Upregulation of collagen type X alpha 1 promotes the progress of triple-negative breast cancer via Wnt/ß-catenin signaling.

Triple-negative breast cancer (TNBC) is a malignant tumor with high degree of malignancy and lack of effective target treatment. The research aims to explore the role and mechanism of X collagen alpha-1 chain protein (COL10A1 gene) in TNBC. UALCAN and Kaplan-Meier were used to detect the expression of COL10A1 and its role in the prognosis of breast cancer patients. The cells with stably expressing high levels of COL10A1 were obtained by recombinant lentivirus infection. The expression of COL10A1 in cells was temporarily downregulated by siRNA interference fragments. Real-time quantitative polymerase chain reaction and western blot analysis were utilized to detect the changes of COL10A1 mRNA and protein expression. The biological functions of the cells were evaluated by colony formation, cell counting kit-8, cell invasion and wound healing experiments. In addition, the effect of COL10A1 on angiogenesis was investigated by tube formation assay. Xenograft tumor model was used to confirm the effect of COL10A1 on tumorigenicity in vivo and multiplex fluorescent immunohistochemistry to detect multiple proteins simultaneously. The possible molecular mechanism of the function of COL10A1 was speculated through the detection of proteins in functionally related pathways. COL10A1 is highly expressed and is significantly associated with worse overall survival (OS) and recurrence-free survival (RFS) in TNBC. Overexpression of COL10A1 increased the clone formation rate and cell migration capacity of TNBC cells. In the COL10A1 overexpression group, the clone formation rates of MD-MB-231 and BT-549 cells (21.5 ± 0.62, 27.83 ± 3.72)% were significantly higher than those in the control group(15.23 ± 2.79, 19.4 ± 1.47)%, and the relative migration ratio (47.40 ± 3.09, 41.26 ± 4.33)% were higher than those in the control group (34.48 ± 2.03, 21.80 ± 1.03)%. When the expression of COL10A1 was downregulated, the ability of clone formation and wound-healing migration capacity in TNBC cells was weakened. Upregulated COL10A1 in TNBC cells generated more junctions and longer total segments between vascular endothelial cells, and promoted angiogenesis of the cells, and thus enhanced the tumorigenesis. In TNBC, it was found that COL10A1 might affect epithelial-mesenchymal transition (EMT) of the cells through Wnt/ß-catenin signaling pathway by the detection of the related pathway proteins. COL10A1 is highly expressed in TNBC, and its high expression leads to poor OS and RFS. COL10A1 may enhance TNBC cell proliferation, migration and tumor-related angiogenesis, and promote tumorigenesis in vivo via Wnt/ß-catenin signaling.

Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration.

The effective regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant clinical challenge. Traditional treatments such as autologous and allograft bone grafting have not been successful in achieving the desired outcomes, necessitating the need for innovative therapeutic approaches. Nucleic acids have attracted significant attention due to their ability to be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of nucleic acid nanotechnology offer numerous opportunities for in-cell and in vivo applications, and hold great promise for advancing the field of biomaterials. In this review, the current abilities of nucleic acid nanotechnology to be applied in bone and cartilage regeneration are summarized and insights into the challenges and future directions for the development of this technology are provided.

Improvement of the oxidative stability of cold-pressed sesame oil using products from the Maillard reaction of sesame enzymatically hydrolyzed protein and reducing sugars.

BACKGROUND: In recent years, cold-pressed oils have become more and more popular with consumers. However, their oxidative stability is low. Improving the oxidative stability of cold-pressed oils will increase their shelf life. Maillard reaction products (MRPs) have been shown to promote the oxidative stability of lipids. In this study, products from the Maillard reaction of reducing sugars and sesame enzymatically hydrolyzed protein (SEHP) were added to cold-pressed sesame oils to improve their oxidative stability. RESULTS: Three types of MRPs from reducing sugars (xylose, fructose, and glucose) and SEHP were prepared. Xylose-SEHP MRPs prepared under optimum conditions had the highest antioxidant activities among the three. The optimum conditions for xylose-SEHP were as follows: reaction temperature, 130 °C; reaction time, 180 min; pH, 6.5; and sugar/protein ratio, 10:1. The addition of xylose-SEHP MRPs at a level of 20 g kg-1 could significantly improve the oxidative stability of cold-pressed sesame oil. Besides, the addition of MRPs reduced the loss of tocopherol. The interaction of MRPs with endogenous antioxidants in the sesame oil (sesamol and tocopherol) was proved by comparison with lard. There was a synergistic increase in antioxidant activity for the combination of MRPs and sesamol and the combination of MRPs and tocopherol. CONCLUSIONS: The results provide evidence that adding certain MRPs can improve the oxidative stability of cold-pressed sesame oil. © 2019 Society of Chemical Industry.

The inhibitory effects of Qingchang Wenzhong granule on the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium-induced colitis.

BACKGROUND: Ulcerative colitis (UC) is a kind of complex immune disease, the pathogenesis of which remains elusive. Destruction of the intestinal barrier, extreme inflammation, oxidative stress, and apoptosis might play key roles in the development of UC. In previous studies, we observed that Qingchang Wenzhong granule (QCWZG) had the exact effect on the remission of UC in the clinic; however, the underlying mechanism has not been identified. This study aimed to reveal the effects of QCWZG on the intestinal physical barrier and the interactive network of inflammation, oxidative stress, and apoptosis in rats with dextran sulfate sodium (DSS)-induced colitis. METHODS: Sixty rats were randomly divided into six groups: blank group, model group, high/mild/low-dose QCWZG groups, and mesalazine group. The rats in the experimental group drank 4% DSS for 7 days and 1% DSS for the subsequent 7 days. Different medications or distilled water was supplied by intragastric administration for 7 days. The levels of colitis and indices related to inflammation, oxidative stress, and apoptosis were assessed. RESULTS: Compared with the model group, the QCWZG group (P < 0.05) demonstrated attenuated disease activity index, colonic mucosa disease index, histological lesions, and colonic weights; lower levels of inflammatory substances, such as interleukin (IL)-1α, IL-6, tumor necrosis factor-α, and myeloperoxidase; lower levels of malondialdehyde; and increased levels of superoxide dismutase and glutathione peroxidase. The QCWZG group also demonstrated elevated expression of Bcl-2 and occluding but downregulated db expression of Bax and caspase 3 in the colon. CONCLUSION: QCWZG could relieve rats with DSS-induced colitis from UC symptoms by improving the intestinal physical barrier, which resists the interactive network of inflammation, oxidative stress, apoptosis, and their overactivated interactions.

The effect of Heweijiangni-decoction on esophageal morphology in a rat model of OVA-induced visceral hypersensitivity followed by acid exposure.

Heweijiangni decoction (HWJND) is an effective traditional Chinese medicine prescription in clinical treatment of nonerosive reflux disease (NERD). Esophageal hypersensitivity and acid contribute to the disease. However, the exact underlying mechanism of action remains unclear. In this study, we observed the effect of HWJND on esophageal morphology in a rat model of ovalbumin (OVA)-induced visceral hypersensitivity followed by acid exposure. Esophageal morphology was assessed by measuring the extent of dilated intercellular spaces (DIS), desmosome disruption, and mitochondrial fragmentation. HWJND in low, moderate, and high doses relieved DIS and desmosome disruption in esophageal epithelium compared with model group (P<0.05 for all doses). In addition, HWJND in high dose protected mitochondria from fragmentation (P<0.05). Other findings suggest that DIS and mitochondrial fragmentation are independent events, and that omeprazole protects mitochondria. Overall, HWJND significantly resists esophageal morphology changes in OVA-induced and acid exposure rat model.

Endoplasmic reticulum stress and its effects on renal tubular cells apoptosis in ischemic acute kidney injury.

Ischemia is the most frequent cause of acute kidney injury (AKI), which is characterized by apoptosis of renal tubular cell. A common result of ischemia in AKI is dysfunction of endoplasmic reticulum (ER), which causes the protein-folding capacity to lag behind the protein-folding load. The abundance of misfolded proteins stressed the ER and results in induction of the unfolded protein response (UPR). While the UPR is an adaptive response, over time it can result in apoptosis when cells are unable to recover quickly. Recent research suggests that ER stress is a major factor in renal tubular cell apoptosis resulting from ischemic AKI. Thus, ER stress may be an important new progression factor in the pathology of ischemic AKI. In this article, we review UPR signaling, describe pathology and pathophysiology mechanisms of ischemic AKI, and highlight the dual function of ER stress on renal tubular cell apoptosis.

Corrigendum: A dynamics association study of gut barrier and microbiota in hyperuricemia.

[This corrects the article DOI: 10.3389/fmicb.2023.1287468.].

AI energized hydrogel design, optimization and application in biomedicine.

Traditional hydrogel design and optimization methods usually rely on repeated experiments, which is time-consuming and expensive, resulting in a slow-moving of advanced hydrogel development. With the rapid development of artificial intelligence (AI) technology and increasing material data, AI-energized design and optimization of hydrogels for biomedical applications has emerged as a revolutionary breakthrough in materials science. This review begins by outlining the history of AI and the potential advantages of using AI in the design and optimization of hydrogels, such as prediction and optimization of properties, multi-attribute optimization, high-throughput screening, automated material discovery, optimizing experimental design, and etc. Then, we focus on the various applications of hydrogels supported by AI technology in biomedicine, including drug delivery, bio-inks for advanced manufacturing, tissue repair, and biosensors, so as to provide a clear and comprehensive understanding of researchers in this field. Finally, we discuss the future directions and prospects, and provide a new perspective for the research and development of novel hydrogel materials for biomedical applications.

Fission cross-section measurements for the 238U(n,f)97m+gNb, 238U(n,f)133gTe and 238U(n,f)130gSb reactions induced by D-T neutrons.

In this study, we conducted measurements of the independent fission cross-sections of 238U(n, f)97m+gNb, 238U(n, f)133gTe reactions and the cumulative cross section of 238U(n, f)130gSb reactions induced by neutron at energies around 14 MeV, i.e., 14.1 ± 0.3, 14.5 ± 0.3 and 14.7 ± 0.3 MeV. The measurement results were obtained by the neutron activation method in combination with off-line γ-ray spectrometry techniques. The neutron flux was monitored on line by the accompanying α-particle from T(d, n)4He reaction, and the neutron energies were determined by the cross-section ratio of 90Zr(n, 2n)8+gZr to 93Nb(n, 2n)92mNb reactions. The independent fission cross-sections of the fission reactions were obtained by subtracting the influence of precursor nuclei or excited states. The obtained results are as follows: for 238U(n, f)97m+gNb, the independent cross sections are 1.0 ± 0.89, 0.98 ± 0.85 and 0.78 ± 0.70 mb at the specified neutron energy points. For 238U(n, f)133gTe, the independent fission cross-sections are 26.8 ± 2.8, 27.7 ± 2.9 and 20.5 ± 2.3 mb, respectively, at the same neutron energy points. As for 238U(n, f)130gSb, the obtained cumulative fission cross-sections are 5.35 ± 0.58, 5.05 ± 0.53 and 4.03 ± 0.44 mb, respectively, at the specified neutron energy points.

Boosting cartilage repair with silk fibroin-DNA hydrogel-based cartilage organoid precursor.

Osteoarthritis (OA), a common degenerative disease, is characterized by high disability and imposes substantial economic impacts on individuals and society. Current clinical treatments remain inadequate for effectively managing OA. Organoids, miniature 3D tissue structures from directed differentiation of stem or progenitor cells, mimic native organ structures and functions. They are useful for drug testing and serve as active grafts for organ repair. However, organoid construction requires extracellular matrix-like 3D scaffolds for cellular growth. Hydrogel microspheres, with tunable physical and chemical properties, show promise in cartilage tissue engineering by replicating the natural microenvironment. Building on prior work on SF-DNA dual-network hydrogels for cartilage regeneration, we developed a novel RGD-SF-DNA hydrogel microsphere (RSD-MS) via a microfluidic system by integrating photopolymerization with self-assembly techniques and then modified with Pep-RGDfKA. The RSD-MSs exhibited uniform size, porous surface, and optimal swelling and degradation properties. In vitro studies demonstrated that RSD-MSs enhanced bone marrow mesenchymal stem cells (BMSCs) proliferation, adhesion, and chondrogenic differentiation. Transcriptomic analysis showed RSD-MSs induced chondrogenesis mainly through integrin-mediated adhesion pathways and glycosaminoglycan biosynthesis. Moreover, in vivo studies showed that seeding BMSCs onto RSD-MSs to create cartilage organoid precursors (COPs) significantly enhanced cartilage regeneration. In conclusion, RSD-MS was an ideal candidate for the construction and long-term cultivation of cartilage organoids, offering an innovative strategy and material choice for cartilage regeneration and tissue engineering.

Heterogeneous DNA hydrogel loaded with Apt02 modified tetrahedral framework nucleic acid accelerated critical-size bone defect repair.

Segmental bone defects, stemming from trauma, infection, and tumors, pose formidable clinical challenges. Traditional bone repair materials, such as autologous and allogeneic bone grafts, grapple with limitations including source scarcity and immune rejection risks. The advent of nucleic acid nanotechnology, particularly the use of DNA hydrogels in tissue engineering, presents a promising solution, attributed to their biocompatibility, biodegradability, and programmability. However, these hydrogels, typically hindered by high gelation temperatures (∼46 °C) and high construction costs, limit cell encapsulation and broader application. Our research introduces a novel polymer-modified DNA hydrogel, developed using nucleic acid nanotechnology, which gels at a more biocompatible temperature of 37 °C and is cost-effective. This hydrogel then incorporates tetrahedral Framework Nucleic Acid (tFNA) to enhance osteogenic mineralization. Furthermore, considering the modifiability of tFNA, we modified its chains with Aptamer02 (Apt02), an aptamer known to foster angiogenesis. This dual approach significantly accelerates osteogenic differentiation in bone marrow stromal cells (BMSCs) and angiogenesis in human umbilical vein endothelial cells (HUVECs), with cell sequencing confirming their targeting efficacy, respectively. In vivo experiments in rats with critical-size cranial bone defects demonstrate their effectiveness in enhancing new bone formation. This innovation not only offers a viable solution for repairing segmental bone defects but also opens avenues for future advancements in bone organoids construction, marking a significant advancement in tissue engineering and regenerative medicine.

Targeted and responsive biomaterials in osteoarthritis.

Osteoarthritis (OA) is a degenerative disease characterized by loss of articular cartilage and chronic inflammation, involving multiple cellular dysfunctions and tissue lesions. The non-vascular environment and dense cartilage matrix in the joints tend to block drug penetration, resulting in low drug bioavailability. There is a desire to develop safer and more effective OA therapies to meet the challenges of an aging world population in the future. Biomaterials have achieved satisfactory results in improving drug targeting, prolonging the duration of action, and achieving precision therapy. This article reviews the current basic understanding of the pathological mechanisms and clinical treatment dilemmas of OA, summarizes and discusses the advances for different kinds of targeted and responsive biomaterials in OA, seeking to provide new perspectives for the treatment of OA. Subsequently, limitations and challenges in clinical translation and biosafety are analyzed to guide the development of future therapeutic strategies for OA. As the need for precision medicine rises over time, emerging multifunctional biomaterials based on tissue targeting and controlled release will become an irreplaceable part of OA management.

The risk factors associated with traumatic subdural effusion for patients with traumatic brain injury who did not undergo decompressive craniectomy.

PURPOSE: The main aim of this study was to investigate the risk factors of traumatic subdural effusion (TSE) development in traumatic brain injury (TBI) patients who did not undergo decompressive craniectomy (DC). METHODS: This is a retrospective study based on a database of patients treated in a single institution from January 2020 to January 2022. The clinical and demographic characteristics of the enrolled patients, including gender, age, Glasgow Coma Scale score at admission, characteristics of the initial CT scan on admission, mechanism of injury and the mannitol treatment were recorded retrospectively. RESULTS: Two hundred fifty-four patients with TBI who did not receive DC were enrolled in this study. Among them, 78 (30.71%) patients were assigned to the TSE group, while 176 patients (69.29%) without TSE were assigned to the control group. Univariate analysis showed that patients in the TSE group were more likely to be male (p = 0.019), older (p < 0.001), have a subarachnoid haemorrhage (p = 0.016) and have a basal cistern haemorrhage (p = 0.014). Logistic regression analysis identified that older age (odds ratio [OR] = 1.056, p < 0.001), presence of subarachnoid haemorrhage (OR = 2.022, p = 0.018) and presence of basal cistern haemorrhage (OR = 2.861, p = 0.027) were risk factors independently associated with the development of TSE. CONCLUSION: Our results showed that older age, presence of subarachnoid haemorrhage and presence of basal cistern haemorrhage were risk factors independently associated with the development of TSE for TBI patients without DC.

Optimization design of the portable cylindrical water injection multilayer neutron spectrometer.

The currently widely used multi-sphere neutron spectrometers still have many drawbacks, including complex design and processing, the need for multiple moderating spheres, high costs, large volumes, and complicated measurement procedures. This work proposes the portable cylindrical water injection multilayer neutron spectrometer (CWNS) as a promising alternative based on water pumping injection. The structure of CWNS consists of a central thermal neutron detector and a surrounding 6-layer of coaxial cylindrical water bags with varying diameters. During non-measurement periods, this CWNS is convenient to carry due to the absence of the need to inject moderating water. To optimize the CWNS design, we employed FLUKA simulation software to study and refine various parameters, including the thickness of the water bag, the material composition of the water bag, and the parameters of the supporting column. We finally achieved an optimized design. Specifically, the water bag of the CWNS is constructed using a 0.3 mm thick polyethylene film. The supporting column for the water bag is made of aluminum, providing stability and support to the overall structure. These optimized design parameters determine the specific size and configuration of the CWNS. The CWNS offers the benefits of convenient carrying, simplified processing, cost-effectiveness, and straightforward measurement. It has a promising potential use for the directional neutron dose monitoring.

A dynamics association study of gut barrier and microbiota in hyperuricemia.

Introduction: The intricate interplay between gut microbiota and hyperuricemia remains a subject of growing interest. However, existing studies only provided snapshots of the gut microbiome at single time points, the temporal dynamics of gut microbiota alterations during hyperuricemia progression and the intricate interplay between the gut barrier and microbiota remain underexplored. Our investigation revealed compelling insights into the dynamic changes in both gut microbiota and intestinal barrier function throughout the course of hyperuricemia. Methods: The hyperuricemia mice (HY) were given intragastric administration of adenine and potassium oxalate. Gut microbiota was analyzed by 16S rRNA sequencing at 3, 7, 14, and 21 days after the start of the modeling process. Intestinal permeability as well as LPS, TNF-α, and IL-1ß levels were measured at 3, 7, 14, and 21 days. Results: We discovered that shifts in microbial community composition occur prior to the onset of hyperuricemia, key bacterial Bacteroidaceae, Bacteroides, and Blautia exhibited reduced levels, potentially fueling microbial dysbiosis as the disease progresses. During the course of hyperuricemia, the dynamic fluctuations in both uric acid levels and intestinal barrier function was accompanied with the depletion of key beneficial bacteria, including Prevotellaceae, Muribaculum, Parabacteroides, Akkermansia, and Bacteroides, and coincided with an increase in pathogenic bacteria such as Oscillibacter and Ruminiclostridium. This microbial community shift likely contributed to elevated lipopolysaccharide (LPS) and pro-inflammatory cytokine levels, ultimately promoting metabolic inflammation. The decline of Burkholderiaceae and Parasutterella was inversely related to uric acid levels, Conversely, key families Ruminococcaceae, Family_XIII, genera Anaeroplasma exhibited positive correlations with uric acid levels. Akkermansiaceae and Bacteroidaceae demonstrating negative correlations, while LPS-containing microbiota such as Desulfovibrio and Enterorhabdus exhibited positive correlations with intestinal permeability. Conclusion: In summary, this study offers a dynamic perspective on the complex interplay between gut microbiota, uric acid levels, and intestinal barrier function during hyperuricemia progression. Our study suggested that Ruminiclostridium, Bacteroides, Akkermansiaceae, Bilophila, Burkholderiaceae and Parasutterella were the key bacteria that play vital rols in the progress of hyperuricemia and compromised intestinal barrier, which provide a potential avenue for therapeutic interventions in hyperuricemia.

Selection and identification of a novel ssDNA aptamer targeting human skeletal muscle.

Skeletal muscle disorders have posed great threats to health. Selective delivery of drugs and oligonucleotides to skeletal muscle is challenging. Aptamers can improve targeting efficacy. In this study, for the first time, the human skeletal muscle-specific ssDNA aptamers (HSM01, etc.) were selected and identified with Systematic Evolution of Ligands by Exponential Enrichment (SELEX). The HSM01 ssDNA aptamer preferentially interacted with human skeletal muscle cells in vitro. The in vivo study using tree shrews showed that the HSM01 ssDNA aptamer specifically targeted human skeletal muscle cells. Furthermore, the ability of HSM01 ssDNA aptamer to target skeletal muscle cells was not affected by the formation of a disulfide bond with nanoliposomes in vitro or in vivo, suggesting a potential new approach for targeted drug delivery to skeletal muscles via liposomes. Therefore, this newly identified ssDNA aptamer and nanoliposome modification could be used for the treatment of human skeletal muscle diseases.

Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression.

Abnormal subchondral bone remodeling featured by overactivated osteoclastogenesis leads to articular cartilage degeneration and osteoarthritis (OA) progression, but the mechanism is unclear. We used lymphocyte cytosolic protein 1 (Lcp1) knockout mice to suppress subchondral osteoclasts in a mice OA model with anterior cruciate ligament transection (ACLT), and Lcp1-/- mice showed decreased bone remodeling in subchondral bone and retarded cartilage degeneration. For mechanisms, the activated osteoclasts in subchondral bone induced type-H vessels and elevated oxygen concentration, which ubiquitylated hypoxia-inducible factor 1 alpha subunit (HIF-1α) in chondrocytes and led to cartilage degeneration. Lcp1 knockout impeded angiogenesis, which maintained hypoxia environment in joints and delayed the OA progression. Stabilization of HIF-1α delayed cartilage degeneration, and knockdown of Hif1a abolished the protective effects of Lcp1 knockout. Last, we showed that Oroxylin A, an Lcp1-encoded protein l-plastin (LPL) inhibitor, could alleviate OA progression. In conclusion, maintaining hypoxic environment is an attractive strategy for OA treatment.

Exosomal myeloperoxidase as a biomarker of deep venous thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) often occurs following major orthopedic surgery. In this study, we investigated specific exosomal proteins as potential diagnostic biomarkers of DVT. METHODS: Proteomic analysis of exosomes from four DVT patients and healthy controls (n=4) was performed by mass spectrometry. The model animals were evaluated at 1 inferior vena cava ligation [(IVCL)-1D], 3 (IVCL-3D), and 7 (IVCL-7D) days after IVCL. Endothelial cells in the thrombus segment were examined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and hematoxylin and eosin (HE) staining. Myeloperoxidase (MPO) expression in the damaged vessel was detected by immunofluorescence staining. Exosomes were co-cultured with human umbilical vein endothelial cells (HUVECs) and cell proliferation was estimated using Cell Counting Kit-8 (CCK-8) assays. RESULTS: A total of 78 differentially expressed proteins (DEPs; 38 downregulated and 40 upregulated) were identified in the DVT group. In the rat DVT model, endothelial cells were damaged continuously after thrombosis, with the most serious injury in the IVCL-3D group, after which signs of endothelial repair were apparent. The IVCL-1D group showed the highest levels of vascular endothelial cell apoptosis and MPO increased sharply in the IVCL-1D and IVCL-3D groups, but had almost disappeared in the IVCL-7D group. In co-culture, plasma exosomes isolated from DVT model rats were efficiently absorbed by HUVECs, with markedly lower HUVECs growth and higher levels of apoptosis in the IVCL-1D and IVCL-3D groups compared with the control group. CONCLUSIONS: Our findings suggest that exosomes may be involved in endothelial cell injury during DVT. The exosomal protein MPO is a potential biomarker of early stage DVT.

Bacterial extracellular vesicles-based therapeutic strategies for bone and soft tissue tumors therapy.

Bone and soft tissue tumors are complex mesenchymal neoplasms that seriously endanger human health. Over the past decade, the relationship between microorganisms and human health and diseases is getting more attention. The extracellular vesicles derived from bacteria have been shown to regulate bacterial-host cell communication by transferring their contents, including nucleic acids, proteins, metabolites, lipopolysaccharides, and peptidoglycans. Bacteria extracellular vesicles (BEVs) are promising lipid-bilayer nanocarriers for the treatment of many diseases due to their low toxicity, drug loading capacity, ease of modification and industrialization. Specially, BEVs-based cancer therapy has attracted much attention because of their ability to effectively stimulate immune responses. In this review, we provide an overview of the biogenesis, composition, isolation, classification, and internalization of BEVs. We then comprehensively summarize the sources of BEVs in cancer therapy and the BEVs-related cancer treatment strategies. We further highlight the great potential of BEVs in bone and soft tissue tumors. Finally, we conclude the major advantages and challenges of BEVs-based cancer therapy. We believe that the comprehensive understanding of BEVs in the field of cancer therapy will generate innovative solutions to bone and soft tissue tumors and achieve clinical applications.

The role and mechanisms of gut microbiota in diabetic nephropathy, diabetic retinopathy and cardiovascular diseases.

Type 2 diabetes mellitus (T2DM) and T2DM-related complications [such as retinopathy, nephropathy, and cardiovascular diseases (CVDs)] are the most prevalent metabolic diseases. Intriguingly, overwhelming findings have shown a strong association of the gut microbiome with the etiology of these diseases, including the role of aberrant gut bacterial metabolites, increased intestinal permeability, and pathogenic immune function affecting host metabolism. Thus, deciphering the specific microbiota, metabolites, and the related mechanisms to T2DM-related complications by combined analyses of metagenomics and metabolomics data can lead to an innovative strategy for the treatment of these diseases. Accordingly, this review highlights the advanced knowledge about the characteristics of the gut microbiota in T2DM-related complications and how it can be associated with the pathogenesis of these diseases. Also, recent studies providing a new perspective on microbiota-targeted therapies are included.