Editorial: Microorganisms and their derivatives for cancer therapy

[Execerpt] Cancer remains an unsolved and challenging problem. In 1890, Dr. William Bradley Coley attempted to use a mixture of dead microbes to treat cancers (Dobosz and Dzieciatkowski, 2019; Liu et al., 2022), establishing the foundation of bacteria-mediated cancer therapy. Given the recent advances in the study of the human microbiome that revealed its crucial role in tumorigenesis, development, therapy, and prognostic evaluation, additional research efforts on cancer microbial therapies have been conducted (Kurtz et al., 2019; Feng et al., 2022), with new findings supporting the potential role of bacteriolytic therapy in cancer. Our Special Research Topic aimed at exploring the trends and recent advances on the use of microorganisms and their derivatives for cancer therapy, on new anticancer agents, new genetic engineering techniques, and synthetic or new identified bacteria, which could be used for cancer monotherapy or adjuvant therapy, as well as understanding the mechanisms underlying their anticancer effects. [...]We appreciate the editorial staff and the contributors who made the Special Research Topic possible. We acknowledge the support by the National Natural Science Foundation of China (Grant Nos. 81971726, 32101218) and the State Key Laboratory of Oncogenes and Related Genes (No. KF2111).info:eu-repo/semantics/publishedVersio

L dwarfs detection from SDSS images using improved Faster R-CNN

We present a data-driven approach to automatically detect L dwarfs from Sloan Digital Sky Survey(SDSS) images using an improved Faster R-CNN framework based on deep learning. The established L dwarf automatic detection (LDAD) model distinguishes L dwarfs from other celestial objects and backgrounds in SDSS field images by learning the features of 387 SDSS images containing L dwarfs. Applying the LDAD model to the SDSS images containing 93 labeled L dwarfs in the test set, we successfully detected 83 known L dwarfs with a recall rate of 89.25% for known L dwarfs. Several techniques are implemented in the LDAD model to improve its detection performance for L dwarfs,including the deep residual network and the feature pyramid network. As a result, the LDAD model outperforms the model of the original Faster R-CNN, whose recall rate of known L dwarfs is 80.65% for the same test set. The LDAD model was applied to detect L dwarfs from a larger validation set including 843 labeled L dwarfs, resulting in a recall rate of 94.42% for known L dwarfs. The newly identified candidates include L dwarfs, late M and T dwarfs, which were estimated from color (i-z) and spectral type relation. The contamination rates for the test candidates and validation candidates are 8.60% and 9.27%, respectively. The detection results indicate that our model is effective to search for L dwarfs from astronomical images.Comment: 12 pages, 10 figures, accepted to be published in A

Comparison of the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of ventilator-associated pneumonia caused by carbapenem-resistant gram-negative bacteria: a retrospective cohort study

Objective: To investigate the clinical efficacy and toxicity of nebulized polymyxin monotherapy and combined intravenous and nebulized polymyxin for the treatment of VAP caused by CR-GNB. Additionally, among patients treated with nebulized polymyxin monotherapy, we compared the clinical efficacy and toxicity of polymyxin B and polymyxin E.Methods: This study was a single-center, retrospective study. Included patients received aerosolized polymyxin for at least 72 h with or without intravenous polymyxin for the management of CR-GNB VAP. The primary endpoint was clinical cure at the end of polymyxin therapy. Secondary endpoints included AKI incidence, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, and all-cause ICU mortality.Results: 39 patients treated with nebulized polymyxin monotherapy were assigned to the NL-polymyxin group. 39 patients treated with nebulized polymyxin combined with intravenous use of polymyxin were assigned to the IV-NL-polymyxin group. Among the NL-polymyxin group, 19 patients were treated with polymyxin B and 20 with polymyxin E. The clinical baseline characteristics before admission to the ICU and before nebulization of polymyxin were similar between the two groups. No differences were found between the two study groups in terms of microorganism distribution, VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU and all-cause ICU mortality. Similarly, survival analysis did not differ between the two groups (χ2 = 3.539, p = 0.06). AKI incidence was higher in the IV-NL-polymyxin group. When comparing the clinical efficacy and toxicity to polymyxin B and polymyxin E, there was no difference between the two groups in terms of VAP cure rate, time of bacteria-negative conversion, duration of MV after inclusion, length of stay in ICU, SOFA score, CPIS, AKI incidence and all-cause ICU mortality.Conclusion: Our study found that nebulized polymyxin monotherapy was non-inferior to combination therapy with intravenous polymyxin in treating CR-GNB-VAP. Furthermore, we observed no differences in clinical efficacy or related toxic side effects between polymyxin B and polymyxin E during nebulized polymyxin therapy as monotherapy. However, future prospective studies with larger sample sizes are required to confirm these findings

The Threshold Pion-Photoproduction of Nucleons In The Chiral Quark Model

In this paper, we show that the low energy theorem (LET) of the threshold pion-photoproduction can be fully recovered in the quark model. An essential result of this investigation is that the quark-pion operators are obtained from the effective chiral Lagrangian, and the low energy theorem does not require the constraints on the internal structures of the nucleon. The pseudoscalar quark-pion coupling generates an additional term at order $\mu=m_{\pi}/M$ only in the isospin amplitude $A^{(-)}$. The role of the transitions between the nucleon and the resonance $P_{33}(1232)$ and P-wave baryons are also discussed, we find that the leading contributions to the isospin amplitudes at $O(\mu^2)$ are from the transition between the P-wave baryons and the nucleon and the charge radius of the nucleon. The leading contribution from the P-wave baryons only affects the neutral pion production, and improve the agreement with data significantly. The transition between the resonance $P_{33}(1232)$ and the nucleon only gives an order $\mu^3$ corrections to $A^{(-)}$

A membrane-depolarizing toxin substrate of the Staphylococcus aureus type VII secretion system mediates intraspecies competition.

The type VII protein secretion system (T7SS) is conserved across Staphylococcus aureus strains and plays important roles in virulence and interbacterial competition. To date, only one T7SS substrate protein, encoded in a subset of S. aureus genomes, has been functionally characterized. Here, using an unbiased proteomic approach, we identify TspA as a further T7SS substrate. TspA is encoded distantly from the T7SS gene cluster and is found across all S. aureus strains as well as in Listeria and Enterococci. Heterologous expression of TspA from S. aureus strain RN6390 indicates its C-terminal domain is toxic when targeted to the Escherichia coli periplasm and that it depolarizes the cytoplasmic membrane. The membrane-depolarizing activity is alleviated by coproduction of the membrane-bound TsaI immunity protein, which is encoded adjacent to tspA on the S. aureus chromosome. Using a zebrafish hindbrain ventricle infection model, we demonstrate that the T7SS of strain RN6390 promotes bacterial replication in vivo, and deletion of tspA leads to increased bacterial clearance. The toxin domain of TspA is highly polymorphic and S. aureus strains encode multiple tsaI homologs at the tspA locus, suggestive of additional roles in intraspecies competition. In agreement, we demonstrate TspA-dependent growth inhibition of RN6390 by strain COL in the zebrafish infection model that is alleviated by the presence of TsaI homologs

Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti-Inflammatory Activity

Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781-1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives

Bacteria-Based Microdevices for the Oral Delivery of Macromolecules

The oral delivery of macromolecules is quite challenging due to environmental insults and biological barriers encountered along the gastrointestinal (GI) tract. Benefiting from their living characteristics, diverse bacterial species have been engineered as intelligent platforms to deliver various therapeutics. To tackle difficulties in oral delivery, innovative bacteria-based microdevices have been developed by virtue of advancements in synthetic biology and nanotechnology, with aims to overcome the instability and short half-life of macromolecules in the GI tract. In this review, we summarize the main classes of macromolecules that are produced and delivered through the oral ingestion of bacteria and bacterial derivatives. Furtherly, we discuss the engineering strategies and biomedical applications of these living microdevices in disease diagnosis, bioimaging, and treatment. Finally, we highlight the advantages as well as the limitations of these engineered bacteria used as platforms for the oral delivery of macromolecules and also propose their potential for clinical translation. The results summarized in this review article would contribute to the invention of next-generation bacteria-based systems for the oral delivery of macromolecules

Comparison of two techniques for toric intraocular lens implantation: hydroimplantation versus ophthalmic viscosurgical devices

Abstract Background To compare the results between hydroimplantation of a single-piece, acrylic foldable toric intraocular lens (IOLs) and conventional implantation using an ophthalmic viscosurgical device (OVD). Methods In this study, 60 eyes with cataract and preexisting regular corneal astigmatism of 1.0 to 3.0 diopters (D) underwent the implantation of the AcrySof toric IOLs (Alcon Laboratories, Inc.). The patients were randomly assigned to a conventional implantation technique with an OVD or a hydroimplantation technique. Comparison of preoperative and postoperative parameters was performed using paired Student t tests, and independent Student t test was used to compare between the two groups. Results Three months postoperatively, the mean subjective astigmatism was 0.45 D ± 0.24 (SD) in the OVD group and 0.49 ± 0.29 D in the hydroimplantation group (P = 0.492). The mean endothelial cell density (ECD) loss was 7.54% ± 0.82% and 7.32% ± 0.59%, respectively (P = 0.117). The mean absolute IOL rotation was 4.77 ± 2.32 degrees and 4.70 ± 1.95 degrees, respectively (P = 0.334). The mean time for IOL implantation was 71.50 ± 8.10 s and 37.60 ± 3.90 s, respectively (P  0.05), although IOP two hours postoperatively seemed to be a little higher in the OVD group. Conclusions Compared with the use of OVDs for toric IOLs implantation, the hydroimplantation technique provided advantages of increased efficiency, reduced surgical time and cost, and no concerns of OVD-induced elevated IOP. Trial registration Current Controlled Trials ISRCTN55696872, Retrospectively registered (Date of registration: 25 March 2018)

Mechanical Properties and Failure Mechanism of Granite with Maximum Free Water Absorption under Triaxial Compression

Granite in underground water-sealed storage caverns has usually been immersed for a long time. The immersion affects the mechanical properties and failure mechanism of granite with maximum free water absorption; therefore, it is crucial to study the behavior of granite under different confining pressures for engineering construction. A triaxial compression test with maximum free water absorption was conducted on granite and its mechanical properties were analyzed. A fracture scanning electron microscope test was carried out to analyze the microstructural characteristics and reveal the failure mechanism. The test results showed that the differential stress-axial strain curve can be divided into the initial compaction stage, the elastic deformation stage, the plastic deformation stage, and the post-peak strain-softening stage. With an increase in confining pressure, the duration of the initial compaction stage decreased, while the plastic deformation stage and the peak strength and peak strain stages increased. For the confining pressure range of 0–20 MPa, the peak stress difference of granite with maximum free water absorption was between 146.0 and 307.6 MPa. The elastic modulus was between 31.36 and 44.18 GPa. The cohesion (c) of the rock sample studied was 26.84 MPa and the internal friction angle (φ) was 51°. The failure mechanism of granite is tensile–shear composite failure, predominantly with tensile failure under low confining pressure regimes, and the inclined fracture surface is mainly due to shear failure under high confining pressure conditions. These research results provide updated reference data for rock engineering involving granitic mechanical properties and failure mechanisms in submerged caverns