Effect of polyethylene terephthalate plastics on nitrogen, sulphur and chlorine contaminants via sludge pyrolysis and Pb/Cu adsorption properties of biochar.

Pyrolysis is an effective process for disposing of municipal sewage sludge (SS). Plastics can affect the SS pyrolysis behaviour and pyrolysis products due to their low ash and high hydrocarbon ratio. The secondary pollutants from the pyrolysis process may also be affected. Therefore, polyethylene terephthalate (PET), a typical plastic, was chosen to investigate the release characteristics of pollutants containing nitrogen, sulphur, and chlorine via SS pyrolysis, and the changes of biochar to adsorb two typical heavy metals, Pb and Cu. The pyrolysis of PET plastics facilitates the migration of N toward solid and liquid-phase products, S and Cl to the gas-phase products via pyrolysis. Oxygenated compounds of pyrolytic volatiles decreased from 38.18% to 28.43%, concurrently promoting the formation of phenolic compounds. The co-pyrolysis improved the quality of biochar and the ability to adsorb Pb and Cu. This systematic study can provide some support for the further improvement of SS pyrolysis technology, and will also be beneficial for subsequent applications.

"Coir Raincoat"-Boosted Biomimetic Hydrogel for Efficient Solar Desalination and Wastewater Purification.

Solar-driven interfacial evaporation is an efficient method for purifying contaminated or saline water. Nonetheless, the suboptimal design of the structure and composition still necessitates a compromise between evaporation rate and service life. Therefore, achieving efficient production of clean water remains a key challenge. Here, a biomimetic dictyophora hydrogel based on loofah/carbonized sucrose@ZIF-8/polyvinyl alcohol is demonstrated, which can serve as an independent solar evaporator for clean water recovery. This special structural design achieves effective thermal positioning and minimal heat loss, while reducing the actual enthalpy of water evaporation. The evaporator achieves a pure water evaporation rate of 3.88 kg m-2 h-1 and a solar-vapor conversion efficiency of 97.16% under 1 sun irradiation. In comparison, the wastewater evaporation rate of the evaporator with ZIF-8 remains at 3.85 kg m-2 h-1 for 30 days, which is 16.3% higher than the light irradiation without ZIF-8. Equally important, the evaporator also showcases the capability to cleanse water from diverse sources of contaminants, including those with small molecules, oil, heavy metal ions, and bacteria, greatly improving the lifespan of the evaporator.

RNA sequencing reveals the potential mechanism of exercise preconditioning for cerebral ischemia reperfusion injury in rats.

INTRODUCTION: Cerebral ischemia reperfusion injury (CIRI) often leads to deleterious complications after stroke patients receive reperfusion therapy. Exercise preconditioning (EP) has been reported to facilitate brain function recovery. We aim to explore the specific mechanism of EP in CIRI. METHODS: Sprague-Dawley rats were randomized into Sham, middle cerebral artery occlusion (MCAO), and EP groups (n = 11). The rats in the EP group received adaptive training for 3 days (10 m/min, 20 min/day, with a 0° incline) and formal training for 3 weeks (6 days/week, 25 m/min, 30 min/day, with a 0° incline). Then, rats underwent MCAO surgery to establish CIRI models. After 48 h, neurological deficits and cerebral infarction of the rats were measured. Neuronal death and apoptosis in the cerebral cortices were detected. Furthermore, RNA sequencing was conducted to investigate the specific mechanism of EP on CIRI, and qPCR and Western blotting were further applied to confirm RNA sequencing results. RESULTS: EP improved neurological deficit scores and reduced cerebral infarction in MCAO rats. Additionally, pre-ischemic exercise also alleviated neuronal death and apoptosis of the cerebral cortices in MCAO rats. Importantly, 17 differentially expressed genes (DEGs) were identified through RNA sequencing, and these DEGs were mainly enriched in the HIF-1 pathway, cellular senescence, proteoglycans in cancer, and so on. qPCR and Western blotting further confirmed that EP could suppress TIMP1, SOCS3, ANGPTL4, CDO1, and SERPINE1 expressions in MCAO rats. CONCLUSION: EP can improve CIRI in vivo, the mechanism may relate to TIMP1 expression and HIF-1 pathway, which provided novel targets for CIRI treatment.

The Roles of Exosomes in Regulating Hair Follicle Growth.

Alopecia is considered a widespread yet troubling health issue, with limited treatment options. As membranous structures derived from cells carrying proteins, nucleic acids and lipids, exosomes functionally medicate intercellular communication and alter the responses of recipient cells, resulting in disease restraint or promotion. Exosomes have broad prospects in diagnosis and treatment of diseases. Studies using animal models and at the cellular level have clearly shown that exosomes from several types of cells, including dermal papilla cells and mesenchymal stem cells, have a notable capacity to promote hair growth, suggesting that exosomes may provide a new option to treat alopecia. Here, we present a thorough review of the most recent progress in the application of exosomes to hair growth.

Investigating the impact of schizophrenia traits on attention: the role of the theta band in a modified Posner cueing paradigm.

Joint attention is an indispensable tool for daily communication. Abnormalities in joint attention may be a key reason underlying social impairment in schizophrenia spectrum disorders. In this study, we aimed to explore the attentional orientation mechanism related to schizotypal traits in a social situation. Here, we employed a Posner cueing paradigm with social attentional cues. Subjects needed to detect the location of a target that is cued by gaze and head orientation. The power in the theta frequency band was used to examine the attentional process in the schizophrenia spectrum. There were four main findings. First, a significant association was found between schizotypal traits and attention orientation in response to invalid gaze cues. Second, individuals with schizotypal traits exhibited significant activation of neural oscillations and synchrony in the theta band, which correlated with their schizotypal tendencies. Third, neural oscillations and synchrony demonstrated a synergistic effect during social tasks, particularly when processing gaze cues. Finally, the relationship between schizotypal traits and attention orientation was mediated by neural oscillations and synchrony in the theta frequency band. These findings deepen our understanding of the impact of theta activity in schizotypal traits on joint attention and offer new insights for future intervention strategies.

The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis.

Psoriasis is an intractable immune-mediated disorder that disrupts the skin barrier. While studies have dissected the mechanism by which immune cells directly regulate epidermal cell proliferation, the involvement of dermal fibroblasts in the progression of psoriasis remains unclear. Here, we identified that signals from dendritic cells (DCs) that migrate to the dermal-epidermal junction region enhance dermal stiffness by increasing extracellular matrix (ECM) expression, which further promotes basal epidermal cell hyperproliferation. We analyzed cell-cell interactions and observed stronger interactions between DCs and fibroblasts than between DCs and epidermal cells. Using single-cell RNA (scRNA) sequencing, spatial transcriptomics, immunostaining, and stiffness measurement, we found that DC-secreted LGALS9 can be received by CD44+ dermal fibroblasts, leading to increased ECM expression that creates a stiffer dermal environment. By employing mouse psoriasis and skin organoid models, we discovered a mechano-chemical signaling pathway that originates from DCs, extends to dermal fibroblasts, and ultimately enhances basal cell proliferation in psoriatic skin.

Long-Term Stimulation of the Left Dorsal Branch of the Thoracic Nerve Improves Ventricular Electrical Remodeling in a Canine Model of Chronic Myocardial Infarction.

PURPOSE: To evaluate the ventricular electrophysiologic effects of long-term stimulation of the left dorsal branch of thoracic nerve (LDTN) derived from the left stellate ganglion (LSG) in a canine model of chronic myocardial infarction (MI). METHODS: Seventeen adult male beagles were randomly divided into three groups: the sham group (sham operated, n = 6), the MI group (n = 6), and the MI + LDTN group (MI plus LDTN stimulation, n = 5). The canine model of chronic MI was induced by the occlusion of the left anterior descending artery (LADO). The LDTN was separated and intermittently stimulated immediately after LADO for 2 months. The heart rate variability (HRV) analysis, in vivo electrophysiology, the evaluation of LSG function and neural activity, histological staining, and western blotting (WB) assay were performed to evaluate the effect of LDTN stimulation on the heart. RESULTS: The canine MI model was successfully established by LADO, and the LDTN was separated and stimulated immediately after LADO. The HRV analysis showed that LDTN stimulation reversed the increased LF value and LF/HF ratio of the MI group. LDTN stimulation prolonged the shortening ERP and APD90, decreased the dispersion of ERP and APD90, and increased the VFT. Additionally, LDTN stimulation inhibits the LSG function and neural activity. Furthermore, LDTN stimulation suppressed the activation of Wnt/ß-catenin signaling, which contributed to the LSG neuronal apoptosis by upregulation of pro-apoptotic Bax and downregulation of anti-apoptotic Bcl-2. CONCLUSION: LDTN stimulation could attenuate cardiac sympathetic remodeling and improve ventricular electrical remodeling, which may be mediated by suppressing the activated Wnt/ß-catenin signaling pathway and then promoting the LSG neuronal apoptosis.

Sodium selenite attenuates inflammatory response and oxidative stress injury by regulating the Nrf2/ARE pathway in contrast-induced acute kidney injury in rats.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is an acute renal complication that occurs after intravascular contrast agent administration. Sodium selenite (SS) is an inorganic source of Se and has potent antioxidant properties. This study intends to examine its anti-inflammatory and antioxidant effects in CI-AKI. METHODS: A rat CI-AKI model was established with the pretreatment of SS (0.35 mg/kg). Hematoxylin-eosin staining was employed for histopathological analysis of rat kidney specimens. Biochemical analysis was conducted for renal function detection. Tissue levels of oxidative stress-related markers were estimated. Reverse transcription-quantitative polymerase chain reaction revealed the mRNA levels of proinflammatory cytokines. Western blotting showed the Nrf2 signaling-related protein expression in the rat kidney. RESULTS: SS administration alleviated the renal pathological changes and reduced the serum levels of serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, cystatin C, and urinary level of kidney injury molecule-1 in CI-AKI rats. SS attenuated oxidative stress and inflammatory response in CI-AKI rat kidney tissues. SS activated the Nrf2 signaling transduction in the renal tissues of rats with CI-AKI. CONCLUSION: SS ameliorates CI-AKI in rats by reducing oxidative stress and inflammation via the Nrf2 signaling.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Gegen Qinlian decoction inhibited M1 macrophage polarization and ulcerative colitis progression through regulating histone lactylation.

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the bowels. Gegen Qinlian decoction (GQD) has been widely used in the therapy of gastrointestinal diseases. We investigated the protective impacts and mechanism of GQD against UC. To establish the UC model, dextran sulfate sodium (DSS) was utilized. The disease activity index (DAI), colon length and colonic pathology were assessed to examine the impacts of GQD on UC. The level of pan-lysine lactylation (Pan kla) and specific sites were detected using western blot. Then, the inflammatory factors and the oxidative stress parameters were measured via the corresponding kits, respectively. Our findings demonstrated that GQD suppressed the lactate generation and LDH activity. The western blot revealed that GQD inhibited the expression of Pan kla and specific sites of H3K18la, H3K23la, H4K8la, and H4K12la. Furthermore, the suppressive effects on inflammation and oxidative stress caused by GQD were counteracted upon the exogenous lactate. GQD suppressed the phenotypic differentiation of M1 macrophages by reducing the expression of M1 markers, which was also reversed by exogenous lactate. In conclusion, GQD effectively suppressed UC progression through histone lactylation. Our results broadened the theoretical basis for the clinical use of GQD.

Efficient enhancement of low-rank tensor completion via thin QR decomposition.

Low-rank tensor completion (LRTC), which aims to complete missing entries from tensors with partially observed terms by utilizing the low-rank structure of tensors, has been widely used in various real-world issues. The core tensor nuclear norm minimization (CTNM) method based on Tucker decomposition is one of common LRTC methods. However, the CTNM methods based on Tucker decomposition often have a large computing cost due to the fact that the general factor matrix solving technique involves multiple singular value decompositions (SVDs) in each loop. To address this problem, this article enhances the method and proposes an effective CTNM method based on thin QR decomposition (CTNM-QR) with lower computing complexity. The proposed method extends the CTNM by introducing tensor versions of the auxiliary variables instead of matrices, while using the thin QR decomposition to solve the factor matrix rather than the SVD, which can save the computational complexity and improve the tensor completion accuracy. In addition, the CTNM-QR method's convergence and complexity are analyzed further. Numerous experiments in synthetic data, real color images, and brain MRI data at different missing rates demonstrate that the proposed method not only outperforms in terms of completion accuracy and visualization, but also conducts more efficiently than most state-of-the-art LRTC methods.

3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population.

To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.

Raspberry Ketone Attenuates Hepatic Fibrogenesis and Inflammation via Regulating the Crosstalk of FXR and PGC-1α Signaling.

Hepatic fibrosis is a compensatory response to chronic liver injury and inflammation, and dietary intervention is recommended as one of the fundamental prevention strategies. Raspberry ketone (RK) is an aromatic compound first isolated from raspberry and widely used to prepare food flavors. The current study investigated the hepatoprotection and potential mechanism of RK against hepatic fibrosis. In vitro, hepatic stellate cell (HSC) activation was stimulated with TGF-ß and cultured with RK, farnesoid X receptor (FXR), or peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) agonist or inhibitor, respectively. In vivo, C57BL/6 mice were injected intraperitoneally with thioacetamide (TAA) at 100/200 mg/kg from the first to the fifth week. Mice were intragastrically administrated with RK or Cur once a day from the second to the fifth week. In activated HSCs, RK inhibited extracellular matrix (ECM) accumulation, inflammation, and epithelial-mesenchymal transition (EMT) process. RK both activated FXR/PGC-1α and regulated their crosstalk, which were verified by their inhibitors and agonists. Deficiency of FXR or PGC-1α also attenuated the effect of RK on the reverse of activated HSCs. RK also decreased serum ALT/AST levels, liver histopathological change, ECM accumulation, inflammation, and EMT in mice caused by TAA. Double activation of FXR/PGC-1α might be the key targets for RK against hepatic fibrosis. Above all, these discoveries supported the potential of RK as a novel candidate for the dietary intervention of hepatic fibrosis.

Asymmetric total synthesis of polycyclic xanthenes and discovery of a WalK activator active against MRSA.

The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.

Cerebrospinal fluid mesencephalic astrocyte-derived neurotrophic factor: A moderating effect on sleep time and cognitive function.

BACKGROUND: Sleeping late has been associated with cognitive impairment, and insufficient sleep can affect the secretion of feeding-related cytokines. Feeding-related cytokines may contribute to cognitive deficits resulting from delayed bedtime. Glial cell line-derived neurotrophic factor (GDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF), which are feeding-related neurotrophic factors, have been associated with improved cognitive function and neuroprotective abilities. Enhanced expression of GDNF and MANF is linked to increased energy expenditure and hyperphagia, respectively. AIMS: This study aimed to investigate the association between cerebrospinal fluid (CSF) GDNF, MANF, cognition, and sleep time and to explore the moderating effects of GDNF and MANF on cognitive impairment in individuals who sleep late. METHOD: This cross-sectional study included participants (mean age 31.76 ± 10.22 years) who were categorized as ≤23 o'clock sleepers (n = 66) and >23 o'clock sleepers (n = 125) based on sleep time. Cognition was assessed using Montreal Cognitive Assessment (MoCA), and GDNF and MANF levels in CSF were measured. RESULTS: MANF may play a moderating role in the relationship between sleep time and cognition (R2 = 0.06, ß = 0.59, p = 0.031). Age showed a negative correlation with MoCA scores (R2 = 0.08, ß = -0.18), while education exhibited a positive correlation (ß = 0.17, both p < 0.05). Only ≤23 o'clock sleepers exhibited a negative correlation between MANF levels and BMI (r = -0.35, p = 0.005). CONCLUSIONS: This study provides hitherto undocumented evidence of the potential protective effect of CSF MANF on cognitive impairment of late sleepers, which suggests that maintaining a regular sleep schedule may contribute to cognition and overall health, with MANF playing a role in this process.

circADAMTS6 via stabilizing CAMK2A is involved in smoking-induced emphysema through driving M2 macrophage polarization.

Cigarette smoke (CS), an indoor environmental pollutant, is a prominent risk factor for emphysema, which is a pathological feature of chronic obstructive pulmonary disease (COPD). Emerging function of circRNAs in immune responses and disease progression shed new light to explore the pathogenesis of emphysema. In this research, we demonstrated, by single-cell RNA sequencing (scRNAseq), that the ratio of M2 macrophages were increased in lung tissues of humans and mice with smoking-related emphysema. Further, our data showed that circADAMTS6 was associated with cigarette smoke extract (CSE)-induced M2 macrophage polarization. Mechanistically, in macrophages, circADAMTS6 stabilized CAMK2A mRNA via forming a circADAMTS6/IGF2BP2/CAMK2A RNA-protein ternary complex to activate CREB, which drives M2 macrophage polarization and leads to emphysema. In addition, in macrophages of mouse lung tissues, downregulation of circADAMTS6 reversed M2 macrophage polarization, the proteinase/anti-proteinase imbalance, and the elastin degradation, which protecting against CS-induced emphysema. Moreover, for macrophages and in a model with co-cultured lung organoids, the target of circADAMTS6 restored the growth of lung organoids compared to CSE-treated macrophages. Our results also demonstrated that, for smokers and COPD smokers, elevation of circADAMTS6 negatively correlated with lung function. Overall, this study reveals a novel mechanism for circADAMTS6-driven M2 macrophage polarization in smoking-related emphysema and postulates that circADAMTS6 could serve as a diagnostic and therapeutic marker for smoking-related emphysema.

Paeoniflorin regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in oxidative stressed melanocytes.

BACKGROUND: The adhesive properties of vitiligo melanocytes have decreased under oxidative stress., cytoskeleton proteins can control cell adhesion. Paeoniflorin (PF) was proved to resist hydrogen peroxide (H2O2)-induced oxidative stress in melanocytes via nuclear factorE2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. OBJECTIVES: This study was to investigate whether PF exerts anti-oxidative effect through influencing cytoskeleton markers or potential signaling pathway. METHODS: Human Oxidative Stress Plus array was used to identify the differentially expressed genes between H2O2 + PF group and H2O2 only group, in PIG1 and PIG3V melanocyte cell lines respectively. Western blotting was used to verify the PCR array results and to test the protein expression levels of cytoskeleton markers including Ras homolog family member A (RhoA), Rho-associated kinase 1 (ROCK1) and antioxidative marker Nrf2. Small interfering RNA was used to knock down PDZ and LIM domain 1 (PDLIM1). RESULTS: PF increased the expressions of PDLIM1, RhoA and ROCK1 in H2O2-induced PIG1, in contrast, decreased the expressions of PDLIM1 and ROCK1 in H2O2-induced PIG3V. Knockdown of PDLIM1 increased the expressions of RhoA and Nrf2 in PF-pretreated H2O2-induced PIG1, and ROCK1 and Nrf2 in PF-pretreated H2O2-induced PIG3V. CONCLUSIONS: PF regulates RhoA/ROCK1 and Nrf2 pathways in PDLIM1-dependent or independent manners in H2O2-induced melanocytes. In PIG1, PF promotes PDLIM1 to inhibit RhoA/ROCK1 pathway or activates Nrf2/HO-1 pathway, separately. In PIG3V, PF directly downregulates ROCK1 in PDLIM1-independent manner or upregulates Nrf2 dependent of PDLIM1.

Revolutionizing cancer treatment: Harnessing the power of terrestrial microbial polysaccharides.

Cancer treatment faces numerous challenges, such as inadequate drug targeting, steep price tags, grave toxic side effects, and limited therapeutic efficacy. Therefore, there is an urgent need for a safe and effective new drug to combat cancer. Microbial polysaccharides, complex and diverse biological macromolecules, exhibit significant microbial variability and uniqueness. Studies have shown that terrestrial microbial polysaccharides possess a wide range of biological activities, including immune enhancement, antioxidant properties, antiviral effects, anti-tumour potential, and hypoglycemic functions. To delve deeper into the structure-activity relationship of these land-based microbial polysaccharides against cancer, we conducted a comprehensive review and analysis of anti-cancer literature published between 2020 and 2024. The anticancer efficacy of terrestrial microbial polysaccharides is influenced by multiple factors, including the microbial species, existing form, chemical structure, and polysaccharide purity. According to the literature, an optimal molecular weight and good water solubility are essential for demonstrating anticancer activity. Furthermore, the addition of mannose and galactose has been found to significantly enhance the anticancer properties of these polysaccharides. These insights will serve as a valuable reference for future research and progress in the field of cancer drug therapy, particularly with regards to terrestrial microbial polysaccharides.

Intervention with fructooligosaccharides, Saccharomyces boulardii, and their combination in a colitis mouse model.

Objective: To examine the effects of an intervention with fructooligosaccharides (FOS), Saccharomyces boulardii, and their combination in a mouse model of colitis and to explore the mechanisms underlying these effects. Methods: The effects of FOS, S. boulardii, and their combination were evaluated in a DSS-induced mouse model of colitis. To this end, parameters such as body weight, the disease activity index (DAI), and colon length were examined in model mice. Subsequently, ELISA was employed to detect the serum levels of proinflammatory cytokines. Histopathological analysis was performed to estimate the progression of inflammation in the colon. Gas chromatography was used to determine the content of short-chain fatty acids (SCFAs) in the feces of model mice. Finally, 16S rRNA sequencing technology was used to analyze the gut microbiota composition. Results: FOS was slight effective in treating colitis and colitis-induced intestinal dysbiosis in mice. Meanwhile, S. boulardii could significantly reduced the DAI, inhibited the production of IL-1ß, and prevented colon shortening. Nevertheless, S. boulardii treatment alone failed to effectively regulate the gut microbiota. In contrast, the combined administration of FOS/S. boulardii resulted in better anti-inflammatory effects and enabled microbiota regulation. The FOS/S. boulardii combination (109 CFU/ml and 107 CFU/ml) significantly reduced the DAI, inhibited colitis, lowered IL-1ß and TNF-α production, and significantly improved the levels of butyric acid and isobutyric acid. However, FOS/S. boulardii 109 CFU/ml exerted stronger anti-inflammatory effects, inhibited IL-6 production and attenuated colon shortening. Meanwhile, FOS/S. boulardii 107 CFU/ml improved microbial regulation and alleviated the colitis-induced decrease in microbial diversity. The combination of FOS and S. boulardii significantly increased the abundance of Parabacteroides and decreased the abundance of Escherichia-Shigella. Additionally, it promoted the production of acetic acid and propionic acid. Conclusion: Compared with single administration, the combination can significantly increase the abundance of beneficial bacteria such as lactobacilli and Bifidobacteria and effectively regulate the gut microbiota composition. These results provide a scientific rationale for the prevention and treatment of colitis using a FOS/S. boulardii combination. They also offer a theoretical basis for the development of nutraceutical preparations containing FOS and S. boulardii.

A full-length glycoprotein mRNA vaccine confers complete protection against severe fever with thrombocytopenia syndrome virus, with broad-spectrum protective effects against bandaviruses.

Highly pathogenic viruses from family Phenuiviridae, which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes. IMPORTANCE: Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling in situ expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.