Disulfidptosis, A Novel Cell Death Pathway: Molecular Landscape and Therapeutic Implications.

Programmed cell death is pivotal for several physiological processes, including immune defense. Further, it has been implicated in the pathogenesis of developmental disorders and the onset of numerous diseases. Multiple modes of programmed cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis, have been identified, each with their own unique characteristics and biological implications. In February 2023, Liu Xiaoguang and his team discovered "disulfidptosis," a novel pathway of programmed cell death. Their findings demonstrated that disulfidptosis is triggered in glucose-starved cells exhibiting high expression of a protein called SLC7A11. Furthermore, disulfidptosis is marked by a drastic imbalance in the NADPH/NADP+ ratio and the abnormal accumulation of disulfides like cystine. These changes ultimately lead to the destabilization of the F-actin network, causing cell death. Given that high SLC7A11 expression is a key feature of certain cancers, these findings indicate that disulfidptosis could serve as the basis of innovative anti-cancer therapies. Hence, this review delves into the discovery of disulfidptosis, its underlying molecular mechanisms and metabolic regulation, and its prospective applications in disease treatment.

Achieving High Isotropic Figure of Merit in Cd and in Codoped Polycrystalline SnSe.

Here, we combined Cd and In codoping with a simple hydrothermal synthesis method to prepare SnSe powders composed of nanorod-like flowers. After spark plasma sintering, its internal grains inherited well the morphological features of the precursor, and the multiscale microstructure included nanorod-shaped grains, high-density dislocations, and stacking faults, as well as abundant nanoprecipitates, resulting in an ultralow thermal conductivity of 0.15 W m-1 K-1 for the synthesized material. At the same time, Cd and In synergistically regulated the electrical conductivity and Seebeck coefficient of SnSe, leading to an enhanced power factor. Among them, Sn0.94Cd0.03In0.03Se achieved a peak ZT of 1.50 parallel to the pressing direction, representing an 87.5% improvement compared with pure SnSe. Notably, the material possesses isotropic ZT values parallel and perpendicular to the pressing direction, overcoming the characteristic anisotropy in thermal performance observed in previous polycrystalline SnSe-based materials. Our results provide a new strategy for optimizing the performance of thermoelectric materials through structural engineering.

Root rot destabilizes the Sanqi rhizosphere core fungal microbiome by reducing the negative connectivity of beneficial microbes.

The stability of microbial communities, especially among core taxa, is essential for supporting plant health. However, the impacts of disease infection on the stability of rhizosphere fungal core microbiome remain largely unexplored. In this study, we delved into the effects of root rot infestation on the community structure, function, network complexity, and stability of Sanqi fungal core microbiomes, employing amplicon sequencing combined with co-occurrence network and cohesion analyses. Our investigation revealed that root rot disease led to a decrease in the α-diversity but an increase in the ß-diversity of the Sanqi fungal core microbiomes in the rhizosphere. Notably, Ilyonectria, Plectosphaerella, and Fusarium emerged as indicator species in the rhizosphere core microbiome of root rot-infected Sanqi plants, while Mortierella predominated as the dominant biomarker taxa in healthy soils. Additionally, root rot diminished the complexity and modularity of the rhizosphere networks by reducing the metrics associated with nodes, edges, degrees, and modularity. Furthermore, root rot resulted in a reduction in the proportion of negative connections in the network and the negative/positive cohesion of the entire core fungal microbiome. Particularly noteworthy was the observation that root rot infection destabilized the rhizosphere core fungal microbiome by weakening the negative connectivity associated with beneficial agents. Collectively, these results highlight the significance of the negative connectivity of beneficial agents in ensuring the stability of core microbial community.IMPORTANCERoot rot disease has been reported as the most devastating disease in the production process of artificial cultivated Sanqi ginseng, which seriously threatens the Sanqi industry. This study provides valuable insights into how root rot influences microbial relationships within the community. These findings open up opportunities for disease prevention and the promotion of plant health by regulating microbial interactions. In summary, the research sheds light on the ecological consequences of root rot on rhizosphere fungal microbiomes and offers potential strategies for managing soil-borne diseases and enhancing plant health.

CdSe Quantum Dots Enable High Thermoelectric Performance in Solution-Processed Polycrystalline SnSe.

Here, a high peak ZT of ≈2.0 is reported in solution-processed polycrystalline Ge and Cd codoped SnSe. Microstructural characterization reveals that CdSe quantum dots are successfully introduced by solution process method. Ultraviolet photoelectron spectroscopy evinces that CdSe quantum dots enhance the density of states in the electronic structure of SnSe, which leads to a large Seebeck coefficient. It is found that Ge and Cd codoping simultaneously optimizes carrier concentration and improves electrical conductivity. The enhanced Seebeck coefficient and optimization of carrier concentration lead to marked increase in power factor. CdSe quantum dots combined with strong lattice strain give rise to strong phonon scattering, leading to an ultralow lattice thermal conductivity. Consequently, high thermoelectric performance is realized in solution-processed polycrystalline SnSe by designing quantum dot structures and introducing lattice strain. This work provides a new route for designing prospective thermoelectric materials by microstructural manipulation in solution chemistry.

All-Scale Hierarchical Structuring, Optimized Carrier Concentration, and Band Manipulation Lead to Ultra-High Thermoelectric Performance in Eco-Friendly MnTe.

MnTe emerges as an enormous potential for medium-temperature thermoelectric applications due to its lead-free nature, high content of Mn in the earth's crust, and superior mechanical properties. Here, it is demonstrate that multiple valence band convergence can be realized through Pb and Ag incorporations, producing large Seebeck coefficient. Furthermore, the carrier concentration can be obviously enhance by Pb and Ag codoping, contributing to significant enhancement of power factor. Moreover, microstructural characterizations reveal that PbTe nanorods can be introduced into MnTe matrix by alloying Pb. This can modify the microstructure into all-scale hierarchical architectures (including PbTe nanorods, enhances point-defect scattering, dense dislocations and stacking faults), strongly lowering lattice thermal conductivity to a record low value of 0.376 W m-1 K-1 in MnTe system. As a result, an ultra-high ZT of 1.5 can be achieved in MnTe thermoelectric through all-scale hierarchical structuring, optimized carrier concentration, and valence band convergence, outperforming most of MnTe-based thermoelectric materials.

The Role of LMP1 in Epstein-Barr Virus-associated Gastric Cancer.

EBV promotes many cancers such as lymphoma, nasopharyngeal carcinoma, and gastric; Latent Membrane Protein 1 (LMP1) is considered to be a major oncogenic protein encoded by Epstein- Barr virus (EBV). LMP1 functions as a carcinogen in lymphoma and nasopharyngeal carcinoma, and LMP1 may also promote gastric cancer. The expression level of LMP1 in host cells is a key determinant in tumorigenesis and maintenance of virus specificity. By promoting cell immortalization and cell transformation, promoting cell proliferation, affecting immunity, and regulating cell apoptosis, LMP1 plays a crucial tumorigenic role in epithelial cancers. However, very little is currently known about LMP1 in Epstein-Barr virus-associated gastric cancer (EBVaGC); the main reason is that the expression level of LMP1 in EBVaGC is comparatively lower than other EBV-encoded proteins, such as The Latent Membrane Protein 2A (LMP2A), Epstein-Barr nuclear antigen 1 (EBNA1) and BamHI-A rightward frame 1 (BARF1), to date, there are few studies related to LMP1 in EBVaGC. Recent studies have demonstrated that LMP1 promotes EBVaGC by affecting The phosphatidylinositol 3-kinase- Akt (PI3K-Akt), Nuclear factor-kappa B (NF-κB), and other signaling pathways to regulate many downstream targets such as Forkhead box class O (FOXO), C-X-C-motif chemokine receptor (CXCR), COX-2 (Cyclooxygenase-2); moreover, the gene methylation induced by LMP1 in EBVaGC has become one of the characteristics that distinguish this gastric cancer (GC) from other types of gastric cancer and LMP1 also promotes the formation of the tumor microenvironment (TME) of EBVaGC in several ways. This review synthesizes previous relevant literature, aiming to highlight the latest findings on the mechanism of action of LMP1 in EBVaGC, summarize the function of LMP1 in EBVaGC, lay the theoretical foundation for subsequent new research on LMP1 in EBVaGC, and contribute to the development of novel LMP1-targeted drugs.

The complex of tannic acid and cetylpyridinium chloride: An antibacterial and stain-removal cleaner for aligners.

INTRODUCTION: Effective aligner hygiene is recognized as an important part of orthodontic treatments and oral hygiene. However, there is no effective cleansing method for removable aligners. METHODS: In this study, we incorporated tannic acid (TA) with cetylpyridinium chloride (CPC) to develop the TA-CPC complex. The antibacterial properties of 15.8 mg/mL TA-CPC against Escherichia coli and Staphylococcus aureus were evaluated in vitro, which were compared with 5.1 mg/mL TA, 10.7 mg/mL CPC, a commercial denture cleansing solution (YA; 15 mg/mL), and water. As for the assessment of stain-removal ability, the aligners stained by coffee were soaked in cleansing solutions, and the color changes (ΔE∗) were calculated on the basis of the CIE L∗a∗b∗ color system, and the National Bureau of Standards system was used for the clinical interpretation of the color change. Atomic force microscope examination, tensile property assessment, and wavelength dispersive x-ray fluorescence analysis were performed to investigate the material compatibility of TA-CPC, and Cell Counting Kit-8 assay and live/dead assay were used to test the cytotoxicity of TA-CPC. RESULTS: The results showed that TA-CPC had a positive zeta-potential, and cation-π interaction changed the chemical environments of the phenyl group in TA-CPC, resulting in greater inhibition zones of S. aureus and E. coli than other cleaners. The quantification of the biofilm biomass and the fluorescent intensities also reflected that the TA-CPC solution exhibited better antibacterial ability. As for the ability of stain removal, ΔE∗ value of group TA-CPC was 2.84 ± 0.55, whereas those of stained aligners immersed with deionized distilled water, TA, YA, and CPC were 10.26 ± 0.04, 9.54 ± 0.24, 5.93 ± 0.36, and 4.69 ± 0.35, respectively. The visual inspection and National Bureau of Standards ratings also showed that the color of stained aligners cleansed by TA-CPC was much lighter than those of the other groups. Meanwhile, TA-CPC had good compatibility with the aligner material and cells. CONCLUSIONS: TA-CPC is a promising strategy to inhibit the formation of biofilms and remove the stains on the aligners safely, which may disinfect the aligners to improve oral health and help keep the transparent appearances of aligners without impacting the morphology and mechanical properties.

The role of snapin in regulation of brain homeostasis.

Brain homeostasis refers to the normal working state of the brain in a certain period, which is important for overall health and normal life activities. Currently, there is a lack of effective treatment methods for the adverse consequences caused by brain homeostasis imbalance. Snapin is a protein that assists in the formation of neuronal synapses and plays a crucial role in the normal growth and development of synapses. Recently, many researchers have reported the association between snapin and neurologic and psychiatric disorders, demonstrating that snapin can improve brain homeostasis. Clinical manifestations of brain disease often involve imbalances in brain homeostasis and may lead to neurological and behavioral sequelae. This article aims to explore the role of snapin in restoring brain homeostasis after injury or diseases, highlighting its significance in maintaining brain homeostasis and treating brain diseases. Additionally, it comprehensively discusses the implications of snapin in other extracerebral diseases such as diabetes and viral infections, with the objective of determining the clinical potential of snapin in maintaining brain homeostasis.

Single-cell transcriptional profiling reveals immunomodulatory properties of stromal and epithelial cells in periodontal immune milieu with diabetes in rats.

Periodontitis is the sixth major complication of diabetes. Gingiva, as an important component of periodontal tissues, serves as the first defense barrier against infectious stimuli. However, relatively little is known about cellular heterogeneity and cell-specific changes in gingiva in response to diabetes-associated periodontitis. To characterize molecular changes linking diabetes with periodontitis, we profiled single-cell transcriptome analyses of a total of 45,259 cells from rat gingiva with periodontitis under normoglycemic and diabetic condition. The single-cell profiling revealed that stromal and epithelial cells of gingiva contained inflammation-related subclusters enriched in functions of immune cell recruitment. Compared to normoglycemic condition, diabetes led to a reduction in epithelial basal cells, fibroblasts and smooth muscle cells in gingiva with periodontitis. Analysis of differentially expressed genes indicated that stromal and epithelial populations were reprogrammed towards pro-inflammatory phenotypes promoting immune cell recruitment in diabetes-related periodontitis. In aspect of immune cells, diabetes prominently enhanced neutrophil and M1 macrophage infiltration in periodontitis lesions. Cell-cell communications revealed enhanced crosstalk between stromal/epithelial cells and immune cells mediating by chemokine/chemokine receptor interplay in diabetes-associated periodontitis. Our findings deconvolved cellular heterogeneity of rat gingiva associated with periodontitis and diabetes, uncovered altered immune milieu caused by the disease, and revealed immunomodulatory functions of stromal and epithelial cells in gingival immune niche. The present study improves the understanding of the link between the diabetes and periodontitis and helps in formulating precise therapeutic strategies for diabetes-enhanced periodontitis.

Functional connectomic profile correlates with effective anterior thalamic stimulation for refractory epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.

Conjugated Polymeric Materials in Biological Imaging and Cancer Therapy.

Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.

Silk fibroin carriers with sustained release capacity for treating neurological diseases.

Neurological diseases such as traumatic brain injury, cerebral ischemia, Parkinson's, and Alzheimer's disease usually occur in the central and peripheral nervous system and result in nervous dysfunction, such as cognitive impairment and motor dysfunction. Long-term clinical intervention is necessary for neurological diseases where neural stem cell transplantation has made substantial progress. However, many risks remain for cell therapy, such as puncture bleeding, postoperative infection, low transplantation success rate, and tumor formation. Sustained drug delivery, which aims to maintain the desired steady-state drug concentrations in plasma or local injection sites, is considered as a feasible option to help overcome side effects and improve the therapeutic efficiency of drugs on neurological diseases. Natural polymers such as silk fibroin have excellent biocompatibility, which can be prepared for various end-use material formats, such as microsphere, gel, coating/film, scaffold/conduit, microneedle, and enables the dynamic release of loaded drugs to achieve a desired therapeutic response. Sustained-release drug delivery systems are based on the mechanism of diffusion and degradation by altering the structures of silk fibroin and drugs, factors, and cells, which can induce nerve recovery and restore the function of the nervous system in a slow and persistent manner. Based on these desirable properties of silk fibroin as a carrier with sustained-release capacity, this paper discusses the role of various forms of silk fibroin-based drug delivery materials in treating neurological diseases in recent years.

Intratumor microbiota: a novel tumor component.

Bacteria have been found in tumors for over 100 years, but the irreproducibility of experiments on bacteria, the limitations of science and technology, and the contamination of the host environment have severely hampered most research into the role of bacteria in carcinogenesis and cancer treatment. With the development of molecular tools and techniques (e.g., macrogenomics, metabolomics, lipidomics, and macrotranscriptomics), the complex relationships between hosts and different microorganisms are gradually being deciphered. In the past, attention has been focused on the impact of the gut microbiota, the site where the body's microbes gather most, on tumors. However, little is known about the role of microbes from other sites, particularly the intratumor microbiota, in cancer. In recent years, an increasing number of studies have identified the presence of symbiotic microbiota within a large number of tumors, bringing the intratumor microbiota into the limelight. In this review, we aim to provide a better understanding of the role of the intratumor microbiota in cancer, to provide direction for future experimental and translational research, and to offer new approaches to the treatment of cancer and the improvement of patient prognosis.

Upregulation of RAB7 is related to neuronal pyroptosis after spinal cord injury in rats.

Rab7 belongs to the Ras small GTPase superfamily, and abnormal expression of Rab7 can cause neuropathy and lipid metabolism diseases. Studies have shown that Rab7 plays a crucial role in the inner membrane translocase. However, the role of Rab7 in the regulatory mechanisms of cell survival in spinal cord injury remains unknown. We used a rat spinal cord injury (SCI) model to explore the cellular localization and expression of Rab7 after SCI in this study. Western blot analysis showed that Rab7 was expressed in the spinal cord tissue. On the first day, it significantly increased and peaked after SCI on the third day. Furthermore, western blotting also demonstrated that pyroptosis-related protein Gasdermin D (GSDMD), Caspase-1, apoptosis-associated speck-like protein (ASC) expression peaked after the third-day post-injury. Importantly, the immunohistochemistry analysis revealed that Rab7 was completely colocalized with ASC in neurons after SCI. These results suggested that Rab7 was colocalized with NeuN and ASC, involved in the pyroptosis of neurons, and closely related to the spinal cord after injury.

Deciphering the Synergies of Reductive Soil Disinfestation Combined with Biochar and Antagonistic Microbial Inoculation in Cucumber Fusarium Wilt Suppression Through Rhizosphere Microbiota Structure.

Application of reductive soil disinfestation (RSD), biochar, and antagonistic microbes have become increasingly popular strategies in a microbiome-based approach to control soil-borne diseases. The combined effect of these remediation methods on the suppression of cucumber Fusarium wilt associated with microbiota reconstruction, however, is still unknown. In this study, we applied RSD treatment together with biochar and microbial application of Trichoderma and Bacillus spp. in Fusarium-diseased cucumbers to investigate their effects on wilt suppression, soil chemical changes, microbial abundances, and the rhizosphere communities. The results showed that initial RSD treatment followed by biochar amendment (RSD-BC) and combined applications of microbial inoculation and biochar (RSD-SQR-T37-BC) decreased nitrate concentration and raised soil pH, soil organic carbon (SOC), and ammonium in the treated soils. Under RSD, the applications of Bacillus (RSD-SQR), Trichoderma (RSD-T37), and biochar (RSD-BC) suppressed wilt incidence by 26.8%, 37.5%, and 32.5%, respectively, compared to non-RSD treatments. Moreover, RSD-SQR-T37-BC and RSD-T37 caused greater suppressiveness of Fusarium wilt and F. oxysporum by 57.0 and 33.5%, respectively. Rhizosphere beta diversity and alpha diversity revealed a difference between RSD-treated and non-RSD microbial groups. The significant increase in the abundance, richness, and diversity of bacteria, and the decrease in the abundance and diversity of fungi under RSD-induced treatments attributed to the general suppression. Identified bacterial (Bacillus, Pseudoxanthomonas, Flavobacterium, Flavisolibacter, and Arthrobacter) and fungal (Trichoderma, Chaetomium, Cladosporium, Psathyrella, and Westerdykella) genera were likely the potential antagonists of specific disease suppression for their significant increase of abundances under RSD-treated soils and high relative importance in linear models. This study infers that the RSD treatment induces potential synergies with biochar amendment and microbial applications, resulting in enhanced general-to-specific suppression mechanisms by changing the microbial community composition in the cucumber rhizosphere.

miR-20a-5p regulated SMAD6 to inhibit chondrogenesis of hDPSCs.

OBJECTIVES: Chondrogenic differentiation of human dental pulp stem cells (hDPSCs) is highly promising for cartilage repair. The specific mechanism, however, still needs to be explicated. MATERIALS AND METHODS: In this study, we isolated hDPSCs and transfected cells with lentiviruses containing an over-expression, knock-down, or negative control of miR-20a-5p. Three-D pellet cultures of hDPSCs were used for the chondrogenic induction. Following the pellet culture period, chondrogenesis was assessed by histological and immunohistochemical analysis and expression of chondrogenic-related genes. Dual-luciferase report assay was performed to determine potential targeted genes of miR-20a-5p, and the phosphorylation levels of P65 and IκBα were explored. Animal experiments were performed to determine the effect of miR-20a-5p on cartilage regeneration. RESULTS: miR-20a-5p was showed to repress the expression of SMAD6 to inhibit the chondrogenic differentiation of hDPSCs. Accordingly, the knock-down of miR-20a-5p promoted cartilage regeneration in the osteochondral defects of rats. Mechanically, it is indicated that NF-κB signaling is the potential down-stream network of miR-20a-5p/Smad6 crosstalk during chondrogenic differentiation. CONCLUSIONS: miR-20a-5p could target SMAD6 to activate NF-κB signaling pathway, and thus inhibit chondrogenesis of hDPSCs, which provided promising therapeutic target for cartilage defects clinically.

Effects of Reductive Soil Disinfestation Combined with Liquid-Readily Decomposable Compounds and Solid Plant Residues on the Bacterial Community and Functional Composition.

Reductive soil disinfestation (RSD) incorporated with sole plant residues or liquid-readily decomposable compounds is an effective management strategy to improve soil health. However, the synthetic effects of RSD incorporated with liquid-readily decomposable compounds and solid plant residues on soil ecosystem services remain unclear. Field experiments were carried out to investigate the effects of untreated soil (CK), RSD incorporated with sawdust (SA), molasses (MO), and their combinations (SA + MO) on the bacterial community and functional composition. The results showed that RSD treatments significantly altered soil bacterial community structure compared to CK treatment. The bacterial community structure and composition in MO and SA + MO treatments were clustered compared to SA treatment. This was mainly attributed to the readily decomposable carbon sources in molasses having a stronger driving force to reshape the soil microbial community during the RSD process. Furthermore, the functional compositions, such as the disinfestation efficiency of F. oxysporum (96.4 - 99.1%), abundances of nitrogen functional genes, soil metabolic activity, and functional diversity, were significantly increased in all of the RSD treatments. The highest disinfestation efficiency and abundances of denitrification (nirS and nrfA) and nitrogen fixation (nifH) genes were observed in SA + MO treatment. Specifically, SA + MO treatment enriched more abundant beneficial genera, e.g., Oxobacter, Paenibacillus, Cohnella, Rummeliibacillus, and Streptomyces, which were significantly and positively linked to disinfestation efficiency, soil metabolic activity, and denitrification processes. Our results indicated that combining RSD practices with liquid-readily decomposable compounds and solid plant residues could effectively improve soil microbial community and functional composition.

High carbon resource diversity enhances the certainty of successful plant pathogen and disease control.

The host-associated microbiome highly determines plant health. Available organic resources, such as food for microbes, are important in shaping microbial community structure and multifunctionality. However, how using organic resources precisely manipulates the soil microbiome and makes it supportive of plant health remains unclear. Here, we experimentally tested the influence of carbon resource diversity on the microbial trophic network and pathogen invasion success in a microcosm study. We further explored how resource diversity affects microbial evenness, community functions, and plant disease outcomes in systems involving tomato plants and the in vivo soil microbiome. Increasing available resource diversity altered trophic network architecture, increased microbial evenness, and thus increased the certainty of successful pathogen control. By contrast, the invasion resistance effects of low resource diversity were less effective and highly varied. Accordingly, increases in the evenness and connection of dominant species induced by high resource diversity significantly contributed to plant disease suppression. Furthermore, high carbohydrate diversity upregulated plant immune system regulation-related microbial functions. Our results deepen the biodiversity-invasion resistance theory and provide practical guidance for the control of plant pathogens and diseases by using organic resource-mediated approaches, such as crop rotation, intercropping, and organic amendments.

Down-regulation of hsa-circ-0107593 promotes osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

OBJECTIVES: Increasing evidence indicated circRNAs were involved in stem cells osteogenesis differentiation. Herein, we aimed to clarify the role of hsa-circ-0107593 during the osteogenesis process of human adipose-derived stem cells (hADSCs) and the underlying mechanisms. METHODS: The ring structure of hsa-circ-0107593 was confirmed using RNase R treatment and Sanger sequencing. Nucleoplasmic separation and fluorescence in situ hybridization detected hsa-circ-0107593 distribution. Lentivirus and siRNA were used to modulate the expression of hsa-circ-0107593, and the binding relationship between hsa-circ-0107593 and miR-20a-5p was verified by luciferase assay and RNA immunoprecipitation. We detected the osteogenic activity of hADSCs through alkaline phosphatase staining, alizarin red S staining, real-time polymerase chain reaction (RT-PCR), western blot, and cellular immunofluorescence experiment. In vivo, micro-computed tomography was performed to analyze bone formation around skull defect. RESULTS: RT-PCR results exhibited that hsa-circ-0107593 was downregulated while miR-20a-5p was upregulated during hADSCs osteogenesis. In vivo and in vitro experiments results indicated that knocking down hsa-circ-0107593 promoted the osteogenic differentiation of hADSCs, while overexpression of hsa-circ-0107593 showed an inhibitory effect on hADSCs osteogenic differentiation. In vitro experiment results showed hsa-circ-0107593 acted as a hADSCs osteogenic differentiation negative factor for it inhibited the suppressing effect of miR-20a-5p on SMAD6. CONCLUSION: Knocking down hsa-circ-0107593 acts as a positive factor of the osteogenic differentiation of hADSCs via miR-20a-5p/SMAD6 signaling.

miR-17-92 cluster in osteoarthritis: Regulatory roles and clinical utility.

Osteoarthritis (OA) is the most prevalent articular disease, especially in aged population. Caused by multi-factors (e.g., trauma, inflammation, and overloading), OA leads to pain and disability in affected joints, which decreases patients' quality of life and increases social burden. In pathophysiology, OA is mainly characterized by cartilage hypertrophy or defect, subchondral bone sclerosis, and synovitis. The homeostasis of cell-cell communication is disturbed as well in such pro-inflammatory microenvironment, which provides clues for the diagnosis and treatment of OA. MicoRNAs (miRNAs) are endogenous non-coding RNAs that regulate various processes via post-transcriptional mechanisms. The miR-17-92 cluster is an miRNA polycistron encoded by the host gene called MIR17HG. Mature miRNAs generated from MIR17HG participate in biological activities such as oncogenesis, neurogenesis, and modulation of the immune system. Accumulating evidence also indicates that the expression level of miRNAs in the miR-17-92 cluster is tightly related to the pathological processes of OA, such as chondrocyte apoptosis, extracellular matrix degradation, bone remodeling, and synovitis. In this review, we aim to summarize the roles of the miR-17-92 cluster in the underlying molecular mechanism during the development and progression of OA and shed light on the new avenue of the diagnosis and treatment of OA.