Vancomycin-Loaded Sol-Gel System for In Situ Coating of Artificial Bone to Prevent Surgical Site Infections.

Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.

A self-assembling peptide inhibits the growth and function of fungi via a wrapping strategy.

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.

Research on coal mine safety management based on digital twin.

Coal mine safety management is the foundation and decisive factor of coal mining. The manual detection model is the main way for traditional coal mine safety management, which has problems such as inefficient identification of safety risks in coal mines, poor control accuracy and slow response measures and so on. Therefore, to make up for the shortcomings in the traditional coal mine safety management model, this paper introduces digital twin technology into coal mine safety management to achieve intelligent and efficient management of coal mine safety accidents. Firstly, we introduce the digital twin technology, select the five-dimensional model as the modeling basis, based on the existing twin model architecture, analyze the types of coal mine accidents and disasters, select the most destructive gas accidents as the research object, construct a twin safety management model for coal mine gas accidents using the digital twin five-dimensional model. Secondly, analyses of the actual operation mechanism of the digital twin model, and the advantages of the twin model in achieving prior prevention, rapid response and accurate control of gas incidents are pointed out. Finally, the house of quality of the gas accident digital twin model is established through the quality functional deployment tool, and key technical requirements for the construction of the twin model are given to accelerate the application of the gas accident twin model in the field. This study innovatively introduces digital twin technology into the field of coal mine safety management, proposes the application scenarios of emerging technologies such as digital twins in the coal mine field, and provides the possibility of multi-scene application of smart mine construction and technologies such as digital twins.

Case Report: Cranial Tuberculosis in a Patient without Tuberculosis Foci Elsewhere in the Body.

Cranial tuberculosis is a relatively infrequent inflammatory reaction caused by tuberculous bacilli invading the skull. Most cases of cranial tuberculosis are secondary to tuberculosis foci in other parts of the body; primary cranial tuberculosis is extremely rare. Herein, we report a case of primary cranial tuberculosis. A 50-year-old man presented to our hospital with a mass in the right frontotemporal region. Chest computed tomography and abdominal ultrasonography findings were normal. Magnetic resonance imaging of the brain revealed a mass in the right frontotemporal skull and scalp with cystic changes, adjacent bone destruction, and meningeal invasion. The patient underwent surgery and was diagnosed with primary cranial tuberculosis; he was treated with antitubercular therapy postoperatively. No recurrent masses or abscesses were observed during the follow-up.

Corrigendum: Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB.

[This corrects the article DOI: 10.3389/fimmu.2023.1102578.].

Bioinformatics analysis and consistency verification of a novel tuberculosis vaccine candidate HP13138PB.

Background: With the increasing incidence of tuberculosis (TB) and the shortcomings of existing TB vaccines to prevent TB in adults, new TB vaccines need to be developed to address the complex TB epidemic. Method: The dominant epitopes were screened from antigens to construct a novel epitope vaccine termed HP13138PB. The immune properties, structure, and function of HP13138PB were predicted and analyzed with bioinformatics and immunoinformatics. Then, the immune responses induced by the HP13138PB were confirmed by enzyme-linked immunospot assay (ELISPOT) and Th1/Th2/Th17 multi-cytokine detection kit. Result: The HP13138PB vaccine consisted of 13 helper T lymphocytes (HTL) epitopes, 13 cytotoxic T lymphocytes (CTL) epitopes, and 8 B-cell epitopes. It was found that the antigenicity, immunogenicity, and solubility index of the HP13138PB vaccine were 0.87, 2.79, and 0.55, respectively. The secondary structure prediction indicated that the HP13138PB vaccine had 31% of α-helix, 11% of ß-strand, and 56% of coil. The tertiary structure analysis suggested that the Z-score and the Favored region of the HP13138PB vaccine were -4.47 88.22%, respectively. Furthermore, the binding energies of the HP13138PB to toll-like receptor 2 (TLR2) was -1224.7 kcal/mol. The immunoinformatics and real-world experiments showed that the HP13138PB vaccine could induce an innate and adaptive immune response characterized by significantly higher levels of cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and IL-10. Conclusion: The HP13138PB is a potential vaccine candidate to prevent TB, and this study preliminarily evaluated the ability of the HP13138PB to generate an immune response, providing a precursor target for developing TB vaccines.

An intelligent peptide recognizes and traps Mycobacterium tuberculosis to inhibit macrophage phagocytosis.

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.

Elevated RECQL1 expression predicts poor prognosis and associates with tumor immune infiltration in low-grade glioma.

Background: Dysregulation of RecQ protein-like 1 (RECQL1), a member of the RecQ DNA helicase, has been determined to participate in malignant process of numerous tumors such as immunosuppression and proliferation and may serve as a biomarker for certain malignancies. Nevertheless, whether there is a similar association between RECQL1 and low-grade glioma (LGG) is uncertain. We therefore turned our attention to exploring the association of RECQL1 with tumor immune infiltration and prognostic significance in LGG. Methods: The differential expression analysis of the RecQ DNA helicases was conducted through the GLIOVIS database and GSE4290 dataset, and verified by the Gene Expression Profiling Interactive Analysis 2 database. Kaplan-Meier plots, Univariate and multivariate Cox regression analysis were employed to assess the prognostic value of RECQL1 expression level and other six variables in LGG patients, and subsequently an efficient nomogram model was generated for clinical prediction. Tumor Immune Estimation Resource database and the single sample Gene Set Enrichment Analysis were used to assess the correlation between RECQL1 and immune infiltration of LGG. The biological processes that may be related to RECQL1 in LGG were learned through functional enrichment analysis by Gene Set Enrichment Analysis software. Results: Among the five RecQ DNA helicases detected, only RECQL1 was over-expression in LGG with the most convincing evidence (log2FoldChange >1.5, q value <0.01). High RECQL1 expression demonstrated worse overall survival and progression-free survival of LGG patients (P<0.05). Dysregulation of RECQL1 was an independent prognostic indicator for outcomes of LGG (HR >1.4, P<0.05). RECQL1 may participates in the carcinogenic pathways of LGG such as adherens junction and JAK-STAT signaling pathways. The transcription expression level of RECQL1, was obviously associated with tumor immune infiltrating cells and their marker genes. Conclusions: High RECQL1 expression detected in LGG not only implies adverse clinical outcome of patients, but also correlates with tumor immune infiltration and certain oncogenic pathways. Our study proposes potential novel biomarker and therapeutic target for the treatment of LGG patients.

Heterologous expression and activity verification of ornithine decarboxylase from a wild strain of Shewanella xiamenensis.

Shewanella xiamenensis is widely found in spoilage fish, shrimp and other seafoods. Under suitable conditions, ornithine can be synthesized into putrescine, which may spoil food or endanger health. Our research used a wild strain of Shewanella xiamenensis isolated from "Yi Lu Xian" salted fish (a salting method for sea bass) as a research object. According to the database of National Center of Biotechnology Information (NCBI), the target ornithine decarboxylase (ODC) gene SpeF was successfully amplified using the wild strain of Shewanella xiamenensis as the template. Sequencing alignment showed that the SpeF of the wild strain had more than 98% homology compared with the standard strain. The amino acid substitution occurred in the residues of 343, 618, 705, and 708 in the wild strain. After optimizing the expression conditions, a heterologous expression system of ODC was constructed to achieve a high yield of expression. The amount of 253.38 mg of ODC per liter of LB broth was finally expressed. High performance liquid chromatography (HPLC) and subsequent ODC activity verification experiments showed that hetero-expressed ODC showed a certain enzyme activity for about 11.91 ± 0.38 U/mg. Our study gives a new way to the development of a low-cost and high-yield strategy to produce ODC, providing experimental materials for further research and elimination of putrescine in food hazards.

Functional Characterization of the EMBRYONIC FLOWER 2 Gene Involved in Flowering in Ginkgo biloba.

Ginkgo biloba has edible, medicinal, and ornamental value. However, the long juvenile phase prevents the development of the G. biloba industry, and there are few reports on the identification and functional analysis of genes regulating the flowering time of G. biloba. EMBRYONIC FLOWER 2 (EMF), an important protein in flower development, functions to promote vegetative growth and repress flowering. In this study, a novel EMF gene (GbEMF2) was cloned and characterized from G. biloba. GbEMF2 contains a 2,193 bp open reading frame (ORF) encoding 730 amino acids. GbEMF2 harbors conserved VEFS-Box domain by the plant EMF protein. The phylogenic analysis showed that GbEMF2 originated from a polycomb-group (Pc-G) protein ancestor and was a member of the EMF2 protein. The quantitative real-time PCR (qRT-PCR) analysis revealed that GbEMF2 was expressed in all detected organs, and it showed a significantly higher level in ovulating strobilus and microstrobilus than in other organs. Compared with emf2 mutant plants, overexpression of GbEMF2 driven by the CaMV 35S promoter in emf2 mutant Arabidopsis plants delayed flowering but earlier than wild-type (WT) plants. This result indicated that GbEMF2 repressed flowering in G. biloba. Moreover, the RNA-seq analysis of GbEMF2 transgenic Arabidopsis plants (GbEMF2-OE/emf2), WT plants, and emf2 mutants screened out 227 differentially expressed genes (DEGs). Among these DEGs, FLC, MAF5, and MAF5-1 genes were related to flower organ development and regulated by GbEMF2. In addition, some genes participating in sugar metabolism, such as Alpha-amylase 1 (AMY1), BAM1, and Sucrose synthase 3 (SUS3) genes, were also controlled by GbEMF2. Overall, our results suggested that GbEMF2 negatively regulates flowering development in G. biloba. This finding provided a foundation and target gene for shortening the Ginkgo juvenile period by genetic engineering technology.

Modified Atmosphere Packaging Maintains the Sensory and Nutritional Qualities of Post-harvest Baby Mustard During Low-Temperature Storage.

Baby mustard is a popular, yet highly perishable, Brassica vegetable. There is a need to develop effective methods for maintaining post-harvest qualities of baby mustard. Here, the lateral buds of baby mustard were packed in transparent polyethylene bags with no holes (M0), 6 mm in diameter holes (M1), or 12 mm in diameter holes (M2) and stored at 4°C. The effect of different modified atmosphere packaging (MAP) treatments on the sensory quality, health-promoting compounds, and antioxidant capacity was investigated by comparison with non-wrapped baby mustard. M1 and M2 delayed sensory quality deterioration and slowed declines in the content of ascorbic acid, total phenolics, and glucosinolates and antioxidant capacity during storage. M1 was most effective in prolonging the shelf life (three additional days compared with control lateral buds) and maintaining the content of glucosinolates. However, M0 accelerated the decline in the odor score, acceptability score, and ascorbic acid content and shortened the shelf life of baby mustard by more than 5 d compared with the control. These findings indicate that the effect of MAP treatment depends on the size of the holes in the bag. Based on these results, M1 was an alternative method for prolonging the shelf life and maintaining post-harvest qualities of baby mustard stored at 4°C.

Microfluidic self-assembly of high cabazitaxel loading albumin nanoparticles.

Cabazitaxel (CTX) is a promising anticancer drug. In this study, CTX-loaded human serum albumin (HSA) nanoparticles (MF-NPs-CTX) were prepared by a microfluidic (MF) method and were evaluated for tumor inhibition in PC-3 and HeLa cells in vitro and in vivo. The in vitro experiments showed that MF-NPs-CTX had higher drug loading content (DLC) as compared with NPs prepared by the bottom-up (BU) method (BU-NPs-CTX). Besides, MF-NPs-CTX exhibited uniform particle size distribution, high stability, sustained drug release, and high biosafety, in vivo imaging studies demonstrated that MF-NPs-CTX accumulated preferentially at the tumor site, compared to BU-NPs-CTX. The enhanced tumor uptake also increased the therapeutic efficacy of MF-NPs-CTX. Both MF-NPs-CTX and tween-CTX exhibited good tumor inhibition effect in vivo. MF-NPs-CTX had better biosafety and biocompatibility than tween-CTX. These results demonstrated that high CTX loading of MF-NPs-CTX has potential in the clinical treatment of tumors.

Dynamic Analysis of the Time-Delayed Genetic Regulatory Network Between Two Auto-Regulated and Mutually Inhibitory Genes.

Time delays play important roles in genetic regulatory networks. In this paper, a gene regulatory network model with time delays and mutual inhibition is considered, where time delays are regarded as bifurcation parameters. In the first part of this paper, we analyze the associated characteristic equations and obtain the conditions for the stability of the system and the existence of Hopf bifurcations in five special cases. Explicit formulas are given to determine the direction and stability of the Hopf bifurcation by using the normal form method and the center manifold theorem. Numerical simulations are then performed to illustrate the results we obtained. In the second part of the paper, using time-delayed stochastic numerical simulations, we study the impact of biological fluctuations on the system and observe that, in modest noise regimes, unexpectedly, noise acts to stabilize the otherwise destabilized oscillatory system.

Folate Receptor-Targeted Albumin Nanoparticles Based on Microfluidic Technology to Deliver Cabazitaxel.

Microfluidic technology (MF) has improved the formulation of nanoparticles (NPs) by achieving uniform particle size distribution, controllable particle size, and consistency. Moreover, because liquid mixing can be precisely controlled in the pores of the microfluidic chip, maintaining high mixing efficiency, MF exerts higher of NP encapsulation efficiency (EE) than conventional methods. MF-NPs-cabazitaxel (CTX) particles (MF-NPs-CTX) were first prepared by encapsulating CTX according to MF. Folate (FA)- Polyethylene glycol (PEG)-NPs-CTX particles (FA-PEG-NPs-CTX) were formulated by connecting FA to MF-NPs-CTX to endow NPs with targeted delivery capability. Accordingly, the mean particle size of FA-PEG-NPs-CTX increased by approximately 25 nm, as compared with MF-NPs-CTX. Upon morphological observation of FA-PEG-NPs-CTX and MF-NPs-CTX by transmission electron microscopy (TEM), all NPs were spherical and particle size distribution was uniform. Moreover, the increased delivery efficiency of CTX in vitro and its strong tumor inhibition in vivo indicated that FA-PEG-NPs-CTX had a powerful tumor-suppressive effect both in vitro and in vivo. In vivo imaging and pharmacokinetic data confirmed that FA-PEG-NPs-CTX had good drug delivery efficiency. Taken together, FA-PEG-NPs-CTX particles prepared using MF showed high efficient and targeted drug delivery and may have a considerable driving effect on the clinical application of targeting albumin NPs.

Stability and Hopf bifurcation analysis in a delayed three-node circuit involving interlinked positive and negative feedback loops.

A system involving interlinked positive and negative feedback loops is a flexible motif that can tune itself in gene regulatory networks. It is well known that time delay is inevitable in gene regulatory networks due to transcription and translation not being physically co-located. In this paper, we systematically consider the effect of time delay on the dynamical behavior of the three-node circuit with three time delays. Based on linear stability analysis and bifurcation theory, sufficient conditions for stability of equilibria and oscillatory behaviors via Hopf bifurcation are derived when choosing positive and negative feedback strengths as well as time delays τ1, τ2, τ3 as the bifurcation parameters, respectively. Moreover, stability and direction of the Hopf bifurcation of time delay are studied by using the normal form method and the center manifold theorem. Finally, several examples are performed to illustrate some analytical results we obtained.

Temperature dependence of photoemission characteristics from AlxGa1-xAs/GaAs photocathodes.

In this work, photon-enhanced thermionic emission (PETE), which simultaneously harvests solar photonic and thermionic energies, is studied theoretically and experimentally with a transmission-mode AlxGa1-xAs/GaAs cathode within a compact photodiode. The effect of temperature on energy distribution and photoemission yield was experimentally studied in the wavelength range 450-850 nm. The variation of the energy distribution with increasing temperatures demonstrates that direct photoemission gradually declines, while PETE contribution increases with increased heat. Further quantitative proof of the PETE phenomenon can be observed at 850 nm, as temperature increases from 20°C to 90°C. The PETE model with the t-mode AlxGa1-xAs/GaAs cathode is deduced, and the temperature dependence of electron affinity can be achieved. The results show promising applications of the AlxGa1-xAs/GaAs cathode in combined solar/thermal energy conversion.

Isolation and functional characterization of a circadian-regulated CONSTANS homolog (GbCO) from Ginkgo biloba.

KEY MESSAGE: This is the first report to clone and functionally characterize a flowering time gene GbCO in perennial gymnosperm Ginkgo biloba. GbCO complements the co mutant of Arabidopsis, restoring normal early flowering. CONSTANS (CO) is a central regulator of photoperiod pathway, which channels inputs from light, day length, and circadian clock to promote the floral transition. In order to understand the role of CO in gymnosperm Ginkgo biloba, which has a long juvenile phase (15-20 years), a CO homolog (GbCO) was isolated and characterized from G. biloba. GbCO encodes a 1741-bp gene with a predicted protein of 400 amino acids with two zinc finger domains (B-box I and B-box II) and a CCT domain. Phylogenic analysis classified GbCO into the group 1a clade of CO families in accordance with the grouping scheme for Arabidopsis CO (AtCO). Southern blot analysis indicated that GbCO belongs to a multigene family in G. biloba. Real-time PCR analysis showed that GbCO was expressed in aerial parts of Ginkgo, with the highest transcript level of GbCO being observed in shoot apexes. GbCO transcript level exhibited a strong diurnal rhythm under flowering-inductive long days and peaked during early morning, suggesting that GbCO is tightly coupled to the floral inductive long-day signal. In addition, an increasing trend of GbCO transcript level was observed both in shoot tips and leaves as the shoot growth under long-day condition, whereas GbCO transcript level decreased in both tissues under short-day condition prior to growth cessation of shoot in G. biloba. GbCO complemented the Arabidopsis co-2 mutant, restoring normal early flowering. All the evidence being taken together, our findings suggested that GbCO served as a potential inducer of flowering in G. biloba.

[Application and Thinking of Constitution Theory of Chinese Medicine in Stable Phase Chronic Ob- structive Pulmonary Disease].

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, but seriously threatens to patients' body and mind. Constitutions of Chinese medicine (CM) are closely relat- ed to diseases. Individuals with different constitutions of CM have different responses to the same envi- ronment and the same pathogenic factor. Therefore, studying the application of constitution theory of CM in stable phase COPD is of great significance. In this paper clinical applications of constitution theory of CM in COPD were explored from etiology and mechanism, syndrome typing based treatment, prevention and care, aiming to prevent, diagnose, and treat COPD effectively.

[Effect of Brucea javanica fruit oil emulsion combined cisplatin on the growth inhibition of transplanted tumor in human ovarian cancer SKOV3 nude mice: an experimental study].

OBJECTIVE: To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice. METHODS: Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot. RESULTS: The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05). CONCLUSIONS: Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.

A robust transparent and anti-fingerprint superhydrophobic film.

A thin film of polyaniline (PANI) nanofibers on the stainless steels with fluoro-thiol modification was prepared through an optimal polymerization time of aniline using HClO4 as a dopant, showing robust superhydrophobic, transparent and anti-fingerprint properties.