Glutathione is a valuable tri-peptide that is industrially produced by fermentation using the yeast Saccharomyces cerevisiae, and is widely used in the pharmaceutical, food, and cosmetic industries. It has been reported that addition of L-serine (L-Ser) is effective at increasing the intracellular glutathione content because L-Ser is the common precursor of L-cysteine (L-Cys) and glycine (Gly) which are substrates for glutathione biosynthesis. Therefore, we tried to enhance the L-Ser biosynthetic pathway in S. cerevisiae for improved glutathione production.

The volumetric glutathione production of recombinant strains individually overexpressing SER2, SER1, SER3, and SER33 involved in L-Ser biosynthesis at 48h cultivation was increased 1.3, 1.4, 1.9, and 1.9-fold, respectively, compared with that of the host GCI strain, which overexpresses genes involved in glutathione biosynthesis. We further examined simultaneous overexpression of SHM2 and/or CYS4 genes involved in Gly and L-Cys biosynthesis, respectively, using recombinant GCI strain overexpressing SER3 and SER33 as hosts. As a result, GCI overexpressing SER3, SHM2, and CYS4 showed the highest volumetric glutathione production (64.0 ± 4.9mg/L) at 48h cultivation, and this value is about 2.5-fold higher than that of the control strain.

This study first revealed that engineering of L-Ser and Gly biosynthetic pathway are useful strategies for fermentative glutathione production by S. cerevisiase.

This study first revealed that engineering of L-Ser and Gly biosynthetic pathway are useful strategies for fermentative glutathione production by S. cerevisiase.The failure of orthopedic and dental implants is mainly caused by biomaterial-associated infections and poor osseointegration. Surface modification of biomedical materials plays a significant role in enhancing osseointegration and anti-bacterial infection. In this work, a non-linear relationship between the micro/nano surface structures and the femtosecond laser processing parameters was successfully established based on an artificial neural network. Then a controllable functional surface with silver nanoparticles (AgNPs) to was produced to improve the cytocompatibility and antibacterial properties of biomedical titanium alloy. The surface topography, wettability, and Ag+ release were carefully investigated. The effects of these characteristics on antibacterial activity and cytocompatibilty were also evaluated. Results show that the prepared surface is hydrophobic, which can prevent the burst release of Ag+ in the initial stage. The prepared surface also shows both good cytocompatibility toward the murine calvarial preosteoblasts MC3T3-E1 cells (derived from Mus musculus (mouse) calvaria) and good antibacterial effects against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, which is caused by the combined effect of appropriate micro/nano-structured feature and reasonable Ag+ release rate. We do not only clarify the antibacterial mechanism but also demonstrate the possibility of balancing the antibacterial and osteointegration-promoting properties by micro/nano-structures. The reported method offers an effective strategy for the patterned surface modification of implants.

With the success of recent non-viral gene delivery-based COVID-19 vaccines, nanovectors have gained some public acceptance and come to the forefront of advanced therapies. Unfortunately, the relatively low ability of the vectors to overcome cellular barriers adversely affects their effectiveness. Scientists have thus been striving to develop ever more effective gene delivery vectors, but the results are still far from satisfactory. Therefore, developing novel strategies is probably the only way forward to bring about genuine change. Herein, we devise a brand-new gene delivery strategy to boost dramatically the transfection efficiency of two gold standard nucleic acid (NA)/polymer nanoparticles (polyplexes) in vitro.

We conceived a device to generate milli-to-nanoscale vibrational cues as a function of the frequency set, and deliver vertical uniaxial displacements to adherent cells in culture. A short-lived high-frequency vibrational load (t = 5min, f = 1,000Hz) caused abrupt and extensive plasmalemma outgiral vectors through priming adherent cells with a short vibrational stimulation. This study paves the way for capitalizing on physical cell stimulation(s) to significantly raise the effectiveness of gene delivery vectors in vitro and ex vivo.

Intestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments for UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD was elucidated in the dextran sulfate sodium (DSS)-induced colitis mouse model, a model to mimic UC.

Murine colitis was evaluated by comparing the disease activity index score. The intestinal inflammation was examined by histology analyses. The leukocyte infiltration in the colonic tissues was examined by immunohistochemistry analyses. The cytokines level in colonic tissues was examined by Multi-Plex immunoassay. The epithelial proliferation was evaluated by histological analyses. Immunofluorescence double staining was used to examine the expression of MMP-7 in the immune cells.

In the DSS-induced colitis mouse model, administration of PD attenuated the intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells. Immunohistochemical analyses further showed that matrix metalloproteinase-7 (MMP-7) expressed by the infiltrating leukocytes, including neutrophils and macrophages was inhibited by PD treatment. PD increases the cytokine level of IL-6 in colonic tissues.

PD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression.

PD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression.Breast cancer is the most common type of cancer in women and the second leading cause of cancer death in female. Triple-negative breast cancer has a more aggressive proliferation and a poorer clinical diagnosis than other breast cancers. The most common treatments for TNBC are chemotherapy, surgical removal, and radiation therapy, which impose many side effects and costs on patients. Nanobodies have superior advantages, which makes them attractive for use in therapeutic agents and diagnostic kits. There are numerous techniques suggested by investigators for early detection of breast cancer. Nevertheless, there are fewer molecular diagnostic methods in the case of TNBC due to the lack of expression of famous breast cancer antigens in TNBC. Although conventional antibodies have a high ability to detect tumor cell markers, their large size, instability, and costly production cause a lot of problems. Since the HER-2 do not express in TNBC diagnosis, the production of nanobodies for the diagnosis and treatment of cancer cells should be performed against other antigens expressed in TNBC. In this review, nanobodies which developed against triple negative breast cancer, were classified based on type of antigen.

High bone mass (HBM, BMD Z-score ≥  + 3.2) and cam morphology (bulging of lateral femoral head) are associated with greater odds of prevalent radiographic hip osteoarthritis (rHOA). As cam morphology is itself a manifestation of increased bone deposition around the femoral head, it is conceivable that cam morphology may mediate the relationship between HBM and rHOA. We therefore aimed to determine if individuals with HBM have increased odds of prevalent cam morphology. In addition, we investigated whether the relationship between cam and prevalent and incident osteoarthritis was preserved in a HBM population.

In the HBM study, a UK based cohort of adults with unexplained HBM and their relatives and spouses (controls), we determined the presence of cam morphology using semi-automatic methods of alpha angle derivation from pelvic radiographs. Associations between HBM status and presence of cam morphology, and between cam morphology and presence of rHOA (or its subphenotypes osteophytes, joint space narrowinhritis (OR = 0.76 [0.16-3.49], p = 0.72).

The relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

The relationship between cam morphology and rHOA seen in other studies is preserved in a HBM population. This study suggests that the risk of OA conferred by high BMD and by cam morphology are mediated via distinct pathways.

Using cohort data from the Japan Environment and Children’s Study (JECS), we previously reported that the risk of sleep deprivation in 1-year-old children was reduced with a higher maternalintake of fermented foods, particularly miso. The present study, which evaluates children from the same cohort at 3 years of age, is a continuation of that work.

After applying exclusion criteria to 104,062 records in the JECS dataset, we evaluated 64,200 mother-child pairs in which the child was 3 years old. We examined the association of the dietary intake of fermented foods during pregnancy with child sleep duration < 10 h at the age of 3 years.

Multivariable logistic regression analysis with the lowest quartile used as a reference revealed adjusted odds ratios (95% confidence intervals) for the second through fourth quartiles of 0.98 (0.90-1.06), 0.93 (0.85-1.01), and 0.85 (0.78-0.94) for cheese intake.

The consumption of fermented foods during pregnancy is associated with reduced risk of sleep deprivation in 3-year-old children, albeit in a limited way.

The consumption of fermented foods during pregnancy is associated with reduced risk of sleep deprivation in 3-year-old children, albeit in a limited way.

TIR domain containing adaptor molecule 1 (TICAM1) is a coding gene participating in immune and inflammation responses to malignant cells. However, the role of TICAM1 in Wilms tumor (WT) is rarely known.

The expression level of TICAM1 was calculated in the WT TARGET cohort and validated using the GSE66405 cohort. The Kaplan-Meier method was employed to investigate the potential clinical value of TICAM1 and the association between its expression level and clinical features. The influence of TICAM1 on immune infiltration was examined by ESTIMATE, CIBERSORT and MCPcounter algorithms. IC50 of chemotherapeutic drugs was calculated by „pRRophetic” R package.

TICAM1 was downregulated in WT patients with worse prognosis and a more advanced clinical stage. Moreover, a low expression level of TICAM1 contributed to less immune cell infiltration, few protective immune cells and more antitumor immune cells.

TICAM1 exerts a significant impact on the prognosis, progression and immune infiltration condition of WT.

TICAM1 exerts a significant impact on the prognosis, progression and immune infiltration condition of WT.