Biogated mesoporous silica nanoagents for inhibition of cell migration and combined cancer therapy.

Migration is an initial step in tumor expansion and metastasis; suppressing cellular migration is beneficial to cancer therapy. Herein, we designed a novel biogated nanoagents that integrated the migration inhibitory factor into the mesoporous silica nanoparticle (MSN) drug delivery nanosystem to realize cell migratory inhibition and synergistic treatment. Antisense oligonucleotides (Anti) of microRNA-330-3p, which is positively related with cancer cell proliferation, migration, invasion, and angiogenesis, not only acted as the locker for blocking drugs but also acted as the inhibitory factor for suppressing migration via gene therapy. Synergistic with gene therapy, the biogated nanoagents (termed as MSNs-Gef-Anti) could achieve on-demand drug release based on the intracellular stimulus-recognition and effectively kill tumor cells. Experimental results synchronously demonstrated that the migration suppression ability of MSNs-Gef-Anti nanoagents (nearly 30%) significantly contributed to cancer therapy, and the lethality rate of the non-small-cell lung cancer was up to 70%. This strategy opens avenues for realizing efficacious cancer therapy and should provide an innovative way for pursuing the rational design of advanced nano-therapeutic platforms with the combination of cancer cell migratory inhibition.

Matrix metalloproteinases as attractive therapeutic targets for chronic pain: A narrative review.

Chronic pain constitutes an abnormal pain state that detrimentally affects the quality of life, daily activities, occupational performance, and stability of mood. Despite the prevalence of chronic pain, effective drugs with potent abirritation and minimal side effects remain elusive. Substantial studies have revealed aberrant activation of the matrix metalloproteinases (MMPs) in multiple chronic pain models. Additionally, emerging evidence has demonstrated that the downregulation of MMPs can alleviate chronic pain in diverse animal models, underscoring the unique and crucial role of MMPs in different stages and types of chronic pain. This review delves into the mechanistic insights and roles of MMPs in modulating chronic pain. The aberrant activation of MMPs has been linked to neuropathic pain through mechanisms involving myelin abnormalities in peripheral nerve and spinal dorsal horn (SDH), hyperexcitability of dorsal root ganglion (DRG) neurons, activation of N-methyl-d-aspartate receptors (NMDAR) and Ca2+-dependent signals, glial cell activation, and proinflammatory cytokines release. Different MMPs also contribute significantly to inflammatory pain and cancer pain. Furthermore, we summarized the substantial therapeutic potential of MMP pharmacological inhibitors across different types of chronic pain. Overall, our findings underscore the promising therapeutic prospects of MMPs targeting for managing chronic pain.

Targeting the JAK2/STAT3 signaling pathway for chronic pain.

Chronic pain is a notable health concern because of its prevalence, persistence, and associated mental stress. Drugs targeting chronic pain with potent abirritation, and minimal side effects remain unidentified. Substantial evidence indicates that the Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway plays a distinct and critical role in different stages of chronic pain. Aberrant activation of the JAK2/STAT3 signaling pathway is evident in multiple chronic pain models. Moreover, an increasing number of studies have demonstrated that the downregulation of JAK2/STAT3 can attenuate chronic pain in different animal models. In this review, we investigated the mechanism and role of the JAK2/STAT3 signaling pathway in modulating chronic pain. The aberrant activation of JAK2/STAT3 can trigger chronic pain by interacting with microglia and astrocytes, releasing proinflammatory cytokines, inhibiting anti-inflammatory cytokines, and regulating synaptic plasticity. We also retrospectively reviewed current reports on JAK2/STAT3 pharmacological inhibitors that demonstrated their significant therapeutic potential in different types of chronic pain. In summary, our results provide strong evidence that the JAK2/STAT3 signaling pathway is a promising therapeutic target for chronic pain.

Post-crotonylation oxidation by a monooxygenase promotes acetyl-CoA synthetase degradation in Streptomyces roseosporus.

Protein post-translational modifications (PTMs) with various acyl groups play central roles in Streptomyces. But whether these acyl groups can be further modified, and the influences of these potential modifications on bacterial physiology have not been addressed. Here in Streptomyces roseosporus with rich crotonylation, a luciferase monooxygenase LimB is identified to elaborately regulate the crotonylation level, morphological development and antibiotic production by oxidation on the crotonyl groups of an acetyl-CoA synthetase Acs. This chemical modification on crotonylation leads to Acs degradation via the protease ClpP1/2 pathway and lowered intracellular crotonyl-CoA pool. Thus, we show that acyl groups after PTMs can be further modified, herein named post-PTM modification (PPM), and LimB is a PTM modifier to control the substrate protein turnover for cell development of Streptomyces. These findings expand our understanding of the complexity of chemical modifications on proteins for physiological regulation, and also suggest that PPM would be widespread.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Inhibition of Structural Transformation and Surface Lattice Oxygen Activity for Excellent Stability Li-Rich Mn-Based Layered Oxides.

Li-rich Mn-based layered oxides (LLOs) are one of the most promising cathode materials, which have exceptional anionic redox activity and a capacity that surpasses 250 mA h/g. However, the change from a layered structure to a spinel structure and unstable anionic redox are accompanied by voltage attenuation, poor rate performance, and problematic capacity. The technique of stabilizing the crystal structure and reducing the surface oxygen activity is proposed in this paper. A coating layer and highly concentrated oxygen vacancies are developed on the material's surface, according to scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. In situ EIS shows that structural transformation and oxygen release are inhibited during the first charge and discharge. Optimized 3@LRMA has an average attenuation voltage of 0.55 mV per cycle (vs 1.7 mV) and a capacity retention rate of 93.4% after 200 cycles (vs 52.8%). Postmortem analysis indicates that the successful doping of Al ions into the crystal structure effectively inhibits the structural alteration of the cycling process. The addition of oxygen vacancies reduces the surface lattice's redox activity. Additionally, surface structure deterioration is successfully halted by N- and Cl-doped carbon coating. This finding highlights the significance of lowering the surface lattice oxygen activity and preventing structural alteration, and it offers a workable solution to increase the LLO stability.

Mitochondrial gene expression in different organs of Hoplobatrachus rugulosus from China and Thailand under low-temperature stress.

BACKGROUND: Hoplobatrachus rugulosus (Anura: Dicroglossidae) is distributed in China and Thailand and the former can survive substantially lower temperatures than the latter. The mitochondrial genomes of the two subspecies also differ: Chinese tiger frogs (CT frogs) display two identical ND5 genes whereas Thai tiger frogs (TT frogs) have two different ND5 genes. Metabolism of ectotherms is very sensitive to temperature change and different organs have different demands on energy metabolism at low temperatures. Therefore, we conducted studies to understand: (1) the differences in mitochondrial gene expression of tiger frogs from China (CT frogs) versus Thailand (TT frogs); (2) the differences in mitochondrial gene expression of tiger frogs (CT and TT frogs) under short term 24 h hypothermia exposure at 25 °C and 8 °C; (3) the differences in mitochondrial gene expression in three organs (brain, liver and kidney) of CT and TT frogs. RESULTS: Utilizing RT-qPCR and comparing control groups at 25 °C with low temperature groups at 8 °C, we came to the following results. (1) At the same temperature, mitochondrial gene expression was significantly different in two subspecies. The transcript levels of two identical ND5 of CT frogs were observed to decrease significantly at low temperatures (P < 0.05) whereas the two different copies of ND5 in TT frogs were not. (2) Under low temperature stress, most of the genes in the brain, liver and kidney were down-regulated (except for COI and ATP6 measured in brain and COI measured in liver of CT frogs). (3) For both CT and TT frogs, the changes in overall pattern of mitochondrial gene expression in different organs under low temperature and normal temperature was brain > liver > kidney. CONCLUSIONS: We mainly drew the following conclusions: (1) The differences in the structure and expression of the ND5 gene between CT and TT frogs could result in the different tolerances to low temperature stress. (2) At low temperatures, the transcript levels of most of mitochondrial protein-encoding genes were down-regulated, which could have a significant effect in reducing metabolic rate and supporting long term survival at low temperatures. (3) The expression pattern of mitochondrial genes in different organs was related to mitochondrial activity and mtDNA replication in different organs.

Cementless total hip arthroplasty for three different degrees of hip involved secondary to ankylosing spondylitis: an analysis of 195 hips.

BACKGROUND: Hip involved secondary to ankylosis spondylitis (AS) had a huge influence on hip function. Cementless total hip arthroplasty (THA) can improve hip function. However, no previous study compared the outcomes of THA for AS patients with three different degrees of hip involvement. METHODS: The 195 hips were retrospectively analyzed and divided into non-ankylosed group (group A, 94 hips), fibrous ankylosed group (group B, 49 hips), and bony ankylosed group (group C, 52 hips). postoperative range of motion (ROM), harris hip scores (HHS), the short-form 12 health survey (SF-12), length of stay (LOS), cost, radiological assessments, and complications were compared. RESULTS: The follow-up time was (79.4 ± 29.5) months for group A, (80.6 ± 28.9) months for group B, and (79.1 ± 28.9) months for group C (P = 0.966). Group A had the best postoperative hip ROM (P < 0.001), while group A and B can realize better HHS than group C (P < 0.001). The three groups had similar SF-12 postoperatively. For group A, LOS and cost for unilateral procedure were the least than that for group B and C (P = 0.003 and P = 0.001). Similar radiological assessments were achieved for three groups. 1 hip in group A encountered delay union of wound. 1 hip in group C encountered delay union of wound and dislocation and another patient encountered femoral fracture intraoperatively. 12 hips (12.8%) in group A, 6 hips (12.2%) in group B, and 6 hips (11.5%) in group C encountered asymptomatic heterotopic ossification (P = 0.977). CONCLUSION: For AS patients with hip involvement, THA can improve hip ROM and function. THA for the non-ankylosed hip can realize the better hip function and postoperative ROM than ankylosed hip.

Mitogenome Analysis of Four Lamiinae Species (Coleoptera: Cerambycidae) and Gene Expression Responses by Monochamus alternatus When Infected with the Parasitic Nematode, Bursaphelenchus mucronatus.

We determined the mitochondrial gene sequence of Monochamus alternatus and three other mitogenomes of Lamiinae (Insect: Coleoptera: Cerambycidae) belonging to three genera (Aulaconotus, Apriona and Paraglenea) to enrich the mitochondrial genome database of Lamiinae and further explore the phylogenetic relationships within the subfamily. Phylogenetic trees of the Lamiinae were built using the Bayesian inference (BI) and maximum likelihood (ML) methods and the monophyly of Monochamus, Anoplophora, and Batocera genera was supported. Anoplophora chinensis, An. glabripennis and Aristobia reticulator were closely related, suggesting they may also be potential vectors for the transmission of the pine wood pathogenic nematode (Bursaphelenchus xylophilus) in addition to M. alternatus, a well-known vector of pine wilt disease. There is a special symbiotic relationship between M. alternatus and Bursaphelenchus xylophilus. As the native sympatric sibling species of B. xylophilus, B. mucronatus also has a specific relationship that is often overlooked. The analysis of mitochondrial gene expression aimed to explore the effect of B. mucronatus on the energy metabolism of the respiratory chain of M. alternatus adults. Using RT-qPCR, we determined and analyzed the expression of eight mitochondrial protein-coding genes (COI, COII, COIII, ND1, ND4, ND5, ATP6, and Cty b) between M. alternatus infected by B. mucronatus and M. alternatus without the nematode. Expression of all the eight mitochondrial genes were up-regulated, particularly the ND4 and ND5 gene, which were up-regulated by 4-5-fold (p < 0.01). Since longicorn beetles have immune responses to nematodes, we believe that their relationship should not be viewed as symbiotic, but classed as parasitic.

The complete mitochondrial genome of Annamanum lunulatum (Coleoptera: Lamiinae) and its phylogeny.

The complete mitochondrial genome of the Annamanum lunulatum is 15,610 bp in length, which contains 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and the A + T-rich region. The arrangement of genes is identical to all know longhorn beetles mitochondrial genomes. The overall AT content of the mitochondrial genome is 75.3%, whereas the AT content of A + T-rich region is 84.3%. In ML and BI phylogenetic analyses, A. lunulatum is a sister clade to Blepephaeus succinctor, and the monophyly of Lamiinae is supported.

The complete mitochondrial genomes of five longicorn beetles (Coleoptera: Cerambycidae) and phylogenetic relationships within Cerambycidae.

Cerambycidae is one of the most diversified groups within Coleoptera and includes nearly 35,000 known species. The relationships at the subfamily level within Cerambycidae have not been convincingly demonstrated and the gene rearrangement of mitochondrial genomes in Cerambycidae remains unclear due to the low numbers of sequenced mitogenomes. In the present study, we determined five complete mitogenomes of Cerambycidae and investigated the phylogenetic relationship among the subfamilies of Cerambycidae based on mitogenomes. The mitogenomic arrangement of all five species was identical to the ancestral Cerambycidae type without gene rearrangement. Remarkably, however, two large intergenic spacers were detected in the mitogenome of Pterolophia sp. ZJY-2019. The origins of these intergenic spacers could be explained by the slipped-strand mispairing and duplication/random loss models. A conserved motif was found between trnS2 and nad1 gene, which was proposed to be a binding site of a transcription termination peptide. Also, tandem repeat units were identified in the A + T-rich region of all five mitogenomes. The monophyly of Lamiinae and Prioninae was strongly supported by both MrBayes and RAxML analyses based on nucleotide datasets, whereas the Cerambycinae and Lepturinae were recovered as non-monophyletic.

The complete mitochondrial genome of Mantis religiosa (Mantodea: Mantidae) from Canada and its phylogeny.

The complete mitochondrial genome of Mantis religiosa (Mantodea: Mantidae) from Canada was successfully sequenced. The mitochondrial genome was a circular molecule of 15,521 bp in length, containing 13 protein-coding genes, two rRNA genes, 23 tRNA genes (including an extra tRNAArg gene), and the control region. The AT content of the whole genome was 76.9% and the length of the control region was 636 bp with 81.9% AT content. The structure of the M. religiosa mitochondrial genome from Canada was almost identical to M. religiosa from China and their genetic distance was just 0.017. In Bayesian inference (BI) and maximum likelihood (ML) analyses, we found that M. religiosa was a sister clade to Statilia sp. and the monophyly of the genera Hierodula and Rhombodera was not supported.

The mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) from Fujian and the phylogeny of Caenidae within Ephemeroptera.

The phylogenetic relationship of Caenidae remains hotly debated within the Ephemeroptera. We sequenced the complete mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) to discuss the phylogenetic relationships among the Caenidae. The mitochondrial genome of Caenis sp. collected from Jian'ou, Fujian province, China is a circular molecule of 15,392 bp in length containing 37 genes (13 protein-coding genes, 22 tRNAs, and two rRNAs), which showed the typical insect mitochondrial gene arrangement. In BI and ML phylogenetic trees using 23 species from 13 families, the monophyly of the families Caenidae, Heptageniidae, Isonychiidae, and Vietnamellidae was strongly supported. The clade of Caenidae is a sister clade to the clade of Teloganodidae and Baetidae.

Electrospun emodin polyvinylpyrrolidone blended nanofibrous membrane: a novel medicated biomaterial for drug delivery and accelerated wound healing.

In this work, blended nanofibrous membranes were prepared by an electrospinning technique with polyvinylpyrrolidone (PVP) K90 as the filament-forming polymer, and emodin, an extract of polygonum cuspidate known as a medicinal plant, as the treatment drug. Detailed analysis of the blended nanofibrous membrane by scanning electron microscopy, Differential scanning calorimetry and X-ray diffraction revealed that emodin was well distributed in the ultrafine fibers in the form of amorphous nanosolid dispersions. Results from attenuated total reflectance Fourier transform infrared spectra suggested that the main interactions between PVP and emodin might be mediated through hydrogen bonding. In vitro dissolution tests proved that the blended nanofibrous membrane produced more desired release kinetics of the entrapped drug (emodin) as compared to the pure drug. Furthermore, wound healing test and histological evaluation revealed that the emodin loaded nanofibrous membrane to be more effective as a healing accelerator thereby proving potential strategies to develop composite drug delivery system as well as promising materials for future therapeutic biomedical applications.