Combined biochar and wheat-derived endophytic bacteria reduces cadmium uptake in wheat grains in a metal-polluted soil.

In this study, two wheat-derived cadmium (Cd)-immobilizing endophytic Pseudomonas paralactis M14 and Priestia megaterium R27 were evaluated for their effects on wheat tissue Cd uptake under hydroponic conditions. Then, the impacts of the biochar (BC), M14+R27 (MR), and BC+MR treatments on wheat Cd uptake and the mechanisms involved were investigated at the jointing, heading, and mature stages of wheat plants under field-plot conditions. A hydroponic experiment showed that the MR treatment significantly decreased the above-ground tissue Cd content compared with the M14 or R27 treatment. The BC+MR treatment reduced the grain Cd content by 51.5%-67.7% and Cd translocation factor at the mature stage of wheat plants and increased the organic matter-bound Cd content by 31%-75% in the rhizosphere soils compared with the BC or MR treatment. Compared with the BC or MR treatment, the relative abundances of the biomarkers associated with Gemmatimonas, Altererythrobacter, Gammaproteobacteria, Xanthomonadaceae, Phenylobacterium, and Nocardioides in the BC+MR-treated rhizosphere microbiome decreased and negatively correlated with the organic matter-bound Cd contents. In the BC+MR-treated root interior microbiome, the relative abundance of the biomarker belonging to Exiguobacterium increased and negatively correlated with the Cd translocation factor, while the relative abundance of the biomarker belonging to Pseudonocardiaceae decreased and positively correlated with the Cd translocation factor. Our findings suggested that the BC+MR treatment reduced Cd availability and Cd transfer through affecting the abundances of these specific biomarkers in the rhizosphere soil and root interior microbiomes, leading to decreased wheat grain Cd uptake in the contaminated soil.

Effects of salinity and betaine addition on anaerobic granular sludge properties and microbial community succession patterns in organic saline wastewater.

In this study, the effects of different salinity gradients and addition of compatible solutes on anaerobic treated effluent water qualities, sludge characteristics and microbial communities were investigated. The increase in salinity resulted in a decrease in particle size of the granular sludge, which was concentrated in the range of 0.5-1.0 mm. The content of EPS (extracellular polymeric substances) in the granular sludge gradually increased with increasing salinity and the addition of betaine (a typical compatible solute). Meanwhile, the microbial community structure was significantly affected by salinity, with high salinity reducing the diversity of bacteria. At higher salinity, Patescibacteria and Proteobacteria gradually became the dominant phylum, with relative abundance increasing to 13.53% and 12.16% at 20 g/L salinity. Desulfobacterota and its subordinate Desulfovibrio, which secrete EPS in large quantities, dominated significantly after betaine addition.Their relative abundance reached 13.65% and 7.86% at phylum level and genus level. The effect of these changes on the treated effluent was shown as the average chemical oxygen demand (COD) removal rate decreased from 82.10% to 79.71%, 78.01%, 68.51% and 64.55% when the salinity gradually increased from 2 g/L to 6, 10, 16 and 20 g/L. At the salinity of 20 g/L, average COD removal increased to 71.65% by the addition of 2 mmol/L betaine. The gradient elevated salinity and the exogenous addition of betaine played an important role in achieving stability of the anaerobic system in a highly saline environment, which provided a feasible strategy for anaerobic treatment of organic saline wastewater.

The impact of endocrine-disrupting chemicals on stem cells: Mechanisms and implications for human health.

Endocrine-disrupting chemicals (EDCs) are compounds, either natural or man-made, that interfere with the normal functioning of the endocrine system. There is increasing evidence that exposure to EDCs can have profound adverse effects on reproduction, metabolic disorders, neurological alterations, and increased risk of hormone-dependent cancer. Stem cells (SCs) are integral to these pathological processes, and it is therefore crucial to understand how EDCs may influence SC functionality. This review examines the literature on different types of EDCs and their effects on various types of SCs, including embryonic, adult, and cancer SCs. Possible molecular mechanisms through which EDCs may influence the phenotype of SCs are also evaluated. Finally, the possible implications of these effects on human health are discussed. The available literature demonstrates that EDCs can influence the biology of SCs in a variety of ways, including by altering hormonal pathways, DNA damage, epigenetic changes, reactive oxygen species production and alterations in the gene expression patterns. These disruptions may lead to a variety of cell fates and diseases later in adulthood including increased risk of endocrine disorders, obesity, infertility, reproductive abnormalities, and cancer. Therefore, the review emphasizes the importance of raising broader awareness regarding the intricate impact of EDCs on human health.

4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway.

4-Nitrophenol (4-NP), as a toxic and refractory pollutant, has generated significant concern due to its adverse effects. However, the potential toxic effects and mechanism remained unclear. In this study, the reproduction, development, locomotion and reactive oxygen species (ROS) production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity. We used metabolomics to assess the potential damage mechanisms. The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis. 4-NP (8 ng/L and 8 µg/L) caused significant reduction of brood size, ovulation rate, total germ cells numbers, head thrashes and body bends, and an increase in ROS. However, the oosperm numbers in uterus, body length and body width were decreased in 8 µg/L. Moreover, 36 differential metabolites were enriched in the significant metabolic pathways, including lysine biosynthesis, ß-alanine metabolism, tryptophan metabolism, pentose phosphate pathway, pentose and glucuronate interconversions, amino sugar and nucleotide sugar metabolism, starch and sucrose metabolism, galactose metabolism, propanoate metabolism, glycerolipid metabolism, and estrogen signaling pathway. The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid, which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism, and finally affected the estrogen signaling pathway to exert toxic effects. Moreover, correlation and mediation analysis showed glycerol-3P, glucosamine-6P, glucosamine-1P, UDP-galactose, L-aspartic acid, and uracil were potential markers for the reproduction and glucose-1,6P2 for developmental toxicity. The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

Different fates of Sb(III) and Sb(V) during the formation of jarosite mediated by Acidithiobacillus ferrooxidans.

Secondary iron-sulfate minerals such as jarosite, which are easily formed in acid mine drainage, play an important role in controlling metal mobility. In this work, the typical iron-oxidizing bacterium Acidithiobacillus ferrooxidans ATCC 23270 was selected to synthesize jarosite in the presence of antimony ions, during which the solution behavior, synthetic product composition, and bacterial metabolism were studied. The results show that in the presence of Sb(V), Fe2+ was rapidly oxidized to Fe3+ by A. ferrooxidans and Sb(V) had no obvious effect on the biooxidation of Fe2+ under the current experimental conditions. The presence of Sb(III) inhibited bacterial growth and Fe2+ oxidation. For the group with Sb(III), products with amorphous phases were formed 72 hr later, which were mainly ferrous sulfate and pentavalent antimony oxide, and the amorphous precursor was finally transformed into a more stable crystal phase. For the group with Sb(V), the morphology and structure of jarosite were changed in comparison with those without Sb. The biomineralization process was accompanied by the removal of 94% Sb(V) to form jarosite containing the Fe-Sb-O complex. Comparative transcriptome analysis shows differential effects of Sb(III) and Sb(V) on bacterial metabolism. The expression levels of functional genes related to cell components were much more downregulated for the group with Sb(III) but much more regulated for that with Sb(V). Notably, cytochrome c and nitrogen fixation-relevant genes for the A.f_Fe2+_Sb(III) group were enhanced significantly, indicating their role in Sb(III) resistance. This study is of great value for the development of antimony pollution control and remediation technology.

Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Effect of Egyptian spitting cobra Naja nubiae crude venom on immunogenic activity of rats.

Snakes show defensive activities, often counting visual or auditory displays against an aggressor. The study observed what happens to rats administered subcutaneously sub-lethal doses of crude venom Naja nubiae. The pro-inflammatory cytokines, such as tumor necrosis alpha (TNF-α) and interleukin-6 (IL-6), as well as the anti-inflammatory cytokines such as interleukin-10 (IL-10), and inflammatory mediator's prostaglandin E-2 (PG-E2), were evaluated. Vascular permeability (VP) was employed to assess how leaky or permeable blood vessels are in various tissues and organs, including the rat peritoneal cavity and lymphoid organs. Lymphoid organs' histological alterations brought on by Nubiae venom. The study found that the two venom doses-1/4 and 1/2 LD50-induced high levels of inflammatory activity as evidenced by the production of inflammatory cytokines. These findings demonstrated that venom enhanced innate immunity through specifically increased T helper cells, IL-6, TNF-α, IL-10, and PG-E2. The results reveal whether the venom has an immunomodulatory effect and promotes inflammation. The data have a substantial impact on the development of new drugs and treatments for inflammatory conditions.

Controlled release of manganese and magnesium ions by microsphere-encapsulated hydrogel enhances cancer immunotherapy.

Despite the considerable potential of immune checkpoint blockade (ICB) therapy in treating various cancer types, it faces several challenges, of which the constrained objective response rate and relatively short duration of response observed in patients with cancer are the most important. This study introduces an injectable temperature-sensitive hydrogel, Pluronic F-127 (PF-127)@MnCl2/ alginate microspheres (ALG-MS)@MgCl2, that enhances the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) in cancer cells. The hydrogel material used in this study facilitated the rapid release of a significant amount of manganese ions (Mn2+) and the gradual and sustained release of magnesium ions (Mg2+) within the tumor microenvironment. This staged release profile promotes an immune microenvironment conducive to the cytotoxicity of CD8+ T cells and natural killer cells, thereby enhancing the efficacy of ICB therapy. Furthermore, the PF-127@MnCl2/ALG-MS@MgCl2 composite hydrogel exhibits the ability to convert drug-resistant tumor ("cold tumor") with a low PD-L1 response to a "hot tumor" with a high PD-L1 response. In summary, the PF-127@MnCl2/ALG-MS@MgCl2 hydrogel manipulates the immune microenvironment through the precise discharge of Mg2+ and Mn2+, thus, augmenting the efficacy of ICB therapy.

Recombinant collagen coating 3D printed PEGDA hydrogel tube loading with differentiable BMSCs to repair bile duct injury.

Bile duct injury presents a significant clinical challenge following hepatobiliary surgery, necessitating advancements in the repair of damaged bile ducts is a persistent issue in biliary surgery. 3D printed tubular scaffolds have emerged as a promising approach for the repair of ductal tissues, yet the development of scaffolds that balance exceptional mechanical properties with biocompatibility remains an ongoing challenge. This study introduces a novel, bio-fabricated bilayer bile duct scaffold using a 3D printing technique. The scaffold comprises an inner layer of polyethylene glycol diacrylate (PEGDA) to provide high mechanical strength, and an outer layer of biocompatible, methacryloylated recombinant collagen type III (rColMA) loaded with basic fibroblast growth factor (bFGF)-encapsulated liposomes (bFGF@Lip). This design enables the controlled release of bFGF, creating an optimal environment for the growth and differentiation of bone marrow mesenchymal stem cells (BMSCs) into cholangiocyte-like cells. These cells are instrumental in the regeneration of bile duct tissues, evidenced by the pronounced expression of cholangiocyte differentiation markers CK19 and CFTR. The PEGDA//rColMA/bFGF@Lip bilayer bile duct scaffold can well simulate the bile duct structure, and the outer rColMA/bFGF@Lip hydrogel can well promote the growth and differentiation of BMSCs into bile duct epithelial cells. In vivo experiments showed that the scaffold did not cause cholestasis in the body. This new in vitro pre-differentiated active 3D printed scaffold provides new ideas for the study of bile duct tissue replacement.

2'-ß-Methylselenyl nucleos(t)ide analogs as reverse transcriptase inhibitors against diverse HIV mutants.

Nucleoside reverse transcriptase inhibitors (NRTIs) have been extensively studied as drugs targeting HIV RT. However, the practice or use of approved NRTIs lacking the 3'-hydroxy group often promotes frequent HIV mutations and generates drug-resistance. Here, we describe a novel NRTI with 2'-ß-methylselenyl modification. We found that this modification inhibited the DNA elongation reaction by HIV-1 RT despite having a 3'-hydroxy group. Moreover, the conformation of this nucleoside analog is controlled at C3'-endo, a conformation that resists excision from the elongating DNA by HIV RT. Accordingly, the designed analogs exhibited activity against both wild-type HIV and multidrug-resistant HIV mutants.

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death.

Hepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs.

O/W nanoemulsions encapsulated octacosanol: Preparation, characterization and anti-fatigue activity.

Octacosanol has various biological effects such as antioxidant, hypolipidemic and anti-fatigue. However, poor solubility has limited the application of octacosanol in food. The aim of this study was to prepare octacosanol nanoemulsions with better solubility, stability and safety and to investigate in vivo anti-fatigue effect. The food-grade formulation of the octacosanol nanoemulsions consisted of octacosanol, olive oil, Tween 80, glycerol and water with 0.1 %, 1.67 %, 23.75 %, 7.92 % and 66.65 % (w/w), respectively. The nanoemulsions had an average particle size of 12.26 ± 0.76 nm and polydispersity index of 0.164 ± 0.12, and showed good stability under different pH, cold, heat, ionic stress and long-term storage conditions. The results of animal experiments showed that the octacosanol nanoemulsions significantly prolonged the fatigue tolerance time, alleviated the fatigue-related biochemical indicators, and weakened the oxidative stress. Meanwhile, octacosanol nanoemulsions upregulated hepatic glycogen levels. Taken together, these findings suggested that octacosanol nanoemulsions have promising applications as anti-fatigue functional foods.

Peroxiredoxin-2 represses NRAS-mutated melanoma cells invasion by modulating EMT markers.

The second most common mutation in melanoma occurs in NRAS oncogene, being a more aggressive disease that has no effective approved treatment. Besides, cellular plasticity limits better outcomes of the advanced and therapy-resistant patients. Peroxiredoxins (PRDXs) control cellular processes through direct hydrogen peroxide oxidation or by redox-relaying processes. Here, we demonstrated that PRDX2 could act as a modulator of multiple EMT markers in NRAS-mutated melanomas. PRDX2 knockdown lead to phenotypic changes towards invasion in human reconstructed skin and the treatment with a PRDX mimetic (gliotoxin), decreased migration in PRDX2-deficient cells. We also confirmed the favorable clinical outcome of patients expressing PRDX2 in a large primary melanoma cohort. This study contributes to our knowledge about genes involved in phenotype switching and opens a new perspective for PRDX2 as a biomarker and target in NRAS-mutated melanomas.

Multifunctional curcumin-based polymer coating: A promising platform against bacteria, inflammation and coagulation.

The extensive use of polymers in the medical field has facilitated the development of various devices and implants, contributing to the restoration of organ function. However, despite their advantages such as biocompatibility and robustness, these materials often face challenges like bacterial contamination and subsequent inflammation, leading to implant-associated infections (IAI). Integrating implants effectively is crucial to prevent bacterial colonization and reduce inflammatory responses. To overcome these major issues, surface chemical modifications have been extensively explored. Indeed, click chemistry, and particularly, copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has emerged as a promising approach for surface functionalization without affecting material bulk properties. Curcumin, known for its diverse biological activities, suffers from low solubility and stability. To enhance its bioavailability, bioconjugation strategy has garnered attention in recent years. This study represents pioneering work in immobilizing curcumin derivative onto polyethylene terephthalate (PET) surfaces, aiming to combat bacterial adhesion, inflammation and coagulation. Before curcumin derivative bioconjugation, a fluorophore, dansyl derivative, was employed in order to monitor and determine the efficiency of the proposed methodology. Previous surface chemical modifications were required for the immobilization of both dansyl and curcumin derivatives. Ultraviolet-Visible (UV-Vis) demonstrated the amidation functionalization of PET surface. Other surface characterization techniques including X-ray Photoelectron Spectroscopy (XPS), Attenuated Total Reflectance Fourier Transformed Infrared (ATR-FTIR), Scanning Electron Microscopy (SEM) and contact angle, among others, confirmed also the conjugation of both dansyl and curcumin derivatives. On the other hand, different biological assays corroborated that curcumin derivative immobilized PET surfaces do not exhibit cytotoxicity effect. Additionally, corresponding inflammation test were performed, indicating that these polymeric surfaces do not produce inflammation and, when curcumin derivative is immobilized, they decrease the inflammation marker level (IL-6). Moreover, the bacterial growth of both Gram positive and Gram negative bacteria were measured, demonstrating that the immobilization of curcumin derivative on PET provided antibacterial properties to the material. Finally, hemolysis rate analysis and whole blood clotting assay demonstrated the antithrombogenic effect of PET-Cur surfaces as well as no hemolysis concern in the fabricated functional surfaces.

Notoginsenoside R1 attenuates ischemic heart failure by modulating MDM2/ß arrestin2-mediated ß2-adrenergic receptor ubiquitination.

ß2 adrenergic receptor (ß2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged ß2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6 J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30 mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (ß-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased ß2AR levels and decreased ß2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and ß-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between ß-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of ß2AR to improve CHF.

Dietary vitamin D3 supplementation enhances splenic NK cell activity in healthy and diabetic male mice.

Type 2 diabetes mellitus negatively affects the immune system, resulting in reduced natural killer (NK) cell activity. Vitamin D has been shown to regulate innate and adaptive immune cells. However, the effects of vitamin D on NK cells remain inconclusive, especially in the context of diabetes. We hypothesized that dietary vitamin D3 supplementation can enhance NK cell activity in diabetic mice. Therefore, we investigated the effects of dietary vitamin D3 on NK cell activity in control and diabetic mice and explored the mechanisms of NK cell activity modulation by vitamin D3. Control (CON) and diabetic mice (db/db) were randomly divided into 2 groups, then fed either a control diet (948 IU vitamin D3/kg diet, vDC) or a diet supplemented with vitamin D3 (9,477 IU vitamin D3/kg diet, vDS) for 8 weeks. Diabetic mice exhibited lower NK cell activity than control mice. The vDS group had significantly higher NK cell activity than the vDC group in both control and diabetic mice. The vDS group had a higher percentage of CD11b single-positive NK cells than the vDC group (CON-vDS 34%; db/db-vDS 30%; CON-vDC 27%; db/db-vDC 22%). The intracellular expression of splenic TGF-ß was significantly higher in the db/db group than in the CON group. Overall, vDS group had higher Bcl2 and Tbx21 mRNA expressions than the vDC group. In conclusion, the present study shows that NK cell activity is impaired under diabetic conditions, possibly due to the reduced percentage of mature NK cells. Moreover, NK activity is enhanced by dietary supplementation in both control and diabetic mice that may be associated with changes in the proportion of mature NK cells.

CAFs and T cells interplay: The emergence of a new arena in cancer combat.

The interaction between the immune system and the tumor matrix has a huge impact on the progression and treatment of cancer. This paper summarizes and discusses the crosstalk between T cells and cancer-associated fibroblasts (CAFs). CAFs can also produce inhibitors that counteract the function of T cells and promote tumor immune escape, while T cells can also engage in complex two-way interactions with CAFs through direct cell contact, the exchange of soluble factors such as cytokines, and the remodeling of the extracellular matrix. Precise targeted intervention can effectively reverse tumor-promoting crosstalk between T cells and CAFs, improve anti-tumor immune response, and provide a new perspective for cancer treatment. Therefore, it is important to deeply understand the mechanism of crosstalk between T cells and CAFs. This review aims to outline the underlying mechanisms of these interactions and discuss potential therapeutic strategies that may become fundamental tools in the treatment of cancer, especially hard-to-cure cancers.

Endoplasmic reticulum morphology regulation by RTN4 modulates neuronal regeneration by curbing luminal transport.

Cell functions rely on intracellular transport systems distributing bioactive molecules with high spatiotemporal accuracy. The endoplasmic reticulum (ER) tubular network constitutes a system for delivering luminal solutes, including Ca2+, across the cell periphery. How the ER structure enables this nanofluidic transport system is unclear. Here, we show that ER membrane-localized reticulon 4 (RTN4/Nogo) is sufficient to impose neurite outgrowth inhibition in human cortical neurons while acting as an ER morphoregulator. Improving ER transport visualization methodologies combined with optogenetic Ca2+ dynamics imaging and in silico modeling, we observed that ER luminal transport is modulated by ER tubule narrowing and dilation, proportional to the amount of RTN4. Excess RTN4 limited ER luminal transport and Ca2+ release, while RTN4 elimination reversed the effects. The described morphoregulatory effect of RTN4 defines the capacity of the ER for peripheral Ca2+ delivery for physiological releases and thus may constitute a mechanism for controlling the (re)generation of neurites.

A carrier-free, injectable, and self-assembling hydrogel based on carvacrol and glycyrrhizin exhibits high antibacterial activity and enhances healing of MRSA-infected wounds.

Inspired by glycyrrhizin's strong pharmacological activities and the directed self-assembly into hydrogels, we created a novel carrier-free, injectable hydrogel (CAR@glycygel) by combining glycyrrhizin with carvacrol (CAR), without any other chemical crosslinkers, to promote wound healing on bacteria-infected skin. CAR appeared to readily dissolve and load into CAR@glycygel. CAR@glycygel had a dense, porous, sponge structure and strong antioxidant characteristics. In vitro, it showed better antibacterial ability than free CAR. For methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, and Escherichia coli, the diameter of inhibition zone values of CAR@glycygel were 3.80 ± 0.04, 3.31 ± 0.20 and 3.12 ± 0.24 times greater, respectively, than those of free CAR. The MICs for CAR@glycygel was 156.25 µg/mL while it was 1250.00 µg/mL for free CAR to these three bacteria. Its antibacterial mechanism appeared to involve destruction of the integrity of the bacterial cell wall and biomembrane, leading to a leakage of AKP and inhibition of biofilm formation. In vivo, CAR@glycygel effectively stopped bleeding. When applied to skin wounds on rats infected with MRSA, CAR@glycygel had strong bactericidal activity and improved wound healing. The wound healing rates for CAR@glycygel were 49.59 ± 15.78 %, 93.02 ± 3.09 % and 99.02 ± 0.55 % on day 3, day 7, and day 11, respectively, which were much better than blank control and positive control groups. Mechanisms of CAR@glycygel accelerating wound healing involved facilitating epidermis remolding, promoting the growth of hair follicles, stimulating collagen deposition, mitigating inflammation, and promoting angiogenesis. Overall, CAR@glycygel showed great potential as wound dressing for infected skin wounds.