MLL-AF9 regulates transcriptional initiation in mixed lineage leukemic cells.

MLL-fusion proteins (MLL-FPs) are believed to maintain gene activation and induce mixed lineage leukemia (MLL) through aberrantly stimulating transcriptional elongation, but the underlying mechanisms are incompletely understood. Here we show that both MLL1 and AF9, one of the major fusion partners of MLL1, mainly occupy promoters and distal intergenic regions, exhibiting chromatin occupancy patterns resembling that of RNA polymerase II (Pol II) in HEL, a human cell line without MLL1 arrangement (MLLr). MLL1 and AF9 only co-regulate over a dozen genes despite of their co-occupancy on thousands of genes. They do not interact with each other, and their chromatin occupancy is also independent of each other. Moreover, AF9 deficiency in HEL cells decreases global TBP occupancy while decreases CDK9 occupancy on a small number of genes, suggesting an accessory role of AF9 in CDK9 recruitment and a possible major role in transcriptional initiation via initiation factor recruitment. Importantly, MLL1 and MLL-AF9 occupy promoters and distal intergenic regions, exhibiting identical chromatin occupancy patterns in MLL cells, and MLL-AF9 deficiency decreased occupancy of TBP and TFIIE on major target genes of MLL-AF9 in iMA9, a murine acute myeloid leukemia (AML) cell line inducibly expressing MLL-AF9, suggesting that it can also regulate initiation. These results suggest that there is no difference between MLL1 and MLL-AF9 with respect to location and size of occupancy sites, contrary to what people have believed, and that MLL-AF9 may also regulate transcriptional initiation in addition to widely-believed elongation.

Quercetin through miR-147-5p/Clip3 axis reducing Th17 cell differentiation to alleviate periodontitis.

Background: Quercetin (QU) plays an important role in treating periodontitis; however, the mechanism through which microRNAs regulate Th17 cell differentiation has not been determined. Methods: QU was administered intragastrically to periodontitis rats once a day for one month. The morphology of alveolar bone was observed by micro-CT, gingival tissue structure was observed by HE staining, IL-6, TNF-α, IL-17A, RORγt, FOXP3 and IL-10 were detected by immunohistochemical staining, and Th17 and Treg cells in the peripheral blood were detected by flow cytometry. CD4+T cells were induced to differentiate into Th17 cells in vitro. Cell viability was determined by CCK8, and IL-17A and RORγt were detected by qPCR. Th17 cells were detected by flow cytometry, microRNA sequencing and bioinformatics analysis were used to screen key microRNAs, the phenotypic changes of Th17 cells were observed after overexpressed microRNAs via mimics. TargetScan database, in situ hybridization, and dual-luciferase reporter experiment were used to predict and prove target genes of microRNAs. The phenotype of Th17 cells was observed after overexpression of microRNA and target gene. Results: Compared with periodontitis group, the distance from cementoenamel junction(CEJ) to alveolar bone(AB) was decreased, the structure of gingival papilla was improved, IL-6, TNF-α, IL-17, and RORγt were downregulated, FOXP3 and IL-10 were upregulated, the proportion of Th17 decreased and Treg increased in peripheral blood after QU treatment. Compared with Th17 cell group, mRNA levels of IL-17A and RORγt were decreased, and proportion of Th17 cells was significantly lower in the coculture group. MiR-147-5p was low in control group, upregulated in Th17 cell group, and downregulated after QU intervention, it's eight bases were inversely related to 3'UTR of Clip3, miR-147-5p with Clip3 were co-located in cells of periodontal tissue. Compared with those in Th17-mimicsNC + QU cells, the mRNA levels of RORγt and IL-17A upregulated, and proportion of Th17 cells increased in Th17-miR-147-5p + QU cells. The miR-147-5p mimics inhibited the luciferase activity of the WT Clip3 3'UTR but had no effect on the Mut Clip3 3'UTR. Clip3 was significantly downregulated after the overexpression of miR-147-5p. Mimics transfected with miR-147-5p reversed the decrease in the proportion of Th17 cells induced by QU, while the overexpression of Clip3 antagonized the effect of miR-147-5p and further reduced the proportion of Th17 cells. Moreover, the overexpression of miR-147-5p reversed the decreases in the mRNA levels of IL-17 and RORγt induced by QU treatment, while pcDNA3.1 Clip3 treatment further decreased the mRNA levels of IL-17 and RORγt. Conclusion: QU reducing inflammatory response and promoting alveolar bone injury and repair, which closely relative to inhibit the differentiation of CD4+T cells into Th17 cells by downregulating miR-147-5p to promote the activation of Clip3.

Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is a crucial public health problem, accounting for approximately 2% of all cancers globally and 90% of oral malignancies over the world. Unfortunately, despite the achievements in surgery, radiotherapy, and chemotherapy techniques over the past decades, OSCC patients still low 5-year survival rate. Cisplatin, a platinum-containing drug, serves as one of the first-line chemotherapeutic agents of OSCC. However, the resistance to cisplatin significantly limits the clinical practice and is a crucial factor in tumor recurrence and metastasis after conventional treatments. Ferroptosis is an iron-based form of cell death, which is initiated by the intracellular accumulation of lipid peroxidation and reactive oxygen species (ROS). Interestingly, cisplatin-resistant OSCC cells exhibit lower level of ROS and lipid peroxidation compared to sensitive cells. The reduced ferroptosis in cisplatin resistance cells indicates the potential relationship between cisplatin resistance and ferroptosis, which is proved by recent studies showing that in colorectal cancer cells. However, the modulation pathway of ferroptosis reversing cisplatin resistance in OSCC cells still remains unclear. This article aims to concisely summarize the molecular mechanisms and evaluate the relationship between ferroptosis and cisplatin resistance OSCC cells, thereby providing novel strategies for overcoming cisplatin resistance and developing new therapeutic approaches.

Yunnan Baiyao Might Mitigate Periodontitis Bone Destruction by Inhibiting Autophagy and Promoting Osteoblast Differentiation in vivo, ex vivo and in vitro.

Background and Objective: Periodontitis is an inflammatory disease that eventually destroys tooth-supporting tissue. Yunnan Baiyao (YNBY), a traditional Chinese medicine compound with haemostatic and anti-inflammatory properties has shown therapeutic potential in several diseases. Our previous study revealed that YNBY suppressed osteoclast differentiation in periodontitis. The purpose of this study is to investigate the influences of YNBY on osteoblasts and explore its potential mechanisms. Materials and Methods: A rat periodontitis model was established by ligation of maxillary second molars. After the end of modelling, histopathological observation by hematoxylin-eosin (HE) staining and Masson trichrome staining, detection of bone resorption by Micro-CT scanning, detection of osteoclasts by tartrate-resistant acid phosphatase (TRAP) staining, expression of osteocalcin (OCN) and microtubule-associated protein 1 light chain 3 (LC3) by immunohistochemistry. Lipopolysaccharides was used to irritate MC3T3-E1 osteoblastic cells and ex vivo calvarial organ as an in vitro model of inflammation. CCK-8 assay was performed to examine the toxicity of YNBY to MC3T3-E1 osteoblastic cells. Osteogenesis was assessed with alizarin red staining, immunofluorescence staining, Western blot and immunohistochemical staining. Transmission electron microscopy, fluorescent double staining, Western blot and immunohistochemical staining were employed to detect autophagy. Results: Histological and micro-CT analyses revealed that YNBY gavage reduced bone loss caused by experimental periodontitis and upregulated osteogenic proteins in vivo. YNBY attenuated the production of autophagy-related proteins in periodontitis rats. Additionally, YNBY promoted osteogenesis by inhibiting inflammation-induced autophagy in vitro. Furthermore, YNBY suppressed LPS-mediated bone resorption and promoted the production of osteoblast-related proteins in inflamed calvarial tissues ex vivo. Conclusion: This study demonstrated, through in vivo, in vitro and ex vivo experiments, that YNBY promoted osteoblast differentiation by suppressing autophagy, which markedly alleviated bone destruction caused by periodontitis.

Bacterial isolation and genome analysis of a novel Klebsiella quasipneumoniae phage in southwest China's karst area.

BACKGROUND: Southwest China is one of the largest karst regions in the world. Karst environment is relatively fragile and vulnerable to human activities. Due to the discharge of sewage and domestic garbage, the karst system may be polluted by pathogenic bacteria. The detection of bacterial distribution and identification of phage capable of infecting them is an important approach for environmental assessment and resource acquisition. METHODS: Bacteria and phages were isolated from karst water in southwest China using the plate scribing and double plate method, respectively. Isolated phage was defined by transmission electron microscopy, one-step growth curve and optimal multiplicity of infection (MOI). Genomic sequencing, phylogenetic analysis, comparative genomic and proteomic analysis were performed. RESULTS: A Klebsiella quasipneumoniae phage was isolated from 32 isolates and named KL01. KL01 is morphologically identified as Caudoviricetes with an optimal MOI of 0.1, an incubation period of 10 min, and a lysis period of 60 min. The genome length of KL01 is about 45 kb, the GC content is 42.5%, and it contains 59 open reading frames. The highest average nucleotide similarity between KL01 and a known Klebsiella phage 6939 was 83.04%. CONCLUSIONS: KL01 is a novel phage, belonging to the Autophagoviridae, which has strong lytic ability. This study indicates that there were not only some potential potentially pathogenic bacteria in the karst environment, but also phage resources for exploration and application.

Few-Shot Face Stylization via GAN Prior Distillation.

Face stylization has made notable progress in recent years. However, when training on limited data, the performance of existing approaches significantly declines. Although some studies have attempted to tackle this problem, they either failed to achieve the few-shot setting (less than 10) or can only get suboptimal results. In this article, we propose GAN Prior Distillation (GPD) to enable effective few-shot face stylization. GPD contains two models: a teacher network with GAN Prior and a student network that fulfills end-to-end translation. Specifically, we adapt the teacher network trained on large-scale data in the source domain to the target domain using a handful of samples, where it can learn the target domain's knowledge. Then, we can achieve few-shot augmentation by generating source domain and target domain images simultaneously with the same latent codes. We propose an anchor-based knowledge distillation module that can fully use the difference between the training and the augmented data to distill the knowledge of the teacher network into the student network. The trained student network achieves excellent generalization performance with the absorption of additional knowledge. Qualitative and quantitative experiments demonstrate that our method achieves superior results than state-of-the-art approaches in a few-shot setting.

Targeted exosome-based nanoplatform for new-generation therapeutic strategies.

Exosomes, typically 30-150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g. proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.

Emerging strategies for nerve repair and regeneration in ischemic stroke: neural stem cell therapy.

Ischemic stroke is a major cause of mortality and disability worldwide, with limited treatment options available in clinical practice. The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function. Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect. Neural stem cells regulate multiple physiological responses, including nerve repair, endogenous regeneration, immune function, and blood-brain barrier permeability, through the secretion of bioactive substances, including extracellular vesicles/exosomes. However, due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation, limitations in the treatment effect remain unresolved. In this paper, we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke, review current neural stem cell therapeutic strategies and clinical trial results, and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells. We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.

Yunnan Baiyao Inhibits Periodontitis by Suppressing the Autophagic Flux.

BACKGROUND: Yunnan Baiyao (YNBY), a traditional Chinese medicine, is renowned for its anti-inflammatory properties. Recent studies have suggested that YNBY plays a significant role in inhibiting osteoclast differentiation and autophagy, which are essential processes in inflammation and bone resorption associated with periodontitis. However, the precise relationship between autophagy and the mechanism by which YNBY inhibits osteoclastogenesis remains unexplored.The primary objective of this study was to investigate the inhibitory effects of YNBY on the process of osteoclastogenesis and its potential in preventing inflammatory bone loss. METHODS: The animals were subjected to sacrifice at intervals of 2, 4, and 6 weeks postintervention whilst under deep anaesthesia, and specimens were subsequently collected. The specimens were subjected to hematoxylin and eosin (HE) staining, in addition to tartrate-resistant acid phosphatase (TRAP) staining and subsequently imaged employing a digital scanner. The confirmation of osteoclast (OC) differentiation and autophagic flux was achieved through various techniques, including western blotting, transmission electron microscopy (TEM), TRAP staining, pit formation assay, and immunofluorescence. RESULTS: The microcomputed tomography images provided evidence of the effective inhibition of alveolar bone absorption at 2, 4, and 6 weeks following YNBY treatment. Additionally, the histomorphometric evaluations of tissue segments stained with HE and TRAP, which involved measuring the distance between the alveolar bone crest (ABC) and cementoenamel junction (CEJ) and quantifying TRAP-positive OCs, yielded comparable results to those obtained through computed tomography analysis. YNBY treatment resulted in a decrease in the CEJ-ABC distance and inhibition of OC differentiation. Furthermore, in vitro studies showed that the autophagy modulators rapamycin (RAP) and 3-methyladenine (3-MA) significantly affected OC differentiation and function. YNBY attenuated the impact of RAP on the differentiation of OCs, autophagy-related factor activation, and bone resorption. CONCLUSIONS: We hypothesise that YNBY suppresses the differentiation of OC and bone resorption by blocking autophagy. This study reveals that targeting autophagy might be a new alternative treatment methodology for periodontitis treatment.

Induction of Lumbar Disc Degeneration in Rabbits Through a Transabdominal Approach.

Lower back pain is an extremely common medical issue in populations worldwide. One of the main contributors to lower back pain is intervertebral disc (IVD) degeneration. An ideal animal model of IVD degeneration is essential to study the pathophysiology of lower back pain and investigate potential therapeutic strategies. Rabbit models are reliable, economical, and easily established animal models. The retroperitoneal approach has been widely used to induce IVD degeneration in rabbit models. However, there are reported complications associated with this technique, such as the avulsion of segmental arteries and nerve root injury. In this paper, we aim to show a surgical protocol using needle puncture to establish rabbit lumbar disc degeneration via a transabdominal approach. Consequently, radiological checks and histological analyses indicated that lumbar disc degeneration was successfully established in rabbits. This surgical protocol presents the precise location of target discs and high reproducibility of IVD degeneration models with fewer complications.

Effect of thyroid hormone replacement treatment on cardiac diastolic function in adult patients with subclinical hypothyroidism: a meta-analysis.

Background: Although subclinical hypothyroidism (SCH) is related to abnormalities in left ventricular diastolic function, the use of levothyroxine as a regular treatment remains debatable. This meta-analysis aimed to determine whether thyroid hormone replacement therapy affects cardiac diastolic function in patients with SCH as measured by echocardiography. Methods: This meta-analysis included a search of the EMBASE, PubMed, Web of Science, and Cochrane Library databases from their inception to May 18, 2023, for studies analyzing cardiac morphology and functional changes in patients with SCH before and after thyroid hormone replacement. The outcome measures were cardiac morphology and diastolic and overall cardiac function, as assessed using ultrasound parameters (including ventricular wall thickness, chamber size, mitral wave flow, tissue Doppler, and speckle tracking). The quality of the studies was assessed using the Newcastle-Ottawa Scale. The standard mean differences (MDs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Results: Seventeen studies met the inclusion criteria. A total of 568 patients participated and completed the follow-up. All studies specifically stated that serum thyrotropin levels returned to normal by the end of the study period. Compared with baseline levels, no significant morphological changes were observed in the heart. In terms of diastolic function, we discovered that the ratios of E-velocity to A-velocity (E/A) had greatly improved after thyroid hormone replacement therapy, whereas the ratios of the mitral inflow E wave to the tissue Doppler e' wave (E/e') had not. Global longitudinal strain (GLS) increased significantly after treatment with levothyroxine. Conclusion: In adult patients with SCH, thyroid hormone supplementation can partially but not completely improve parameters of diastolic function during the observation period. This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement, an updated guideline for reporting systematic reviews (11) and was registered with INPLASY (INPLASY202320083). Systematic review registration: https://inplasy.com/inplasy-2023-2-0083.

Remote ischemic conditioning attenuates oxidative stress and inflammation via the Nrf2/HO-1 pathway in MCAO mice.

The protective effects of remote ischemic conditioning (RIC) on acute ischemic stroke have been reported. However, the protective mechanisms of RIC have not been fully elucidated. This study aimed to investigate whether RIC could reduce oxidative stress and inflammatory responses in middle cerebral artery occlusion (MCAO)-reperfusion mice via the nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. C57BL/6 mice were subjected to MCAO and underwent RIC twice daily at 1, 3, and 7 days after MCAO. ML385 was used to specifically inhibit Nrf2 in MCAO mice. Neurological deficit scores, infarct volume, and hematoxylin-eosin (HE) staining were assessed. Oxidative stress levels were assessed based on total antioxidant capacity (TAC), malonaldehyde (MDA), superoxide dismutase (SOD), and glutathione/glutathione disulfide (GSH/GSSG). mRNA levels were detected using real-time polymerase chain reaction (PCR), and protein levels were detected using western blotting and enzyme-linked immunosorbent assay (ELISA). Protein localization was investigated using immunofluorescence staining. RIC significantly reduced infarct volume and improved neurological function and histological changes after MCAO. RIC significantly increased TAC, SOD, and GSH/GSSG levels and decreased MDA levels. RIC significantly increased Nrf2 and HO-1 mRNA levels and decreased Keap1, NLRP3, and Cleaved Caspase-1 mRNA levels. RIC significantly increased Nrf2, HO-1, and NQO1 protein expression and decreased Keap1, NLRP3, Cleaved Caspase-1, Cleaved IL-1ß, IL-6, and TNF-α protein expression. RIC promoted the activation and translocation of Nrf2 into the nucleus. The protective effects of RIC were abolished by ML385 treatment. In conclusion, our findings suggest that RIC alleviates oxidative stress and inflammatory responses via the Nrf2/HO-1 pathway, which in turn improves neurobehavioral function. RIC may provide novel therapeutic options for acute ischemic stroke.

Tox4 regulates transcriptional elongation and reinitiation during murine T cell development.

HMG protein Tox4 is a regulator of PP1 phosphatases with unknown function in development. Here we show that Tox4 conditional knockout in mice reduces thymic cellularity, partially blocks T cell development, and decreases ratio of CD8 to CD4 through decreasing proliferation and increasing apoptosis of CD8 cells. In addition, single-cell RNA-seq discovered that Tox4 loss also impairs proliferation of the fast-proliferating double positive (DP) blast population within DP cells in part due to downregulation of genes critical for proliferation, notably Cdk1. Moreover, genes with high and low expression level are more dependent on Tox4 than genes with medium expression level. Mechanistically, Tox4 may facilitate transcriptional reinitiation and restrict elongation in a dephosphorylation-dependent manner, a mechanism that is conserved between mouse and human. These results provide insights into the role of TOX4 in development and establish it as an evolutionarily conserved regulator of transcriptional elongation and reinitiation.

Face Database Protection via Beautification with Chaotic Systems.

The database of faces containing sensitive information is at risk of being targeted by unauthorized automatic recognition systems, which is a significant concern for privacy. Although there are existing methods that aim to conceal identifiable information by adding adversarial perturbations to faces, they suffer from noticeable distortions that significantly compromise visual perception, and therefore, offer limited protection to privacy. Furthermore, the increasing prevalence of appearance anxiety on social media has led to users preferring to beautify their faces before uploading images. In this paper, we design a novel face database protection scheme via beautification with chaotic systems. Specifically, we construct the adversarial face with better visual perception via beautification for each face in the database. In the training, the face matcher and the beautification discriminator are federated against the generator, prompting it to generate beauty-like perturbations on the face to confuse the face matcher. Namely, the pixel changes produced by face beautification mask the adversarial perturbations. Moreover, we use chaotic systems to disrupt the order of adversarial faces in the database, further mitigating the risk of privacy leakage. Our scheme has been extensively evaluated through experiments, which show that it effectively defends against unauthorized attacks while also yielding good visual results.

Transfer route and driving forces of antibiotic resistance genes from reclaimed water to groundwater.

The infiltration of reclaimed water has created a significant environmental risk due to the spread of antibiotic resistance genes (ARGs) in riparian groundwater. Reclaimed water from wastewater treatment plants (WWTPs) had been identified as a source of both antibiotics and ARGs in groundwater, based on their spatial and temporal distribution. The assembly process of microbial communities in the groundwater of the infiltration zone was more influenced by deterministic processes. Co-occurrence network analysis revealed that Thermotoga, Desulfotomaculum, Methanobacterium, and other such genera were dominant shared genera. These were considered core genera and hosts of ARGs for transport from reclaimed water to groundwater. The most abundant ARG in these shared genera was MacB, enriched in groundwater point G3 and potentially transferred from reclaimed water to groundwater by Acidovorax, Hydrogenophaga, Methylotenera, Dechloromonas, and Nitrospira. During the infiltration process, environmental factors and the tradeoff between energy metabolism and antibiotic defense strategy may have affected ARG transfer. Understanding the transfer route and driving forces of ARGs from reclaimed water to groundwater provided a new perspective for evaluating the spread risk of ARGs in reclaimed water infiltration.

Application of Stand-Alone Oblique Lateral Interbody Fusion in L4-5 Lumbar Diseases.

Lumbar spine diseases often cause lower back pain, lower extremity pain, numbness, and paresthesia. In severe cases, intermittent claudication may occur, affecting the quality of life of patients. Surgery is often required when conservative treatment fails, or when patients' symptoms become unbearable. Surgical treatments include laminectomy and discectomy, as well as interbody fusion. The main purpose of laminectomy and discectomy is to relieve nerve compression; however, recurrence is common due to spinal instability. Interbody fusion improves stability while relieving nerve compression and significantly reduces the risk of recurrence compared to non-fusion surgery. Nonetheless, conventionally posterior intervertebral fusion requires separation of the muscles to expose the operated segment, which causes more trauma to the patient. In contrast, the oblique lateral interbody fusion (OLIF) technique achieves spinal fusion with minimal trauma to the patients and shortens the recovery time. This article introduces procedures of stand-alone OLIF surgery performed in the lumbar spine, providing a reference for other spine surgeons.

Association between anemia and lumbar disc degeneration in patients with low back pain: an observational retrospective study.

OBJECTIVE: The goal of this study was to evaluate the possible associations between anemia and morphologic features of lumbar disc degeneration (LDD) in subjects with low back pain. MATERIALS AND METHODS: A total of 131 patients with normocytic or microcytic anemia (mean age 41.0 ± 6.4 yrs, BMI: 24.8 ± 3.3 kg/m2, 12.2% men) and a matched control group of 131 patients without anemia (mean age 41.0 ± 6.4 yrs, BMI: 24.9 ± 3.1 kg/m2, 12.2% men) were evaluated for LDD according to the Pfirrmann scoring system. The primary outcome was the difference of radiological features of LDD between two groups. The second outcome was the correlation between the hemoglobin (Hb) value and disc degeneration (DD). Statistical associations were assessed by Student's t-test, Chi-square test, and Spearman correlation. RESULTS: Anemic patients had a significantly higher number of degenerated discs than non-anemic patients in the level of L2/3 and L3/4 (p < 0.05). We also found that the severe DD occurred more frequently in the level of L2/3, L3/4 and L5/S1 among anemic patients (p < 0.05). In addition, we noticed that the incidence of multilevel LDD happened much more frequently in patients with anemia (p < 0.05). The Hb value showed a borderline negative correlation with the total score of DD (p = 0.056). CONCLUSION: The results suggested that patients with anemia, and those without are radiologically different with varying patterns of DD. Patients with back pain and anemia were more likely to have extensive and severe DD. Although relevant mechanisms are not yet well understood, this study improved our understandings of the pathophysiology for LDD.

Role of lipocalin 2 in stroke.

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear. Here, a rodent model of thromboembolic stroke followed by rtPA thrombolysis at different time points was performed with or without RIC. Brain infarction, neurological outcomes, BBB permeability, and intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in the brain tissue, PDGF-CC levels in the skeletal muscle and peripheral blood were also measured. Furthermore, impact of RIC on serum PDGF-CC levels were measured in healthy subjects and AIS patients. Our results showed that RIC substantially reduced BBB injury, intracerebral hemorrhage, cerebral infarction, and neurological deficits after stroke, even when rtPA was administrated in a delayed therapeutic time window. Mechanistically, RIC significantly decreased PDGFRα activation in ischemic brain tissue and reduced blood PDGF-CC levels, which partially resulted from PDGF-CC reduction in the skeletal muscle of RIC-applied hindlimbs and platelets. Intravenous or intraventricular recombinant PDGF-CC supplementation abolished RIC protective effects on BBB integrity. Moreover, similar changes of PDGF-CC in serum by RIC were also observed in healthy humans and acute ischemic stroke patients. Together, our study demonstrates that RIC can attenuate rtPA-aggravated BBB disruption after ischemic stroke via reducing the PDGF-CC/PDGFRα pathway and thus supports RIC as a potential approach for BBB disruption prevention or treatment following thrombolysis.

Mixed organic and inorganic amendments enhance soil microbial interactions and environmental stress resistance of Tibetan barley on plateau farmland.

Sufficient crop yield while maintaining soil health and sustainable agricultural development is a global objective, serving a special challenge to certain climate-sensitive plateau areas. Despite conducting trails on a variety of soil amendments in plateau areas, systematic research is lacking regarding the influences of organic and inorganic amendments on soil quality, particularly soil microbiome. To our knowledge, this was the first study that compared the effects of inorganic, organic, and mixed amendments on typical plateau crop hulless barley (Hordeum vulgare L. var. Nudum, also known as "Qingke" in Chinese) over the course of tillering, jointing, and ripening. Microbial communities and their responses to amendments, soil properties and Tibetan hulless barley growth, yield were investigated. Results indicated that mixed organic and inorganic amendments promoted the abundance of rhizosphere microorganisms, enhancing the rhizosphere root-microbes interactions and resistance to pathogenic bacteria and environmental stresses. The rhizosphere abundant and significantly different genera Arthrobacter, Rhodanobacter, Sphingomona, Nocardioides and so on demonstrated their unique adaptation to the plateau environment based on the results of metagenomic binning. The abundance of 23 genes about plant growth and environmental adaptations in the mixed amendment soil were significantly higher than other treatments. Findings from this study suggest that the mixed organic/inorganic amendments can help establish a healthy microbiome and increase soil quality while achieving sufficient hulless barley yields in Tibet and presumably other similar geographic areas of high altitude.