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The thermal vacuum test (TVT) is an important verification process in the development of spacecraft and load. There are often multiple temperature points on the device under test (DUT) that require control. The interaction among multiple channels poses a challenge for temperature control in the TVT. To solve this problem, a multi-channel Smith proportional–integral–derivative (PID) controller based on a grouping neural network (Grouping-NN) is proposed. Firstly, the mathematical derivation for a typical multi-channel temperature control model of the TVT is carried out. Then, the multi-channel interaction system is identified using a Grouping-NN to predict the output temperature of each channel by grouping the hidden layer neurons according to the number of channels. Finally, two Grouping-NNs are utilized to update the Smith predictor, and the time-delay error is fed back to the PID controller, which is used to optimize the control effect of the multi-channel interaction system under high time delay. The proposal is compared with the traditional PID controller and Smith predictor-based PID controller through simulation. The simulation results show that the proposed method has better suppression of overshooting. In addition, the algorithm is verified by controlling the temperature of six channels in a practical thermal vacuum test. [ABSTRACT FROM AUTHOR]

Lysine-63-linked (K63-linked) polyubiquitination of TRAF3 coordinates the engagement of pattern-recognition receptors with recruited adaptor proteins and downstream activator TBK1 in pathways that induce type I IFN. Whether autoubiquitination or other E3 ligases mediate K63-linked TRAF3 polyubiquitination remains unclear. We demonstrated that mice deficient in the E3 ligase gene Hectd3 remarkably increased host defense against infection by intracellular bacteria Francisella novicida, Mycobacterium, and Listeria by limiting bacterial dissemination. In the absence of HECTD3, type I IFN response was impaired during bacterial infection both in vivo and in vitro. HECTD3 regulated type I IFN production by mediating K63-linked polyubiquitination of TRAF3 at residue K138. The catalytic domain of HECTD3 regulated TRAF3 K63 polyubiquitination, which enabled TRAF3-TBK1 complex formation. Our study offers insights into mechanisms of TRAF3 modulation and provides potential therapeutic targets against infections by intracellular bacteria and inflammatory diseases., Introduction The high prevalence of multidrug-resistant bacterial infections is a growing public health threat and can complicate further treatment, especially for infections by intracellular bacterial pathogens, which can establish an [...]

The main reason for the degradation of the underwater image is the light absorption and scattering. The images are captured in the underwater environment often have some problems such as loss of image information, low contrast, and color distortion. In order to solve the above problems, this paper proposes an image enhancement method for the underwater environment. With the help of the underwater imaging model and dark channel prior theory, a new idea of adding transmission correction and color compensation to G and B color channels is proposed. Experimental results show that, compared with the traditional methods, this method has a better effect on the underwater image with less color deviation.

Triple‐negative breast cancer (TNBC) has higher molecular heterogeneity and metastatic potential and the poorest prognosis. Because of limited therapeutics against TNBC, irradiation (IR) therapy is still a common treatment option for patients with lymph nodes or brain metastasis. Thus, it is urgent to develop strategies to enhance the sensitivity of TNBC tumors to low‐dose IR. Here, the authors report that E3 ubiquitin ligase Ring finger protein 126 (RNF126) is important for IR‐induced ATR‐CHK1 pathway activation to enhance DNA damage repair (DDR). Mechanistically, RNF126 physically associates with the MRE11‐RAD50‐NBS1 (MRN) complex and ubiquitinates MRE11 at K339 and K480 to increase its DNA exonuclease activity, subsequent RPA binding, and ATR phosphorylation, promoting sustained DDR in a homologous recombination repair‐prone manner. Accordingly, depletion of RNF126 leads to increased genomic instability and radiation sensitivity in both TNBC cells and mice. Furthermore, it is found that RNF126 expression is induced by IR activating the HER2‐AKT‐NF‐κB pathway and targeting RNF126 expression with dihydroartemisinin significantly improves the sensitivity of TNBC tumors in the brain to IR treatment in vivo. Together, these results reveal that RNF126‐mediated MRE11 ubiquitination is a critical regulator of the DDR, which provides a promising target for improving the sensitivity of TNBC to radiotherapy. [ABSTRACT FROM AUTHOR]

Due to light being absorbed by water and scattered by suspended particles, color distortion, low image contrast, and detail loss are the common problems found in underwater images. We present an underwater image processing method, which based on an underwater imaging model, makes initial image restoration with the improved red channel prior combining transmission reduction, background light correction, and color compensation to acquire clearer underwater images, and then combines multiscale retinex (MSR) enhancement and hue saturation value to enhance image color contrast and saturation. Results indicate that, compared with the original images, the method proposed in this paper is capable of significantly enhancing image definition, saturation, contrast, and luminance. In comparison with dark channel prior, single-scale retinex (SSR), MSR, and multiscale retinex with color restoration (MSRCR), this method greatly improved the average gradient of images while keeping the information entropy of images unchanged. The average gradient calculated with the proposed method increased by 239%, 199%, 200%, and 220% for the three given images, respectively, compared with the other methods above. [ABSTRACT FROM AUTHOR]

Lysine-63-linked (K63-linked) polyubiquitination of TRAF3 coordinates the engagement of pattern-recognition receptors with recruited adaptor proteins and downstream activator TBK1 in pathways that induce type I IFN. Whether autoubiquitination or other E3 ligases mediate K63-linked TRAF3 polyubiquitination remains unclear. We demonstrated that mice deficient in the E3 ligase gene Hectd3 remarkably increased host defense against infection by intracellular bacteria Francisella novicida, Mycobacterium, and Listeria by limiting bacterial dissemination. In the absence of HECTD3, type I IFN response was impaired during bacterial infection both in vivo and in vitro. HECTD3 regulated type I IFN production by mediating K63-linked polyubiquitination of TRAF3 at residue K138. The catalytic domain of HECTD3 regulated TRAF3 K63 polyubiquitination, which enabled TRAF3-TBK1 complex formation. Our study offers insights into mechanisms of TRAF3 modulation and provides potential therapeutic targets against infections by intracellular bacteria and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint blockers (ICBs) are revolutionized therapeutic strategies for cancer, but most patients with solid neoplasms remain resistant to ICBs, partly because of the difficulty in reversing the highly immunosuppressive tumor microenvironment (TME). Exploring the strategies for tumor immunotherapy is highly dependent on the discovery of molecular mechanisms of tumor immune escape and potential therapeutic target. Krüppel-like Factor 5 (KLF5) is a cell-intrinsic oncogene to promote tumorigenesis. However, the cell-extrinsic effects of KLF5 on suppressing the immune response to cancer remain unclear. Methods: We analyzed the immunosuppressive role of KLF5 in mice models transplanted with KLF5-deleted/overexpressing tumor cells. We performed RNA sequencing, immunohistochemistry, western blotting, real time-PCR, ELISA, luciferase assay, chromatin immunoprecipitation (ChIP), and flow cytometry to demonstrate the effects of KLF5 on CD8 + T cell infiltration and related molecular mechanism. Single-cell RNA sequencing and spatial transcriptomics analysis were applied to further decipher the association between KLF5 expression and infiltrating immune cells. The efficacy of KLF5/COX2 inhibitors combined with anti-programmed cell death protein 1 (anti-PD1) therapy were explored in pre-clinical models. Finally, a gene-expression signature depending on KLF5/COX2 axis and associated immune markers was created to predict patient survival. Results: KLF5 inactivation decelerated basal-like breast tumor growth in a CD8 + T-cell-dependent manner. Transcriptomic profiling revealed that KLF5 loss in tumors increases the number and activated function of T lymphocytes. Mechanistically, KLF5 binds to the promoter of the COX2 gene and promotes COX2 transcription; subsequently, KLF5 deficiency decreases prostaglandin E2 (PGE2) release from tumor cells by reducing COX2 expression. Inhibition of the KLF5/COX2 axis increases the number and functionality of intratumoral antitumor T cells to synergize the antitumorigenic effects of anti-PD1 therapy. Analysis of patient datasets at single-cell and spatial resolution shows that low expression of KLF5 is associated with an immune-supportive TME. Finally, we generate a KLF5/COX2-associated immune score (KC-IS) to predict patient survival. Conclusions: Our results identified a novel mechanism responsible for KLF5-mediated immunosuppression in TME, and targeting the KLF5/COX2/PGE2 axis is a critical immunotherapy sensitizer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Out of the breast cancer subtypes, triple-negative breast cancer (TNBC) has the poorest prognosis without effective targeted therapies. Metformin, a first-line drug for type 2 diabetes mellitus, was demonstrated to target breast cancer stem cells selectively. However, the efficiency and the mechanism of action of metformin in TNBC are unclear. In this study, we demonstrated that metformin decreased the percentage of TNBC stem cells partially through the downregulation of the expression of the stem cell transcription factor Krüppel-like factor 5 (KLF5) and its downstream target genes, such as Nanog and FGF-BP1 , in TNBC cell lines. Metformin induced glycogen synthase kinase-3β (GSK3β)-mediated KLF5 protein phosphorylation and degradation through the inhibition of protein kinase A (PKA) activity in TNBC cells. Consistently, PKA activators increased the expression levels of KLF5. We observed a positive correlation between p-CREB, p-GSK3β, KLF5 and FGF-BP1 protein levels in human TNBC samples. These findings suggest that metformin suppresses TNBC stem cells partially through the PKA-GSK3β-KLF5 signaling pathway., Competing Interests: The authors declare no conflict of interest.

Objective: To observe the effect of cationic liposomal ceftazidime (CLC) combined with nano-hydroxyapatite/beta-tricalcium phosphate (n-HA/beta-TCP) in the treatment of chronic osteomyelitis of rabbits., Methods: Thirty healthy New Zealand white rabbits (4-6 months old; weighing, 2-3 kg) were selected to prepare the chronic osteomyelitis models. After 4 weeks, the gross observation, X-ray examination, and bacteriological and histopathological examinations were done; the models were made successfully in 27 rabbits. Of 27 rabbits, 24 were randomly divided into 4 groups (n = 6): only debridement was performed in group A; ceftazidime was given (90 mg/kg), twice a day for 8 weeks after debridement in group B; ceftazidime and n-HA/beta-TC were implanted after debridement in group C; and CLC and n-HA/beta-TCP were implanted after debridement in group D. Before and after treatments, X-ray examination was done, and Norden score was recorded. At 8 weeks after treatment, the specimens were harvested for gross observation and for gross bone pathological score (GBPS) using Rissing standard; half of the specimens was used for histological observation and Smeltzer scoring, the other half for bacteriological examination and calculation of the positive rate of bacteria culture., Results: At 8 weeks after treatment, Norden score of group D was significantly lower than that of groups A, B, and C (P < 0.05), but no significant difference was found among groups A, B, and C (P > 0.05). At 8 weeks after treatment, sinus healed in groups C and D, but sinus was observed in groups A and B; the GBPS scores of groups C and D were significantly lower than those of groups A and B (P < 0.05). The Smeltzer scores of groups C and D were significantly lower than those of groups A and B (P < 0.05). The positive rates of bacteria culture of groups C (0) and D (0) were significantly lower than those of group A (25.0%) and group B (16.7%) (P < 0.05)., Conclusion: CLC combined with n-HA/beta-TCP has good effect in treating chronic osteomyelitis of rabbits, and it has better effect in treating chronic osteomyelitis of rabbits than ceftazidime with n-HA/beta-TCP.

Objective: To prepare cationic Vancomycin hydrochloride multivesicular liposome (MVL) and to inspect its quality., Methods: Cationic Vancomycin hydrochloride MVLs were prepared by double emulsion method, and the storing solution of Vancomycin was prepared. The analysis method of Vancomycin in vitro was established; the specificity, precision, and resorption rate were estimated. Reverse phase high performance liquid chromatography (RP-HPLC) was used to determine the concentration of Vancomycin, encapsulation efficiency, and release characteristics in vitro. The formulation and pharmaceutical process were optimized by single factor experiments and orthogonal experimental design with the factor of encapsulation efficiency as the criteria. The liposome morphology was observed by optical microscopy and transmission electron microscopy. The particle size and Zeta potential were determined by Malvern instrument. The stability was analyzed by dynamic analysis., Results: An RP-HPLC method was established for the assay of Vancomycin. The analysis method was precise, simple, and reliable for the quality control of Vancomycin. Vancomycin hydrochloride MVLs were round and well-distributed. The average particle size and the encapsulation efficiency were 3.3 microm and 24.9%, respectively. Zeta potential was 24.53 mV, and 90.5% of Vancomycin hydrochloride was released after 264 hours in normal saline under 37 degrees C. Cationic Vancomycin MVLs were stored for 1 month at 4 degrees C, which mantained good stability., Conclusion: Cationic Vancomycin hydrochloride MVLs have good appearance, high encapsulation efficiency, good stability, and significant sustained release properties.

Objective: To reviewe the research progress of liposomes as antibiotic carriers., Methods: Domestic and abroad literature concerning liposomes as antibiotic carriers was reviewed and analyzed thoroughly., Results: Liposomes as antibiotic carriers can significantly improve drug distribution, enhance antibacterial activity, and reduce the side effects of antibiotics during treatment. But it also has some problems, such as poor physical and chemical stabilities and low encapsulation efficiency., Conclusion: Liposomes as antibiotic carriers can reduce the drug toxicity, improve drug biodistribution, and pharmacokinetics, and bring the dawn to completely curing infections disease.

Objective: To compare the effect of different defect diameters on healing in the middle 1/3 tibia monolayer cortical bone defect mouse model so as to establish an animal model for bone tissue engineering study, mechanism study on bone defect repair, and gene therapy research., Methods: Ten 8-week-old C57BL/6J mice, weighing (20 +/- 2) g, were randomly divided into 2 groups, 5 mice in each group. The middle 1/3 tibiae monolayer cortical bone defect model of 0.8 mm (group A) or 1.0 mm (group B) in diameter was established with burr drill. At 7, 21, and 28 days after modeling, the molybdenum target X-ray radiography was used to observe the defect repair; at 28 days, Micro CT and three-dimensional imaging were used to evaluate bone defect repair, and tibia specimens were harvested for HE staining., Results: At 7 days after modeling, tibia fracture occurred in 5 mice in group B, no fracture in group A. X-ray films, Micro CT scan, and HE staining showed bony union in group A at 28 days. The quantitative analysis of trabecular bone by Micro CT showed that trabecular number, connectivity density, and bone volume in group A were significantly greater than those in group B (P < 0.05), mean of segmented region--mean 2 was significantly less than that in group B (P < 0.05), but no significant difference was found in trabecular separation and trabecular thickness between 2 groups (P > 0.05)., Conclusion: The middle 1/3 tibia monolayer cortical bone defect mouse model of 0.8 mm in diameter is the ideal animal model for study repair mechanism of tibia defect or bone tissue engineering.