases to 42,752 population-based and 948 age and sex-matched controls. Genetic information was obtained from exome and genotype array data.Results and Conclusions: We observed that NfL was 1.42-fold higher in cases vs population-based controls. At two to three years pre-diagnosis, NfL levels in patients exceeded the 95th percentile of age and sex-matched controls. A time-to-diagnosis analysis showed that a 2-fold increase in NfL levels was associated with a 3.4-fold risk of diagnosis per year, with NfL being most predictive of case status at two years (AUC = 0.96). Participants with genetic variation that might put them at risk for familial disease (N = 46) did not show a different pattern of association than those without (N = 191). DISCUSSION: Our findings show that NfL is elevated and discriminative of future ALS diagnosis up to two years prior to diagnosis in patients with and without genetic risk variants.

Basic leucine zipper gene VvbZIP61 is expressed at a quantitative trait locus for high monoterpene content in grape berries.

The widely appreciated muscat flavor of grapes and wine is mainly attributable to the monoterpenes that accumulate in ripe grape berries. To identify quantitative trait loci (QTL) for grape berry monoterpene content, an F1 mapping population was constructed by a cross between two grapevine genotypes, one with neutral aroma berries (cv. 'Beifeng') and the other with a pronounced muscat aroma (elite Vitis vinifera line '3-34'). A high-density genetic linkage map spanning 1563.7 cM was constructed using 3332 SNP markers that were assigned to 19 linkage groups. Monoterpenes were extracted from the berry of the F1 progeny, then identified and quantified by gas chromatography-mass spectrometry. Twelve stable QTLs associated with the amounts of 11 monoterpenes in berries were thus identified. In parallel, the levels of RNA in berries from 34 diverse cultivars were estimated by RNA sequencing and compared to the monoterpene content of the berries. The expression of five genes mapping to stable QTLs correlated well with the monoterpene content of berries. These genes, including the basic leucine zipper VvbZIP61 gene on chromosome 12, are therefore considered as potentially being involved in monoterpene metabolism. Overexpression of VvbZIP61 in Vitis amurensis callus through Agrobacterium-mediated transformation significantly increased the accumulation of several monoterpenes in the callus, including nerol, linalool, geranial, geraniol, ß-myrcene, and D-limonene. It is hypothesized that VvbZIP61 expression acts to increase muscat flavor in grapes. These results advance our understanding of the genetic control of monoterpene biosynthesis in grapes and provide important information for the marker-assisted selection of aroma compounds in grape breeding.

Nickel-catalyzed stereoselective reductive cross-coupling of gem-difluoroalkenes with alkenyl electrophiles.

Herein we develop a Ni-catalyzed defluorinative cross-electrophile coupling of gem-difluoroalkenes with alkenyl electrophiles that allowed the generation of C(sp2)-C(sp2) bonds. The reaction provided various monofluoro 1,3-dienes with broad functional group compatibility and excellent stereoselectivity. Synthetic transformations and applications to the modification of complex compounds were also demonstrated.

Serum vitamin D levels and Sjogren's syndrome: bi-directional Mendelian randomization analysis.

BACKGROUND: Based on the results of existing observational studies, it can be found that the association between serum vitamin D levels and the risk of Sjogren's syndrome (SS) in humans is still controversial. Based on this situation, this study aimed to assess the causal relationship between serum vitamin D levels and SS by using the Mendelian randomization (MR) approach. METHODS: In this study, genome-wide association studies (GWAS) summary statistics on serum vitamin D levels [sample size = 417,580 (UK Biobank)] and SS [sample size = 416,757 (cases = 2495, controls = 414,262) (FinnGen)] were used. The bi-directional MR analysis was then used to assess possible causal relationships. The major analysis method of MR was performed using inverse-variance weighted (IVW), supplemented by MR-Egger and the weighted median approaches. In addition, sensitivity analyses were used to ensure the stability of the results, including Cochran's Q test, MR-PRESSO, MR-Egger intercept test, and the leave-one-out test. RESULTS: The MR suggested that no significant causal effects of serum 25(OH)D levels on SS risks were observed [odds ratio (OR) = 0.9824; 95% confidence interval (CI) = 0.7130 to 1.3538; P = 0.9137]. Similarly, no evidence supported the causal effects of SS on serum vitamin D levels (ß: 0.0076, 95% CI: - 0.0031 to 0.0183; P = 0.1640). CONCLUSION: This study found no obvious evidence that serum vitamin D level is causally associated with SS risks or vice versa. We call for larger sample size studies to further unravel the potential causal relationship and the exact mechanism.

Perceptual Localization Performance of the Whole Hand Vibrotactile Funneling Illusion.

Funneling illusion refers to a midway perceived illusory tactile sensation between multiple distant stimulations. Since haptic illusion provides guidelines to simplify tactile interfaces, funneling illusion has been explored on different parts of human skin. This study aimed to evaluate the perceptual localization performance of vibrotactile funneling illusion on palmar side of the hand. It is based on the idea of leveraging the vibrotactile funneling illusion to produce distributed vibrotactile stimuli across the entire hand using only a few vibration actuators. By designing a glove with actuators on five fingertips and the palm heel, we measured the localization density of funneling illusion on the whole hand in two experimental conditions [one-dimensional (1D) illusion along each finger and 2D illusion on palmar plane]. The results showed that the average correct rate of location discrimination was 97%, 82%, and 71% in 3-, 4-, and 5-location densities for 1D illusion and 85%, 70%, and 58% in 11-, 16-, and 21-location densities for 2D illusion, respectively. These findings confirmed the feasibility of simulating multi-location stimuli using only a few actuators. Also, perceptual guidelines were provided for the designing of vibrotactile gloves by leveraging the entire hand funneling illusion.

Nationally funded health management projects for older adults in China and the United States: Comparative analysis based on data from two principal institutions.

Objectives: To systematically summarize and compare the health management projects on the aged population funded by the National Institutes of Health (NIH) in the US and the National Natural Science Foundation of China (NSFC) in China. Methods: All elderly-related projects from 2007 to 2022 were retrieved by searching the project titles, abstracts, and keywords such as "older adults," "elderly," "aged," "health management," and so on. Python, CiteSpace, and VOSviewer were used to extract, integrate, and visualize the relevant information. Results: A total of 499 NSFC projects and 242 NIH projects were retrieved. For both countries, prestigious universities and institutions received the most funded projects; the projects that got the most funds were longitudinal studies. Both countries attach great importance to investment in the health management of the aged population. However, different focuses existed in health management projects for older adults in the two countries due to distinct national conditions and development levels. Conclusions: The analysis results of this study can provide a reference for other countries with similar challenges of population aging. Effective measures should be taken to promote the transformation and implementation practice of the project achievements. Nurses can benefit from these projects and facilitate the translation of relevant research findings into clinical practice to improve nursing quality for older adults.

Learnings about Aß from human brain recommend the use of a live-neuron bioassay for the discovery of next generation Alzheimer's disease immunotherapeutics.

Despite ongoing debate, the amyloid ß-protein (Aß) remains the prime therapeutic target for the treatment of Alzheimer's disease (AD). However, rational drug design has been hampered by a lack of knowledge about neuroactive Aß. To help address this deficit, we developed live-cell imaging of iPSC-derived human neurons (iNs) to study the effects of the most disease relevant form of Aß-oligomeric assemblies (oAß) extracted from AD brain. Of ten brains studied, extracts from nine caused neuritotoxicity, and in eight cases this was abrogated by Aß immunodepletion. Here we show that activity in this bioassay agrees relatively well with disruption of hippocampal long-term potentiation, a correlate of learning and memory, and that measurement of neurotoxic oAß can be obscured by more abundant non-toxic forms of Aß. These findings indicate that the development of novel Aß targeting therapeutics may benefit from unbiased activity-based discovery. To test this principle, we directly compared 5 clinical antibodies (aducanumab, bapineuzumab,  BAN2401, gantenerumab, and SAR228810) together with an in-house aggregate-preferring antibody (1C22) and established relative EC50s in protecting human neurons from human Aß. The results yielded objective numerical data on the potency of each antibody in neutralizing human oAß neuritotoxicity. Their relative efficacies in this morphological assay were paralleled by their functional ability to rescue oAß-induced inhibition of hippocampal synaptic plasticity. This novel paradigm provides an unbiased, all-human system for selecting candidate antibodies for advancement to human immunotherapy.

A Systematic Pan-Cancer Analysis of MEIS1 in Human Tumors as Prognostic Biomarker and Immunotherapy Target.

BACKGROUND: We intended to explore the potential immunological functions and prognostic value of Myeloid Ecotropic Viral Integration Site 1 (MEIS1) across 33 cancer types. METHODS: The data were acquired from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene expression omnibus (GEO) datasets. Bioinformatics was used to excavate the potential mechanisms of MEIS1 across different cancers. RESULTS: MEIS1 was downregulated in most tumors, and it was linked to the immune infiltration level of cancer patients. MEIS1 expression was different in various immune subtypes including C2 (IFN-gamma dominant), C5 (immunologically quiet), C3 (inflammatory), C4 (lymphocyte depleted), C6 (TGF-b dominant) and C1 (wound healing) in various cancers. MEIS1 expression was correlated with Macrophages_M2, CD8+T cells, Macrophages_M1, Macrophages_M0 and neutrophils in many cancers. MEIS1 expression was negatively related to tumor mutational burden (TMB), microsatellite instability (MSI) and neoantigen (NEO) in several cancers. Low MEIS1 expression predicts poor overall survival (OS) in adrenocortical carcinoma (ACC), head and neck squamous cell carcinoma (HNSC), and kidney renal clear cell carcinoma (KIRC) patients, while high MEIS1 expression predicts poor OS in colon adenocarcinoma (COAD) and low grade glioma (LGG) patients. CONCLUSION: Our findings revealed that MEIS1 is likely to be a potential new target for immuno-oncology.

New Pyrroline Isolated from Antarctic Krill-Derived Actinomycetes Nocardiopsis sp. LX-1 Combining with Molecular Networking.

Antarctic krill (Euphausia superba) of the Euphausiidae family comprise one of the largest biomasses in the world and play a key role in the Antarctic marine ecosystem. However, the study of E. superba-derived microbes and their secondary metabolites has been limited. Chemical investigation of the secondary metabolites of the actinomycetes Nocardiopsis sp. LX-1 (in the family of Nocardiopsaceae), isolated from E. superba, combined with molecular networking, led to the identification of 16 compounds a-p (purple nodes in the molecular network) and the isolation of one new pyrroline, nocarpyrroline A (1), along with 11 known compounds 2-12. The structure of the new compound 1 was elucidated by extensive spectroscopic investigation. Compound 2 exhibited broad-spectrum antibacterial activities against A. hydrophila, D. chrysanthemi, C. terrigena, X. citri pv. malvacearum and antifungal activity against C. albicans in a conventional broth dilution assay. The positive control was ciprofloxacin with the MIC values of <0.024 µM, 0.39 µM, 0.39 µM, 0.39 µM, and 0.20 µM, respectively. Compound 1 and compounds 7, 10, and 11 displayed antifungal activities against F. fujikuroi and D. citri, respectively, in modified agar diffusion test. Prochloraz was used as positive control and showed the inhibition zone radius of 17 mm and 15 mm against F. fujikuroi and D. citri, respectively. All the annotated compounds a-p by molecular networking were first discovered from the genus Nocardiopsis. Nocarpyrroline A (1) features an unprecedented 4,5-dihydro-pyrrole-2-carbonitrile substructure, and it is the first pyrroline isolated from the genus Nocardiopsis. This study further demonstrated the guiding significance of molecular networking in the research of microbial secondary metabolites.