PINK1 Inhibits Local Protein Synthesis to Limit Transmission of Deleterious Mitochondrial DNA Mutations.

We have previously proposed that selective inheritance, the limited transmission of damaging mtDNA mutations from mother to offspring, is based on replication competition in Drosophila melanogaster. This model, which stems from our observation that wild-type mitochondria propagate much more vigorously in the fly ovary than mitochondria carrying fitness-impairing mutations, implies that germ cells recognize the fitness of individual mitochondria and selectively boost the propagation of healthy ones. Here, we demonstrate that the protein kinase PINK1 preferentially accumulates on mitochondria enriched for a deleterious mtDNA mutation. PINK1 phosphorylates Larp to inhibit protein synthesis on the mitochondrial outer membrane. Impaired local translation on defective mitochondria in turn limits the replication of their mtDNA and hence the transmission of deleterious mutations to the offspring. Our work confirms that selective inheritance occurs at the organelle level during Drosophila oogenesis and provides molecular entry points to test this model in other systems.

Interleukin-17A educated hepatic stellate cells promote hepatocellular carcinoma occurrence through fibroblast activation protein expression.

BACKGROUND: Liver cancer is typified by a complex inflammatory tumor microenvironment, where an array of cytokines and stromal cells orchestrate a milieu that significantly influences tumorigenesis. Interleukin-17A (IL-17A), a pivotal pro-inflammatory cytokine predominantly secreted by Th17 cells, is known to play a substantial role in the etiology and progression of liver cancer. However, the precise mechanism by which IL-17A engages with hepatic stellate cells (HSCs) to facilitate the development of hepatocellular carcinoma (HCC) remains to be fully elucidated. This investigation seeks to unravel the interplay between IL-17A and HSCs in the context of HCC. METHODS: An HCC model was established in male Sprague-Dawley rats using diethylnitrosamine to explore the roles of IL-17A and HSCs in HCC pathogenesis. In vivo overexpression of Il17a was achieved using adeno-associated virus. A suite of molecular techniques, including RT-qPCR, enzyme-linked immunosorbent assays, Western blotting, cell counting kit-8 assays and colony formation assays, was employed for in vitro analyses. RESULTS: The study findings indicate that IL-17A is a key mediator in HCC promotion, primarily through the activation of hepatic progenitor cells (HPCs). This pro-tumorigenic influence appears to be mediated by HSCs, rather than through a direct effect on HPCs. Notably, IL-17A-induced expression of fibroblast activation protein (FAP) in HSCs emerged as a critical factor in HCC progression. Silencing Fap in IL-17A-stimulated HSCs was observed to reverse the HCC-promoting effects of HSCs. CONCLUSIONS: The collective evidence from this study implicates the IL-17A/FAP signaling axis within HSCs as a contributor to HCC development by enhancing HPC activation. These findings bolster the potential of IL-17A as a diagnostic and preventative target for HCC, offering new avenues for therapeutic intervention.

Arabidopsis calcineurin B-like-interacting protein kinase 8 and its functional homolog in tomato negatively regulates ABA-mediated stomatal movement and drought tolerance.

Stomatal movement is critical for water transpiration, gas exchange, and responses to biotic stresses. Abscisic acid (ABA) induces stomatal closure to prevent water loss during drought. We report that Arabidopsis CIPK8 negatively regulates ABA-mediated stomatal closure and drought tolerance. CIPK8 is highly enriched in guard cells and transcriptionally induced by ABA. Functional loss of CIPK8 results in hypersensitive stomatal closure to ABA and enhanced drought tolerance. Guard cell-specific downregulation of CIPK8 mimics the phenotype of cipk8 whereas guard cell-specific expression of a constitutive active CIPK8 (CIPK8CA) has an opposite effect, suggesting a cell autonomous activity of CIPK8. CIPK8 physically interacts with CBL1 and CBL9. Functional loss of CBL1 and CBL9 mimics ABA-hypersensitive stomatal closure of cipk8 whereas abolishes the effect of CIPK8CA, indicating that CIPK8 and CBL1/CBL9 form a genetic module in ABA-responsive stomatal movement. SlCIPK7, the functional homolog of CIPK8 in tomato (Solanum lycopersicum), plays a similar role in ABA-responsive stomatal movement. Genomic editing of SlCIPK7 results in more drought-tolerant tomato, making it a good candidate for germplasm improvement.

Pan-cancer analysis of NUP155 and validation of its role in breast cancer cell proliferation, migration, and apoptosis.

NUP155 is reported to be correlated with tumor development. However, the role of NUP155 in tumor physiology and the tumor immune microenvironment (TIME) has not been previously examined. This study comprehensively investigated the expression, immunological function, and prognostic significance of NUP155 in different cancer types. Bioinformatics analysis revealed that NUP155 was upregulated in 26 types of cancer. Additionally, NUP155 upregulation was strongly correlated with advanced pathological or clinical stages and poor prognosis in several cancers. Furthermore, NUP155 was significantly and positively correlated with DNA methylation, tumor mutational burden, microsatellite instability, and stemness score in most cancers. Additionally, NUP155 was also found to be involved in TIME and closely associated with tumor infiltrating immune cells and immunoregulation-related genes. Functional enrichment analysis revealed a strong correlation between NUP155 and immunomodulatory pathways, especially antigen processing and presentation. The role of NUP155 in breast cancer has not been examined. This study, for the first time, demonstrated that NUP155 was upregulated in breast invasive carcinoma (BRCA) cells and revealed its oncogenic role in BRCA using molecular biology experiments. Thus, our study highlights the potential value of NUP155 as a biomarker in the assessment of prognostic prediction, tumor microenvironment and immunotherapeutic response in pan-cancer.

Prevention and Potential Treatment Strategies for Respiratory Syncytial Virus.

Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.

Risk assessment and pathogen profile of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy: A retrospective study.

Emergency craniotomy in patients with traumatic brain injury poses a significant risk for surgical site infections (SSIs). Understanding the risk factors and pathogenic characteristics of SSIs in this context is crucial for improving outcomes. This comprehensive retrospective analysis spanned from February 2020 to February 2023 at our institution. We included 25 patients with SSIs post-emergency craniotomy and a control group of 50 patients without SSIs. Data on various potential risk factors were collected, including demographic information, preoperative conditions, and intraoperative details. The BACT/ALERT3D Automated Bacterial Culture and Detection System was utilized for rapid bacterial pathogen identification. Statistical analyses included univariate and multivariate logistic regression to identify significant risk factors for SSIs. The study identified Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus as the most prevalent pathogens in SSIs. Significant risk factors for SSIs included the lack of preoperative antibiotic use, postoperative drainage tube placement, diabetes mellitus, and the incorporation of invasive procedures, all of which showed a significant association with SSIs in the univariate analysis. The multivariate analysis further highlighted the protective effect of preoperative antibiotics and the increased risks associated with anaemia, diabetes mellitus, postoperative drainage tube placement, and the incorporation of invasive procedures. Our research underscores the critical role of factors like insufficient preoperative antibiotics, postoperative drainage, invasive techniques, anaemia, and diabetes mellitus in elevating the risk of surgical site infections in traumatic brain injury patients undergoing emergency craniotomy. Enhanced focus on these areas is essential for improving surgical outcomes.

Discovery and Characterization of a Myxobacterial Lanthipeptide with Unique Biosynthetic Features and Anti-inflammatory Activity.

The genomes of myxobacteria harbor a variety of biosynthetic gene clusters encoding numerous secondary metabolites, including ribosomally synthesized and post-translationally modified peptides (RiPPs) with diverse chemical structures and biological activities. However, the biosynthetic potential of RiPPs from myxobacteria remains barely explored. Herein, we report a novel myxobacteria lanthipeptide myxococin identified from Myxococcus fulvus. Myxococins represent the first example of lanthipeptides, of which the characteristic multiple thioether rings are installed by employing a Class II lanthipeptide synthetase MfuM and a Class I lanthipeptide cyclase MfuC in a cascaded way. Unprecedentedly, we biochemically characterized the first M61 family aminopeptidase MfuP involved in RiPP biosynthesis, demonstrating that MfuP showed the activity of an endopeptidase activity. MfuP is leader-independent but strictly selective for the multibridge structure of myxococin A and responsible for unwrapping two rings via amide bond hydrolysis, yielding myxococin B. Furthermore, the X-ray crystal structure of MfuP and structural analysis, including active-site mutations, are reported. Finally, myxococins are evaluated to exhibit anti-inflammatory activity in lipopolysaccharide-induced macrophages without detectable cytotoxicity.

Advances in the understanding of Blattodea evolution: Insights from phylotranscriptomics and spermathecae.

Cockroaches, an ancient and diverse group of insects on earth that originated in the Carboniferous, displays a wide array of morphology or biology diversity. The spermatheca is an organ of the insect reproductive system; the diversity of spermathecae might be the adaption to different mating and sperm storage strategies. Yet a consensus about the phylogenetic relationships among the main lineages of Blattodea and the evolution of spermatheca has not been reached until now. Here we added the transcriptome data of Anaplectidae for the first time and supplemented other family level groups (such as Blaberidae, Corydiidae) to address the pending issues. Our results showed that Blattoidea was recovered as sister to Corydioidea, which was strongly supported by molecular evidence. In Blattoidea, (Lamproblattidae + Anaplectidae) + (Cryptocercidae + Termitoidae) was strongly supported by our molecular data. In Blaberoidea, Pseudophyllodromiidae and Blaberidae were recovered to be monophyletic, while Blattellidae was found to be paraphyletic with respect to Malaccina. Ectobius sylvestris + Malaccina discoidalis formed the sister group to other Blaberoidea; Blattellidae (except Malaccina discoidalis) + Nyctiboridae was found as the sister of Blaberidae. Corydiidae was recovered to be non-monophyletic due to the embedding of Nocticola sp. Our ASR analysis of spermatheca suggested that primary spermathecae were present in the common ancestor, and it transformed at least six times during the evolutionary history of Blattodea. The evolution of spermatheca could be described as a unidirectional trend: the increased size to accommodate more sperm. Furthermore, major splits within the existing genera of cockroaches occurred in the Upper Paleogene to Neogene. Our study provides strong support for the relationship among three superfamilies and offers some new insights into the phylogeny of cockroaches. Meanwhile, this study also provides basic knowledge on the evolution of spermathecae and reproductive patterns.

STK25: a viable therapeutic target for cancer treatments?

Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.

Phylogenetic analysis of Blaberoidea reveals non-monophyly of taxa and supports the creation of multiple new subfamilies.

The superfamily Blaberoidea is a highly species-rich group of cockroaches. High-level blaberoidean phylogenetics are still under debate owing to variable taxon sampling and incongruence between mitochondrial and nuclear evolution, as well as different methods used in various phylogenetic studies. We here present a phylogenetic analysis of Blaberoidea based on a dataset combining the mitochondrial genome with two nuclear markers from representatives of all recognized families within the superfamily. Our results support the monophyly of Blaberiodea, which includes Ectobiidae s.s. (=Ectobiinae), Pseudophyllodromiidae, Nyctiboridae, Blattellidae s.s. (=Blattellinae) and Blaberidae. Ectobiidae s.s. was recovered as sister to the remaining Blaberoidea in all inferences. Pseudophyllodromiidae was paraphyletic with respect to Anaplectoidea + Malaccina. Blattellidae s.s. excluding Anaplectoidea + Malaccina formed a monophyletic group that was sister to Blaberidae. Based on our results, we propose a revised classification for Blaberoidea: Anaplectoidinae subfam.nov. and Episorineuchora gen.nov., and two new combinations at species level within Pseudophyllodromiidae; Rhabdoblattellinae subfam.nov., Calolamprodinae subfam.nov., Acutirhabdoblatta gen.nov., as well as new combinations for three species within Blaberidae. Ancestral state reconstructions based on four morphological characters allow us to infer that the common ancestor of blaberoid cockroaches is likely to be a species with characteristics similar to those found in Ectobiidae, that is, front femur Type B, arolium present, abdomen with a visible gland and male genital hook on the left side.

Comparison of post-treatment recurrence between ranibizumab injection and laser photocoagulation for type 1 retinopathy of prematurity.

OBJECTIVE: To compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors. METHODS: The clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed. RESULTS: Of the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence. CONCLUSION: There is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.

Resampling-Detection-Network-Based Robust Image Watermarking against Scaling and Cutting.

Watermarking is an excellent solution to protect multimedia privacy but will be damaged by attacks such as noise adding, image filtering, compression, and especially scaling and cutting. In this paper, we propose a watermarking scheme to embed the watermark in the DWT-DCT composite transform coefficients, which is robust against normal image processing operations and geometric attacks. To make our scheme robust to scaling operations, a resampling detection network is trained to detect the scaling factor and then rescale the scaling-attacked image before watermark detection. To make our scheme robust to cutting operations, a template watermark is embedded in the Y channel to locate the cutting position. Experiments for various low- and high-resolution images reveal that our scheme has excellent performance in terms of imperceptibility and robustness.

Binaphthyl-Based Chiral Macrocyclic Hosts for the Selective Recognition of Iodide Anions.

In this study, we explorethe synthesis of binaphthyl-based chiral macrocyclic hosts for the first time. They exhibited the selective recognition abilities of iodide anions which can be favored over those of other anions (AcO-, NO3-, ClO4-, HSO4-, Br-, PF6-, H2PO4-, BF4-, and CO3F3S-), as confirmed by UV-vis, HRMS, and 1H NMR spectroscopy experiments, as well as DFT calculations. Neutral aryl C-H···anion interactions play an important role in the formation complexes. The recognition process can be observed by the naked eye.

A Benzothiadiazole-Based Self-Assembled Cage for Cadmium Detection.

A turn-on fluorescent probe, cage 1, was efficiently self-assembled by condensing 4,4'-(benzothiadiazole-4,7-diyl)dibenzaldehyde and TREN in chloroform. The formation of cage 1 was characterized and confirmed by NMR spectroscopy, mass spectrometry, and theoretical calculations. The yield of cage 1 could be controlled by tuning the reaction conditions, such as the precursor concentration. Interestingly, the addition of 10 equiv of Cd2+ relative to cage 1 could increase the fluorescence almost seven-fold. 1H NMR and fluorescence experiments indicating fluorescence enhancement may be caused by the decomposition of cage 1. Such a high selectivity toward Cd2+ implies that the cage could potentially be employed in cadmium detection.

Microtubule affinity regulating kinase 4: A promising target in the pathogenesis of atherosclerosis.

Microtubule affinity regulating kinase 4 (MARK4), an important member of the serine/threonine kinase family, regulates the phosphorylation of microtubule-associated proteins and thus modulates microtubule dynamics. In human atherosclerotic lesions, the expression of MARK4 is significantly increased. Recently, accumulating evidence suggests that MARK4 exerts a proatherogenic effect via regulation of lipid metabolism (cholesterol, fatty acid, and triglyceride), inflammation, cell cycle progression and proliferation, insulin signaling, and glucose homeostasis, white adipocyte browning, and oxidative stress. In this review, we summarize the latest findings regarding the role of MARK4 in the pathogenesis of atherosclerosis to provide a rationale for future investigation and therapeutic intervention.

Fulvivirga marina sp. nov. and Fulvivirga sediminis sp. nov., two novel Bacteroidetes isolated from the marine sediment.

Two novel, designated strains 29W222T and 2943T, were isolated from the marine sediment from Aoshan Bay, Jimo, PR China. Growth was observed at pH 6.0-8.5 (optimum, pH 7.5) for strain 29W222T, and pH 5.5-8.5 (pH 7.0) for strain 2943T. Both strains displayed growth in 0.5-6 % NaCl with an optimum at 1 % for 29W222T; 0.5 % for 2943T. Both strains grew optimally at 33 °C. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that 29W222T and 2943T represented members of the genus Fulvivirga and strain 29W222T was most closely related to Fulvivirga kasyanovii KMM 6220T (97.9 % sequence similarity) and Fulvivirga imtechensis AK7T (95.0 %), and 2943T to Fulvivirga imtechensis AK7T (95.7 %) and Fulvivirga kasyanovii KMM 6220T (94.8 %). The genomic DNA G+C contents of 29W222T and 2943T were 39.9 and 37.7 mol%, respectively. The results of chemotaxonomic analysis indicated that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acid was iso-C15 : 0 for both strains. Average nucleotide identity and average amino acid identity values between strain 29W222T and Fulvivirga kasyanovii KMM 6220T were 78.9 and 83.6 %, respectively; the corresponding values between 2943T and Fulvivirga imtechensis AK7T were 69.8 and 63.6 %, respectively. Therefore, strains 29W222T and 2943T represent to two novel species of the genus Fulvivirga, for which the names Fulvivirga marina sp. nov. (29W222T=KCTC 62848T=MCCC 1K05194T) and Fulvivirga sediminis sp. nov. (2943T=KCTC 62847T= MCCC 1K05144T) are proposed, respectively.

Detection method and instrument of interfacial debonding inside a thermal barrier coating based on fluorescence imaging.

The interfacial delamination or debonding induced by local stress concentration is one of the kernel factors leading to spalling failure of thermal barrier coatings (TBC). In this work, for the rapid and accurate characterization of the interface delamination and debonding in TBC, the detection method and instrument were investigated based on fluorescence imaging. First, based on the principle of reflection-enhanced fluorescence, an experimental method was presented to detect interfacial debondings in TBC. A coaxial fluorescence-imaging instrument was established to realize the method above. In addition, an alkaline soluble method (ASM) was presented in this work to prepare prefabricated debondings with different transverse sizes, shapes, and thicknesses, which are basically consistent with the interfacial debondings in an actual TBC structure. Through a series of experiments, this paper verified that, using the proposed method and optical instrument, the resolutions to detect internal debonding are as small as 6 µm in the thickness dimension and less than 0.3 mm in the transverse dimension.

CircRNA CircZMYM4 inhibits the growth and metastasis of lung adenocarcinoma via the miR-587/ODAM pathway.

Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.

Retracted: Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats.

Retracted on the author's request: "We would like to withdraw our manuscript. We restarted the project for further study last year, we found that the results in this study are not solid enough and need to be further explored." Reference: Zong-Qiang Wang, Dian-Hui Xiu, Gui-Feng Liu, Jin-Lan Jiang. Overexpression of Neuregulin-1 (NRG-1) Gene Contributes to Surgical Repair of Brachial Plexus Injury After Contralateral C7 Nerve Root Transfer in Rats. Med Sci Monit 2018; 24: 5779-5787; DOI: 10.12659/MSM.908144.

Development of a Non-Linear Bi-Directional Vortex-Induced Piezoelectric Energy Harvester with Magnetic Interaction.

In this study, magnetic force is introduced to the design of a bi-directional U-shaped piezoelectric energy harvester for vortex-induced vibrations. The theoretical model of the beam structure is derived based on the Euler-Bernoulli beam theory. The vortex-induced vibration and the non-linear magnetic force are modeled according to the Rayleigh oscillator and the charge model, respectively. A prototype is fabricated and tested in two orthogonal directions under vortex-induced vibrations in a wind tunnel. Up and down wind-speed sweeps are carried out to investigate the non-linear responses of the harvester. The distance between the magnets and the length of the side beams are adjusted to examine the influence of the magnetic force on the lock-in region and voltage output of the harvester. Overall, the harvester shows strong non-linearity in the horizontal excitations. After adding magnets to the system, significant improvement of the lock-in region and the peak voltage is noticed in the horizontal mode under both up and down sweeps.