Search

Abstract Psoriasis is a chronic skin disease characterized by abnormal proliferation and inflammation of epidermal keratinocytes. Fibroblast growth factor 12 (FGF12) is implicated in the regulation of diverse cellular signals; however, its precise mechanism in psoriasis requires further investigation. In this study, high expression of FGF12 is observed in the epidermis of skin lesion in psoriasis patients and imiquimod (IMQ)‐induced psoriasis like‐dermatitis. Moreover, specific loss of FGF12 in keratinocytes in IMQ‐induced psoriasis model alleviates psoriasis‐like symptoms and reduces proliferation. In vitro RNA sequencing demonstrates that knockdown of FGF12 effectively arrests the cell cycle, inhibits cell proliferation, and predominantly regulates the p53 signaling pathway. Mechanistically, FGF12 is selectively bound to the RING domain of MDM2, thus partially inhibiting the binding of β‐Trcp to MDM2. This interaction inhibits β‐Trcp‐induced‐K48 ubiquitination degradation of MDM2, thereby suppressing the activity of the p53 signaling pathway, which results in excessive cell proliferation. Last, the alleviatory effect of FGF12 deficiency on psoriasis progression is reversed by p53 knockdown. In summary, these findings provide valuable insights into the mechanisms by which FGF12 suppresses p53 signaling in keratinocytes, exacerbating the development of psoriasis. This positive regulatory loop highlights the potential of FGF12 as a therapeutic target to manage psoriasis.

In this study, we green synthesized silver nanoparticles (Ag Nps) from Hybanthus enneaspermus leaves (HE-Ag NPs) and evaluated their antimicrobial and wound-healing properties. The synthesized HE-Ag NPs were characterized using various techniques, revealing face-centered polygonal structures, a well-dispersed appearance, and an average particle size of 42–51 nm. The antimicrobial effects of HE-Ag NPs and their embedded cotton fabrics were tested against several pathogens, showing effective inhibition of growth. The cytotoxicity and anti-inflammatory properties of HE-Ag NPs were assessed using MTT assays on L929 and RAW 264.7 cells and by measuring inflammatory cytokine levels in LPS-treated RAW 264.7 cells. HE-Ag NPs did not affect the viability of L929 and RAW 264.7 cells and significantly reduced inflammatory cytokine levels. In vivo studies using an excision wound model demonstrated that HE-Ag NPs-loaded ointment significantly increased hydroxyproline, total protein, and antioxidant levels and enhanced the wound contraction rate. These findings suggest that HE-Ag NPs have potent antimicrobial properties and promote wound healing, indicating their potential for use in topical ointments for wound care.

Hydrogels exhibit exceptional suitability as wound dressing due to their remarkable three-dimensional (3D) characteristics. Here, we have reported the fabrication of hydrogels from biopolymers carboxymethyl cellulose (CMC), polyvinyl alcohol (PVA), and gelatin via a simple blending method to mimic the natural extracellular matrix. Scanning electron microscopy (SEM), water contact meters (WCM), and Fourier-transform infrared spectroscopy (FTIR) were used to evaluate the chemical structural, morphological, and wettability behavior. The wetting and degradation behavior were also found to be different for different formulations (Min. (51.60o) and Max. (113.60o)) and (Min. (38.82 mg) and Max. (3.72 mg)), respectively. Swelling was investigated in different media, including phosphate buffer saline solution (PBS) and aqueous media. It was observed that the hydrogel displayed the highest degree of swelling in an aqueous medium (Min. (597.32–1121.49 %) and Max. (1089.51–2139.73 %)) compared to PBS media (Min. (567.01–1021.85 %) and Max. (899.13–1639.17 %)). The release of Neomycin was studied in a PBS medium via the Franz diffusion method at 37 °C. The maximal release in various media demonstrated pH-responsive behavior. The viability and proliferation of fibroblast (3T3) cell lines were examined in vitro to evaluate cytocompatibility. Human Embryonic Kidney (HEK) 293 cells were used to evaluate the hydrogels' ability to promote vascularization and angiogenesis. Therefore, the data demonstrate that hydrogels that have been manufactured have qualities that make them promising for use as wound dressings in wound healing applications.

Background: Endometriosis, characterized by extrauterine endometrial tissue, leads to irregular bleeding and pelvic pain. Menstrual retrograde theory suggests fragments traverse fallopian tubes, causing inflammation and scar tissue. Prevalent among infertile women, risk factors include fewer pregnancies, delayed childbirth, irregular cycles, and familial predisposition. Treatments, medication, and surgery entail side effects. Studies link gut microbiota alterations to endometriosis, necessitating research to establish causation. We used Mendelian randomization to investigate the potential link between endometriosis and gut microbiota through genetic variants.Methods: Two-sample Mendelian randomization analyzed gut microbiota’s potential causal effects on endometriosis. Instrumental variables, robustly associated with exposures, leveraged GWAS data from MiBioGen for gut microbiota and FinnGen R8 release for endometriosis. SNPs strongly associated with exposures were instrumental variables. Rigorous assessments ensured SNP impact scrutiny on endometriosis.Results: At the genus level, Anaerotruncus, Desulfovibrio, Haemophilus, and Holdemania showed causal association with endometriosis. Specific gut microbiota exhibited causal effects on different endometriosis stages. Holdemania and Ruminococcaceae UCG002 exerted reversible, stage-specific impacts.Conclusion: Mendelian randomization provides evidence for the causal link between specific gut microbiotas and endometriosis, emphasizing the pivotal role of gut microbiota dysbiosis. Modulating gut microbiota emerges as a promising strategy for preventing and treating endometriosis.

Many naturally occurring chemical metabolites with significant cytotoxic activities have been isolated from medicinal plants and have become the leading hotspot of anti-cancer research in recent years. Hyptis rhomboidea Mart. et Gal is used as a folk medicine in South China to treat or assist in the treatment of liver disease, ulcers, and edema. But its chemical constituents have not been fully investigated yet. This study aimed to assess the cytotoxicity of H. rhomboidea, which was chemically characterized by chromatography–mass spectrometry methods. The results showed that the 95% ethanol extract of H. rhomboidea has marked inhibitory effects on five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480), with IC50 values ranging from 15.8 to 40.0 μg/mL. A total of 64 compounds were identified by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and gas chromatograph–mass spectroscopy (GC-MS) analysis of H. rhomboidea crude extract. Among them, kaempferol, quercetin, rosmarinic acid, squalene, and campesterol were found to be abundant and might be the major metabolites involved to its bioactivity. The cytotoxic characterization and metabolite profiling of H. rhomboidea displayed in this research provides scientific evidence to support its use as medicinal properties.

BackgroundThymus mandschuricus is an aromatic and medicinal plant with notable antibacterial and antioxidant properties. However, traditional breeding methods rely on phenotypic selection due to a lack of molecular resources. A high-quality reference genome is crucial for marker-assisted breeding, genome editing, and molecular genetics.ResultsWe utilized PacBio and Hi-C technologies to generate a high-quality chromosome-level reference genome for T. mandschuricus, with a size of 587.05 Mb and an N50 contig size of 8.41 Mb. The assembled genome contained 29,343 predicted protein-coding genes, and evidence of two distinct whole-genome duplications in T. mandschuricus was discovered. Comparative genomic analysis revealed rapid evolution of genes involved in phenylpropanoid biosynthesis and the CYP450 gene family in T. mandschuricus. Additionally, we reconstructed the gene families of terpenoid biosynthesis structural genes, such as TPS, BAHD, and CYP, and identified regulatory networks controlling the expression of aroma-synthesis genes by integrating transcriptome data from various organs and developmental stages. We discovered that hormones and transcription factors may collaborate in controlling aroma-synthesis gene expression.ConclusionThis study provides the first high-quality genome sequence and gene annotation for T. mandschuricus, an indigenous thyme species unique to China. The genome assembly and the comprehension of the genetic basis of fragrance synthesis acquired from this research could potentially serve as targets for future breeding programs and functional studies.

ObjectivesThe study aims to analyze factors that affect the postoperative health-related quality of life (HRQOL) of degenerative lumbar scoliosis (DLS) patients and explore the appropriate pelvic incidence minus lumbar lordosis (PI-LL) value for Chinese DLS patients.MethodsDLS patients who met the inclusion and exclusion criteria were included in this study. General information, spino-pelvic parameters, and HRQOL were collected. Correlation analysis was used to explore the spino-pelvic parameters that affect the postoperative HRQOL. Thresholds of each parameter were obtained using the receiver operating characteristic (ROC) curve. Regardless of the effect of age, DLS patients were classified into three groups according to the SRS-Schwab classification: group 0 means PI-LL 20°. Postoperative HRQOL was analyzed using variance methods. The ROC curve was used to measure the appropriate PI-LL threshold. When considering the effect of age, the patients with Oswestry Disability Index (ODI) 0.8, postoperative sagittal vertical axis (SVA) ≤ 5 cm, postoperative T1 pelvic angle (TPA) ≤ 16° and postoperative global tilt (GT) ≤ 22°, respectively. Regardless of the effect of age, there was a statistical difference in postoperative HRQOL between group 0 and group ++. The PI-LL threshold derived from the ROC curve was 14.4°. Compared with the PI-LL > 14° group, the PI-LL ≤ 14° group achieved a lower postoperative ODI score and a higher postoperative SRS-22 score. Considering the influence of age, the equation for ideal PI-LL was PI-LL = 0.52age + 0.38PI-39.4 (R = 0.509, p = 0.001).ConclusionsPI-LL was an important parameter that affects the postoperative HRQOL of DLS patients. Sufficient LL should be restored during the operation (LL ≥ PI-14°). The appropriate PI-LL value was affected by age. Smaller LL needed to be restored as the age increased.

Extruded ice is a common disease in road engineering in Sichuan-Tibet cold region, which seriously threatens the safety of road construction and operation. Preventing groundwater from being exposed to the surface or the groundwater level being too high can slow down or eliminate the formation of extruded ice. Field investigation and satellite map identification show that extruded ice in Sichuan-Tibet cold region is mainly overflow type. The prevention effects on extruded ice of backfilling with gravelly coarse sand or pebbles to dredge groundwater and laying waterproof geotextiles are analyzed by indoor physical simulation experiments. The results show that extruded ice will gradually form when the frozen depth is lower than the depth of groundwater level. Backfilling seepage layer with gravelly coarse sand or pebbles can accelerate the discharge of groundwater and reduce the pore water pressure effectively. Compared with the untreated slope, the volume of extruded ice is reduced by 85.4% and 93.9% respectively, and the pore water pressure is reduced by 46.2% and 58.1% respectively. By blocking groundwater with waterproof geotextile, the volume of extruded ice is reduced by 97.5%, but the pore pressure will increase. Considering the sufficient pebble (or gravel) materials in Sichuan-Tibet alpine region, it is recommended to use permeable pebble (or gravel) as backfill layer to accelerate groundwater drainage and control extruded ice disease in subgrade slope. And waterproof geotextile is recommended to be laid on backfill layer. The research results can provide reference for the prevention of extruded ice in Sichuan-Tibet traffic roads.

Abstract Background Mesenchymal stem cells (MSCs) possess the potential to differentiate into chondrocytes, which makes them an ideal source for healing cartilage defects. Here, we seek to identify the essential genes participating in MSCs chondrogenesis. Methods Human MSCs were induced for chondrogenesis for 7, 14, and 21 days using a high-density micromass culture system, and RNA was extracted for RNA-seq. Results A total of 6247 differentially expressed genes (DEGs) were identified on day 7, and 85 DEGs were identified on day 14. However, no significant DEGs was identified on day 21. The top 30 DEGs at day 7, including COL9A3, COL10A1, and CILP2, are closely related to extracellular matrix organization. While the top 30 DEGs at day 14 revealed that inflammation-related genes were enriched, including CXCL8, TLR2, and CCL20. We also conducted protein–protein interaction (PPI) networks analysis using the search tool for the retrieval of interacting genes (STRING) database and identified key hub genes, including CXCL8, TLR2, CCL20, and MMP3. The transcriptional factors were also analyzed, identifying the top 5 TFs: LEF1, FOXO1, RORA, BHLHE41, and SOX5. We demonstrated one particular TF, RORA, in promoting early MSCs chondrogenesis. Conclusions Taken together, our results suggested that these DEGs may have a complex effect on MSCs chondrogenesis both synergistically and solitarily.

Abstract The harmonious functioning of growth plate chondrocytes is crucial for skeletogenesis. These cells rely on an appropriate intensity of glycolysis to maintain survival and function in an avascular environment, but the underlying mechanism is poorly understood. Here we show that Hnrnpk orchestrates growth plate development by maintaining the appropriate intensity of glycolysis in chondrocytes. Ablating Hnrnpk causes the occurrence of dwarfism, exhibiting damaged survival and premature differentiation of growth plate chondrocytes. Furthermore, Hnrnpk deficiency results in enhanced transdifferentiation of hypertrophic chondrocytes and increased bone mass. In terms of mechanism, Hnrnpk binds to Hif1a mRNA and promotes its degradation. Deleting Hnrnpk upregulates the expression of Hif1α, leading to the increased expression of downstream glycolytic enzymes and then exorbitant glycolysis. Our study establishes an essential role of Hnrnpk in orchestrating the survival and differentiation of chondrocytes, regulating the Hif1α-glycolysis axis through a post-transcriptional mechanism during growth plate development.

The daylily (Hemerocallis citrina Baroni) flower is a traditional raw food material that is rich in a variety of nutrients. In particular, the content of polysaccharides in daylily is abundant and has been widely used as a functional component in food, cosmetics, medicine, and other industries. However, studies on the structure-effective relationship of daylily flower polysaccharides are still lacking. In view of this, daylily flower polysaccharides were isolated and purified, and their physical and chemical properties, structure, antioxidant activity, and adhesion-promoting effect on probiotics were evaluated. The results showed that a novel water-soluble polysaccharide (DPW) with an average molecular weight (Mw) of 2.224 kDa could be successfully isolated using column chromatography. Monosaccharide composition analysis showed that DPW only comprised glucose and fructose, with a molar ratio of 0.242:0.758. Through methylation and nuclear magnetic resonance (NMR) analysis, it was inferred that DPW belonged to the fructans group with a structure of α-D-Glcp-1→2-β-D-Fruf-1→(2-β-D-Fruf-1)n→. Antioxidant analysis showed that DPW showed strong 2-Phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-Oxide (PTIO-scavenging activity with IC50 of 1.54 mg/mL. DPW of 1.25 to 5 mg/mL could significantly increase the adhesion rate of Lactobacillus acidophilu, Lactobacillus casei, Bifidobacterium adolescentis, and Lactobacillus plantarum on Caco-2 cells. Considering the above results, the present study provides a theoretical basis and practical support for the development and application of daylily polysaccharides as a functional active ingredient.

The wear particle classification algorithm proposed is based on an integrated ResNet50 and Vision Transformer, aiming to address the problems of a complex background, overlapping and similar characteristics of wear particles, low classification accuracy, and the difficult identification of small target wear particles in the region. Firstly, an ESRGAN algorithm is used to improve image resolution, and then the Separable Vision Transformer (SepViT) is introduced to replace ViT. The ResNet50-SepViT model (SV-ERnet) is integrated by combining the ResNet50 network with SepViT through weighted soft voting, enabling the intelligent identification of wear particles through transfer learning. Finally, in order to reveal the action mechanism of SepViT, the different abrasive characteristics extracted by the SepViT model are visually explained using the Grad-CAM visualization method. The experimental results show that the proposed integrated SV-ERnet has a high recognition rate and robustness, with an accuracy of 94.1% on the test set. This accuracy is 1.8%, 6.5%, 4.7%, 4.4%, and 6.8% higher than that of ResNet101, VGG16, MobileNetV2, AlexNet, and EfficientV1, respectively; furthermore, it was found that the optimal weighting factors are 0.5 and 0.5.

Abstract Background Human mesenchymal stem cells (hMSCs) have been proven to have inherent chondrogenic differentiation potential, which appears to be used in cartilage regeneration. Increasing evidence suggests that irisin enhances osteoblast differentiation of MSCs, but little is known about its potential on chondrogenic differentiation. Methods In the study, we investigated the effects of irisin on chondrogenic differentiation of hMSCs using a high-density pellet culture system. The cartilage pellets were evaluated by morphology, and the metabolism of cartilage matrix was detected by qPCR, western blot and immunohistochemistry. Next, RNA-seq was performed to explore the underlying mechanism. Furthermore, using the transduction of plasmid, miRNAs mimics and inhibitor, the activation of Rap1/PI3K/AKT axis, the expression level of SIPA1L2, and the functional verification of miR-125b-5p were detected on day 7 of chondrogenic differentiation of hMSCs. Results Compared with the controls, we found that irisin treatment could significantly enhance the chondrogenic differentiation of hMSCs, enlarge the induced-cartilage tissue and up-regulate the expression levels of cartilage markers. RNA-seq indicated that irisin activated the Rap1 and PI3K/AKT signaling pathway, and the lower expression level of SIPA1L2 and the higher expression level of miR-125b-5p were found in irisin-treated group. Further, we found that irisin treatment could up-regulate the expression level of miR-125b-5p, targeting SIPA1L2 and consequently activating the Rap1/PI3K/AKT axis on the process of chondrogenic differentiation of hMSCs. Conclusions Collectively, our study reveals that irisin can enhance chondrogenic differentiation of hMSCs via the Rap1/PI3K/AKT pathway, suggesting that irisin possesses prospects in cartilage regeneration.

Background The continuous occurrence of Kummell's disease is extremely rare in clinical practice, and its treatment is difficult. The study aimed to present a rare case of consecutive Kummell's disease combined with Parkinson's disease (PD) and experienced internal fixation failure. Case presentation A 69‐year‐old female patient had a history of PD for 10 years, and was treated by posterior decompression, fixation, and fusion because of Kummell's disease of T12 with neurological damage. The patient's back pain and lower limb pain were significantly improved after surgery. Twenty‐two months later, the patient was rehospitalized for Kummell's disease of L4 with neuropathic pain of left lower extremity. She received almost identical surgical procedures as T12 lesion, and the difference was no L4 vertebroplasty preformed due to the fact that the L4 vertebrae collapse was not obvious, the intravertebral vacuum cleft (IVC) range was small, and the pedicle screw fixation strength was high. The pain symptoms were significantly relieved after operation. Unfortunately, there was a complication of internal fixation failure that occurred a month later, and a revision operation was carried out. Conclusion Osteoporosis combined with PD may lead patients to become prone to consecutive Kummell's disease, and patients are prone to experience failure of internal fixation. Bone cement filling of vertebral IVC and effective support of anterior vertebral column are very important procedures to ensure the clinical efficacy of treating Kummell's disease.

Low back pain is one of the top disorders that leads to disability and affects disability-adjusted life years (DALY) globally. Intervertebral disc degeneration (IDD) and subsequent discogenic pain composed major causes of low back pain. Recent studies have identified several important risk factors contributing to IDD's development, such as inflammation, mechanical imbalance, and aging. Based on these etiology findings, three categories of animal models for inducing IDD are developed: the damage-induced model, the mechanical model, and the spontaneous model. These models are essential measures in studying the natural history of IDD and finding the possible therapeutic target against IDD. In this review, we will discuss the technical details of these models, the duration between model establishment, the occurrence of observable degeneration, and the potential in different study ranges. In promoting future research for IDD, each animal model should examine its concordance with natural IDD pathogenesis in humans. We hope this review can enhance the understanding and proper use of multiple animal models, which may attract more attention to this disease and contribute to translation research.

Abstract Background With the widespread use of the posterior surgery, more and more surgeons chose posterior surgery to treat thoracic and lumbar tuberculosis. But others still believed that the anterior surgery is more conducive to eradicating the lesions, and easier to place larger bone pieces for bone graft fusion. We compared the clinical and radiological outcomes of anterior and posterior surgical approaches and presented our views. Methods This study included 52 thoracic and lumbar tuberculosis patients at Sun Yat-sen Memorial Hospital from January 2010 to June 2018. All cases underwent radical debridement, nerve decompression, intervertebral bone graft fusion and internal fixation. Cases were divided into anterior group (24 cases) and posterior group (28 cases). Statistical analysis was used to compare the clinical effectiveness, radiological outcomes, complications and other related information. Results Patients in the anterior group and the posterior group were followed up for an average of 27.4 and 22.3 months, respectively. There were no statistically significant differences between groups in the preoperative, postoperative and last follow-up VAS score, ASIA grade and Cobb angle of local kyphosis. Moreover, there were no statistically significant differences in the improvement of neurological function, loss of kyphotic correction, total incidence of complications, operative time, intraoperative blood loss and hospital stay between the two groups (P > 0.05). But there was greater correction of kyphosis, earlier bone fusion, lower incidence of poor wound healing, less interference with the normal spine and less internal fixation consumables and medical cost in the anterior group (P

This paper is devoted to an initial-boundary value problem for a class of $ p $-Kirchhoff type parabolic equations. Firstly, we consider this problem with a general nonlocal coefficient $ M(\|\nabla u\|_p^p) $ and a general nonlinearity $ k(t)f(u) $. A new finite time blow-up criterion is established, also, the upper and lower bounds for the blow-up time are derived. Secondly, we deal with the case that $ M(\|\nabla u\|_p^p) = a+b\|\nabla u\|_p^p $, $ k(t)\equiv1 $ and $ f(u) = |u|^{q-1}u $, which was considered by Li and Han [Math. Model. Anal. 2019; 24: 195-217] only for $ q > 2p-1 $. The threshold results for the existence of global and finite time blow-up solutions to this problem are obtained for the case $ 1 < q\leq 2p-1 $, which, together with the results given by Li and Han, shows that $ q = 2p-1 $ is critical for the existence of finite time blow-up solutions to this problem. These results partially generalize and extend some recent ones in previous literature.

Abstract In recent years, with the in-depth research on spinal tuberculosis, posterior surgery alone has been praised highly by more and more surgeons due to the better correction of kyphosis, better maintenance of spinal physiological curvature, smaller surgical trauma and fewer surgical complications. However, there is currently lack of relevant reports about the efficacy of posterior surgery alone in the treatment of tuberculosis in the T4–6 segments. This study aimed to evaluate the clinical study efficacy and feasibility of one-stage posterior-only surgical treatment for thoracic spinal tuberculosis in the T4–6 segments. 67 patients with tuberculosis in T4–6 segments who underwent one-stage posterior-only surgery were included in this study. The clinical efficacy was evaluated using statistical analysis based on the data about erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Oswestry Dability Index (ODI) score, Visual Analogue Scale (VAS) score and Cobb angle before surgery, after surgery and at the last follow-up. All patients completed fusion during the follow-up period of 6–9 months. ESR and CRP were returned to normal for all patients at 6 months follow-up. In the meanwhile, among the 27 patients combined with neurological impairment, neurological functions of 22 cases (81.48%) recovered completely at the last follow-up (P

Syringa oblata is a high ornamental value tree owing to its elegant colors, unique aromas and wide adaptability, however, studies on the molecular mechanism underlying the formation of its ornamental traits are still lacking. Here, we presented a chromosome-scale genome assembly of S. oblata and the final genome size was 1.11 Gb with a contig N50 of 4.75 Mb, anchored on 23 chromosomes and was a better reference for S. oblata transcriptome assembly. Further by integrating transcriptomic and metabolic data, it was concluded that F3H, F3’H, 4CL and PAL, especially the F3’H, were important candidates involved in the formation of floral color differences among S. oblata individuals. Genome-wide identification and analysis revealed that the TPS-b subfamily was the most abundant subfamily of TPS family in S. oblata, which together with the CYP76 family genes determined the formation of the major floral volatiles of S. oblata. Overall, our results provide an important reference for mechanistic studies on the main ornamental traits and molecular breeding in S. oblata.

Abstract Osteoarthritis (OA) is characterized by cartilage destruction, chronic inflammation, and local pain. Evidence showed that retinoic acid receptor-related orphan receptor-α (RORα) is crucial in cartilage development and OA pathogenesis. Here, we investigated the role and molecular mechanism of RORα, an important member of the nuclear receptor family, in regulating the development of OA pathologic features. Investigation into clinical cartilage specimens showed that RORα expression level is positively correlated with the severity of OA and cartilage damage. In an in vivo OA model induced by anterior crucial ligament transaction, intra-articular injection of si-Rora adenovirus reversed the cartilage damage. The expression of cartilage matrix components type II collagen and aggrecan were elevated upon RORα blockade. RNA-seq data suggested that the IL-6/STAT3 pathway is significantly downregulated, manifesting the reduced expression level of both IL-6 and phosphorylated STAT3. RORα exerted its effect on IL-6/STAT3 signaling in two different ways, including interaction with STAT3 and IL-6 promoter. Taken together, our findings indicated the pivotal role of the RORα/IL-6/STAT3 axis in OA progression and confirmed that RORα blockade improved the matrix catabolism in OA chondrocytes. These results may provide a potential treatment target in OA therapy.

Study DesignRetrospective analysis.ObjectiveTo evaluate bone quality and investigate asymmetrical development of the thoracic vertebral body in adolescent idiopathic scoliosis (AIS) based on Hounsfield unit (HU) measurements obtained from computed-tomography (CT) scans.Summary of Background DataHU value demonstrated higher reliability and accuracy than the traditional method, indicating that they could be used to individually evaluate and effectively assess the bone quality of every vertebra in the CT films.MethodsTotal 30 AIS patients classified as Lenke Type 1A and 30 paired controls were included in this study. Regions of interest for HU value were measured on three horizontal images of the thoracic vertebrae. HU measurements of the whole vertebral body in each vertebra were obtained. Using HU value, we separately measured the concave and convex sides of each vertebral body in patients' group, as well as within the left and right sides in controls.ResultsIn controls, the mean HU value of T1–T12 thoracic vertebral bodies was 240.03 ± 39.77, with no statistical differences among different levels. As for AIS patients, in the structural curve, the apical region had a significantly lower HU compared with the other regions, and asymmetrical change was found between the concave and convex sides, most significantly in the apical region. In the non-structural curve, the average HU value was 254.99 ± 44.48, and no significant difference was found either among the different levels of vertebrae or between the concave and convex sides.ConclusionsAbnormal and asymmetrical changes in bone quality of the thoracic vertebral body in patients with Lenke 1A AIS were indicated. Low bone quality in the convex side of the structural curve indicated stronger internal fixation in surgery to correct the deformity.

Two-dimensional (2D) tumor model has always poorly predicted drug response of animal model due to the lack of recapitulation of tumor microenvironment. Establishing a biomimetic, controllable, and cost-effective three-dimensional (3D) model and large-scale validation of its in vivo predictivity has shown promise in bridging the gap between the 2D tumor model and animal model. Here, we established a matrigel-based 3D micro-tumor model on an array chip for large-scale anticancer drug evaluation. Compared with the 2D tumor model, the 3D tumor model on the chip showed spheroid morphology, slower proliferation kinetics, and comparable reproducibility. Next, the results of the chemotherapeutic evaluation from 18 drugs against 27 cancer cell lines showed 17.6% of drug resistance on the 3D tumor model. Moreover, the evaluation results of targeted drugs showed expected sensitivity and higher specificity on the 3D tumor model compared with the 2D model. Finally, the evaluation results on the 3D tumor model were more consistent with the in vivo cell-derived xenograft model, and excluded 95% false-positive results from the 2D model. Overall, the matrigel-based 3D micro-tumor model on the array chip provides a promising tool to accelerate anticancer drug discovery.

Colorectal cancer (CRC) is one of the most common and deadly cancers, and the incidence of CRC is on the rise. Due to the lack of early diagnosis method and high metastasis of the disease, the prognosis of CRC remains very poor. Exploring the underlying molecular mechanisms of CRC is very necessary for effective therapy. In this study, we investigated the function of circBANP in CRC. The results showed that circBANP was elevated in both CRC tissues and cells and its level positively correlated with the stage of CRC. Knockdown of circBANP greatly suppressed the epithelial-mesenchymal transition (EMT) process and CRC cell proliferation, migration, and invasion. In addition, knockdown of circBANP inhibited CRC tumor growth and metastasis in vivo. Further, circBANP directly bound to let-7d-5p and regulated CRC development via acting as a let-7d-5p sponge. Let-7d-5p directly targeted HMGA1 and thus circBANP/let-7d-5p regulated Wnt/β-catenin signaling via HMGA1. Collectively, circBANP promotes CRC development and metastasis via acting as a let-7d-5p sponge to regulate HMGA1/Wnt/β-catenin signaling, providing a potential biomarker and therapeutic target for the management of CRC.

Abstract Background Pre-existing degeneration of adjacent segment is an important risk factor for adjacent-segment degeneration (ASD), but only limited and controversial studies have addressed its management. Methods We retrospectively analyzed patients with symptomatic degeneration of the L5/S1 segment warranting surgical interference and severe asymptomatic degeneration of the L4/5 segment. Of these patients, those who underwent interbody fusion of the causative (L5/S1) segment and distraction of the intervertebral space and facet fusion of the adjacent L4/5 segment were included in Group A (n = 103), while those who underwent interbody fusion of both the L5/S1 and L4/5 segments were included in Group B (n = 81). Clinical and radiographic outcomes were evaluated. Results Mean follow-up time was 58.5 months (range, 48–75 months). We found no significant difference in clinical outcomes or incidence of ASD in the L3/4 segment between Groups A and B. Compared with Group B, Group A experienced less bleeding (315 ± 84 ml vs. 532 ± 105 ml), shorter operation time (107 ± 34 min vs. 158 ± 55 min) and lower costs (US $13,830 ± $2640 vs. US $16,020 ± $3380; P

Abstract Background Little is known about the implications of circRNAs in the effects of melatonin (MEL) on bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation and osteoporosis (OP) progression. The aim of our study was to investigate circRNAs in MEL-regulated BMSC differentiation and OP progression. Methods BMSC osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red, and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade was validated for the osteogenic differentiation of BMSCs by CCK-8, qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on OP development were tested in murine OP model. Results MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 had no effect on proliferation while promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSC osteogenic differentiation induced by MEL, but proliferation of BMSCs induced by MEL had no change whether circ_0003865 was overexpression or not. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSC osteogenic differentiation was enhanced by miR-3653-3p overexpression while BMSC proliferation was not affected. By contrast, miR-3653-3p silencing mitigated the promoted BMSC osteogenic differentiation caused by circ_0003865 silencing, but had no effect on proliferation. Finally, circ_0003865 silencing repressed OP development in mouse model. Conclusion MEL promotes BMSC osteogenic differentiation and inhibits OP pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.

N-glycosylation is a physiologically vital post-translational modification of proteins in eukaryotic organisms. Initial work on Haemonchus contortus – a blood-sucking nematode of ruminants with a broad geographical distribution – has shown that this parasite harbors N-glycans with exclusive chitobiose modifications. Besides, several immunogenic proteins (e.g., amino- and metallo-peptidases) are known to be N-glycosylated in adult worms. However, an informative atlas of N-glycosylation in H. contortus is not yet available. Herein, we report 291 N-glycosylated proteins with a total of 425 modification sites in the parasite. Among them, many peptidase families (e.g., peptidase C1 and M1) including potential vaccine targets were enriched. Notably, the glycan-rich conjugates are distributed primarily in the intestine and gonads of adult worms, and consequently hidden from the host’s immune system. Collectively, these data provide a comprehensive atlas of N-glycosylation in a prevalent parasitic nematode while underlining its significance for infection, immunity and prevention.

ObjectiveOsteoporosis (OP), clinically featured with a low bone mineral density (BMD) and high risk of bone fracture, has become a major risk factor of disability and death in the elders, especially in postmenopausal women. The gut microbiome (GM) is thought to be implicated in bone metabolism. Herein, we clarified the composition signature and gene functional profile of GM in older people with normal and low BMD.Design and MethodsA total of 455 participants underwent the BMD measurement and biochemical detection. GM analysis was further performed on 113 cases of postmenopausal women and men aged over 50, including both 16S rRNA and metagenomic sequencing.ResultsGenerally, the BMD value was significantly lower in the older age groups, especially in the postmenopausal women. Consistently, we observed obvious vitamin D deficiency or insufficiency in females (compared to the male, P < 0.0001). The results from 16S rRNA sequencing revealed higher numbers of OTUs and diversity indexes in females than in males. The abundance in composition of Firmicutes and Clostridiales were correlated with the BMD values in females. LEfSe analysis discovered several enriched bacteria taxons in OP and normal control (NC) subgroups. A positive correlation between the number of genes and BMD values was observed in females based on metagenomic sequencing analysis. Furthermore, we identified the connecting modules among the GM composition – gene functional signature – BMD value/T score in both females and males.ConclusionsThis study provides evidences upon which to understand the mechanisms of the effects of GM on bone health, consequently revealing the physiology status and potential diagnostic/therapeutic targets based on GM for OP and postmenopausal osteoporosis (PMOP). Besides, the status of vitamin D deficiency or insufficiency need to be concerned and improved in the Chinese people.

Abstract Background Long bones of limbs are formed through endochondral bone formation, which depends on the coordinated development of growth plates. Our previous studies have demonstrated that dysfunction of mitogen-activated protein kinase 7 (MAPK7) can cause skeletal dysplasia. However, little is known about the role of MAPK7 in the regulation of proliferation and differentiation of chondrocytes during growth plate development. Results Ablation of MAPK7 expression in chondrocytes led to growth restriction, short limbs and bone mass loss in postnatal mice. Histological studies revealed that MAPK7 deficiency increased the apoptosis and decreased the proliferation of chondrocytes in the center of the proliferative layer, where the most highly hypoxic chondrocytes are located. Accordingly, hypertrophic differentiation markers were downregulated in the central hypertrophic layer, beneath the site where abnormal apoptosis was observed. Simultaneously, we demonstrated that hypoxic adaptation and hypoxia-induced activation of hypoxia-inducible factor 1 subunit α (HIF1α) were impaired when MAPK7 could not be activated normally in primary chondrocytes. Concomitantly, vascular invasion into epiphyseal cartilage was inhibited when Mapk7 was deleted. Conclusions We demonstrated that MAPK7 is necessary for maintaining proliferation, survival, and differentiation of chondrocytes during postnatal growth plate development, possibly through modulating HIF1α signaling for adaptation to hypoxia. These results indicate that MAPK7 signaling might be a target for treatment of chondrodysplasia.

Abstract Background Acetylacetone is a commercially bulk chemical with diverse applications. However, the traditional manufacturing methods suffer from many drawbacks such as multiple steps, harsh conditions, low yield, and environmental problems, which hamper further applications of petrochemical-based acetylacetone. Compared to conventional chemical methods, biosynthetic methods possess advantages such as being eco-friendly, and having mild conditions, high selectivity and low potential costs. It is urgent to develop biosynthetic route for acetylacetone to avoid the present problems. Results The biosynthetic pathway of acetylacetone was constructed by reversing its biodegradation route, and the acetylacetone was successfully produced by engineered Escherichia coli (E. coli) by overexpression of acetylacetone-cleaving enzyme (Dke1) from Acinetobacter johnsonii. Several promising amino acid residues were selected for enzyme improvement based on sequence alignment and structure analysis, and the acetylacetone production was improved by site-directed mutagenesis of Dke1. The double-mutant (K15Q/A60D) strain presented the highest acetylacetone-producing capacity which is 3.6-fold higher than that of the wild-type protein. Finally, the strain accumulated 556.3 ± 15.2 mg/L acetylacetone in fed-batch fermentation under anaerobic conditions. Conclusions This study presents the first intuitive biosynthetic pathway for acetylacetone inspired by its biodegradation, and shows the potential for large-scale production.

The development of convolutional neural networks has promoted the progress of computer-aided diagnostic systems. Details in medical image, such as the texture and tissue structure, are crucial features for diagnosis. Therefore, large input images combined with deep convolution neural networks are adopted to boost the performance in recent research of chest X-ray diagnosis. Meanwhile, due to the variable sizes of thoracic diseases, many researchers have worked to introduce additional module to capture multi-scale feature of images in CNN. However, these efforts hardly consider the computational costs of large inputs and introduced additional modules. This paper aims to automatically diagnose diseases on chest X-rays images quickly and effectively. We propose the multi-kernel depthwise convolution(MD-Conv) which contains depthwise convolution kernels with different filter sizes in one depthwise convolution layer. MD-Conv has high calculation efficiency and few parameters. Because its ability to learn multi-scale feature based on the multi-size kernels, it is appropriate for medical images diagnosis tasks in which abnormalities varied in sizes. In addition, larger depthwise convolution kernels are adopted in MD-Conv to obtain a larger receptive field efficiently, which can ensure sufficient receptive field for high resolution inputs. MD-Conv can be easily applied in modern lightweight networks to replace the normal depthwise convolution layer. We conduct experiments on the Chest X-ray 14 Dataset, which is the largest available chest x-ray dataset, and obtain competitive results. We also evaluate the MD-Conv on the new released dataset for pediatric pneumonia diagnosis. We obtain a better performance of 98.3% AUC than original paper (96.8%) for recognize pneumonia versus normal. Meanwhile we compare the FLOPs and Params of different models to show their efficiency for chest X-rays recognition.

Intervertebral disc degeneration (IDD) is a degenerative disease that is characterized by decreased matrix synthesis and extra degradation, nucleus pulposus cells (NPCs) apoptosis, and infiltration of inflammatory factors. Aloin, a colored compound from aloe plants, has been shown to be effective against skeletal degenerative diseases, but it is unclear whether it is protective against IDD. Herein, we investigated the role of aloin in NPCs. In our study, the upregulation of proinflammatory factors, apoptosis, and unbalanced matrix metabolism were observed in degenerative NP tissues. We found that aloin had a curative effect on extracellular matrix metabolism and apoptosis in TNF-alpha- (TNF-α-) treated NPCs by inhibiting oxidative stress and the proinflammatory factor expression. Further investigation revealed that aloin treatment suppressed the TAK1/NF-κB pathway. Moreover, the expression level of the NLPR3 inflammasome was downregulated after aloin treatment in TNF-α-treated NPCs. In summary, our results demonstrated that aloin treatment can reverse TNF-α-induced unbalanced matrix metabolism and apoptosis of NPCs via the TAK1/NF-κB/NLRP3 axis. This study supports that aloin can be a promising therapeutic agent for IDD.

Many unique chemical metabolites with significant antitumor activities have been isolated from Garcinia species and have become a leading hotspot of antitumor research in recent years. The aim of this study was to identify bioactive compounds from different plant parts (leaf, branch, stem bark, fruit, and seed) of G. xanthochymus through combining LC-MS-based metabolomics with cytotoxicity assays. As a result, 70% methanol seed extract exerted significant cytotoxic effects on five human cancer cell types (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480). LC-MS-based metabolomics analysis was used, including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), in order to identify 12 potential markers from seed extract that may relate to bioactivity. LC-MS guidance isolated the markers to obtain three compounds and identified new isopentenyl phloroglucinols (1–3, named garxanthochin A–C), using spectroscopic methods. Among them, garxanthochin B (2) demonstrated moderate inhibitory activities against five human cancer cell types, with IC50 values of 14.71~24.43 μM. These findings indicate that G. xanthochymus seed has significant cytotoxic activity against cancer cells and garxanthochin B has potential applications in the development of antitumor-led natural compounds.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system, listed as the second cause of cancer-related deaths worldwide. S100 Calcium Binding Protein A16 (S100A16) is an acidic calcium-binding protein associated with several types of tumor progression. However, the function of S100A16 in GC is still not very clear. In this study, we analyzed S100A16 expression with the GEPIA database and the UALCAN cancer database. Meanwhile, 100 clinical GC samples were used for the evaluation of its role in the prognostic analysis. We found that S100A16 is significantly upregulated in GC tissues and closely correlated with poor prognosis in GC patients. Functional studies reveal that S100A16 overexpression triggers GC cell proliferation and migration both in vivo and in vitro; by contrast, S100A16 knockdown restricts the speed of GC cell growth and mobility. Proteomic analysis results reveal a large S100A16 interactome, which includes ZO-2 (Zonula Occludens-2), a master regulator of cell-to-cell tight junctions. Mechanistic assay results indicate that excessive S100A16 instigates GC cell invasion, migration, and epithelial-mesenchymal transition (EMT) via ZO-2 inhibition, which arose from S100A16-mediated ZO-2 ubiquitination and degradation. Our results not only reveal that S100A16 is a promising candidate biomarker in GC early diagnosis and prediction of metastasis, but also establish the therapeutic importance of targeting S100A16 to prevent ZO-2 loss and suppress GC metastasis and progression.

Abstract Background Transpedicular intracorporeal cement augmentation (TCA) with short segmental posterior instrumentation (SSPI), which provides an ideal immediate analgesic effect and long-term reconstructive stability, is thought to be a sensible advancement to the operative strategy in treating osteonecrosis of the vertebral body (ONV). However, long-term follow-up studies about the treatment are scarce. Methods Forty-six ONV patients (22 males and 24 females, mean age of 62.8 ± 7.11 years) underwent TCA with SSPI were retrospectively analyzed. During follow-up, clinical outcomes, such as the Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI) score, were evaluated, as well as radiologic outcomes, such as the average vertebral height and kyphotic angle. Results A total of 36 patients completed a follow-up period of at least 5 years (mean follow-up period of 67 ± 4.2 months). Among them, seven patients experienced complications, i.e., pneumonia (2/36, 5.56%), screw loosening (2/36, 5.56%), moderate hematoma in the subcutaneous tissue (1/36, 2.78%), and cement leakage (2/36, 5.56%). Compared to the preoperative score, the mean VAS score was significantly reduced 6 months postoperatively (P 0.05). The mean ODI score exhibited a comparable trend. Regarding the radiologic evaluation, the mean kyphotic angle and average vertebral body height were significantly corrected postoperatively (both P

Intervertebral disc degenerative disease (IDD) is the most common degenerative spine disease, which leads to chronic low back pain and symptoms in the lower extremities. In this study, we found that RORα, a member of the retinoid-related orphan receptor family, is significantly elevated in nucleus pulposus tissue in IDD patients. The elevation of RORα is associated with increased apoptosis of nucleus pulposus (NP) cells. Therefore, we applicated a well-established inverse agonist of RORα, SR3335, to investigate its role in regulating NP cell metabolism and apoptosis. To further investigate the mechanism that SR3335 regulates the pathogenesis of IDD in vitro, tumor necrosis factor alpha (TNF-α) stimulation was used in human NP cells to mimic the hostile environment that leads to degeneration. We found that SR3335 treatment reversed the trend of increased apoptosis in NP cells induced by TNF-α treatment. Next, TNF-α treatment upregulated the expression of type II collagen and aggrecan and downregulated MMP13 (matrix-degrading enzyme matrix metalloproteinase 13) and ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4). However, these effects were reversed after SR3335 treatment. Furthermore, we find that SR3335 mediated the effect in NP cells by regulating the YAP signaling pathway, especially by affecting the phosphorylation state of YAP. In conclusion, the reduction of matrix degradation enzymes and apoptosis upon SR3335 treatment suggests that SR3335 is a promising drug in reversing the deleterious microenvironment in IDD patients.

Sepsis was characterized by systemic inflammatory response and multisystem organ dysfunction, refering to the activation of inflammatory and oxidative stress pathways. Estrogen has been shown to have anti-inflammatory and antioxidant effects as well as extensive organ protective role. However, whether estrogen alleviates sepsis-induced liver injury and the mechanisms involved remain unknown. Septic mice were constructed by intraperitoneal injection lipopolysaccharide, and the effect of estrogen on liver injury was investigated. Furthermore, the roles of NLRP3 inhibitor MCC950 and mitochondrial ROS specific scavenger Mito-tempo, on the liver injury were explored in septic mice. Female septic mice exhibited liver damage with increased serum AST and ALT level as well as the existence of extensive necrosis, and which was more serious in male septic mice. Moreover, Ovariectomy (OVX) aggravated sepsis-induced liver damage and activation of pyroptosis signaling pathway, which was alleviated by estrogen as evidenced by decreased serum AST, ALT level and number of infiltrating inflammatory cell, as well as protein expression related to pyroptosis. OVX aggravated mitochondrial dysfunction and liver injury in septic mice was also partly reversed by Mito-tempo and MCC950. These results demonstrated that estrogen protected against sepsis-induced liver damage through alteration of mitochondrial function and activation of inflammatory-mediated pyroptosis signaling pathway.

Abstract Background Osteoarthritis (OA) is a widespread arthritic disease and a primary cause of disability. Increasing evidence suggests that inflammation has a pivotal part in its pathogenesis. Interleukin-1β (IL-1β) is a primary mediator of local inflammatory processes in OA. Current therapies for OA mainly focus on the symptoms of the advanced stage of the disease. The possible utilization of bone marrow mesenchymal stem cells (BMSCs) to regenerate cartilage is an appealing method, but in the case of OA requires chondrogenesis to take place within an inflamed environment. Our previous study showed that melatonin (MLT) can promote chondrogenic differentiation of MSCs, but whether MLT can rescue IL-1β-impaired chondrogenesis in human BMSCs has not yet been established. MLT, which can have anti-inflammatory and prochondrogenic effects, has demonstrated potential in defeating IL-1β-induced inhibition of chondrogenesis and further study should be conducted. Methods Human bone marrow-derived MSCs were separated and cultured based on our system that was already documented. A high-density micromass culture system was used for the chondrogenic differentiation of human BMSCs, which was also described previously. Human BMSCs were induced for chondrogenesis for 7, 14, and 21 days with the treatment of IL-1β and MLT. The cultured cartilage pellets were then evaluated by morphology, extracellular matrix accumulation, and chondrogenic, metabolic, and apoptotic marker expression. Furthermore, cell apoptosis was assessed by TUNEL assay. The phosphorylation level P65 and IκBα of the NF-κB pathway activity was explored on day 21 of chondrogenic differentiation of BMSCs. Results The current evaluation showed that MLT can save IL-1β-impaired chondrogenesis of human BMSCs in different aspects. Firstly, MLT can restore the chondrogenic pellet size, and rescue matrix synthesis and accumulation. Secondly, MLT can upregulate chondrogenic marker COL2A1 expression at both mRNA and protein levels, and also regulate the expression levels of other chondrogenic markers like ACAN, SOX9, and COL10A1 in the presence of IL-1β. Thirdly, MLT can maintain the metabolic balance of the chondrogenic process by suppressing expression of catabolic genes, such as MMP, MMP13, and ADAMTS4. Furthermore, MLT can subdue IL-1β-induced cell apoptosis of BMSCs throughout chondrogenesis. Meanwhile, MLT suppressed the phosphorylation level of P65 and IκBα, which were elevated by IL-1β treatment, indicating that MLT can attenuate the IL-1β-induced activation of NF-κB signaling. Conclusion The current evaluation showed that MLT can save IL-1β-impaired chondrogenesis of human BMSCs by restoring the pellet size and matrix accumulation, and maintaining the metabolic balance, reducing cell apoptosis. Our study also showed that MLT can attenuate the IL-1β-induced activation of the NF-κB signaling pathway, which is the most important pathway downstream of IL-1β, and plays a crucial role in inflammation, apoptosis, and metabolism. Thus, MLT has prospects for treating OA due to its multifaceted functions, such as mitigating inflammation, maintaining metabolic balance, and mitigating apoptosis.

Abstract Recurrent complex spinal tuberculosis accompanied by sinus tract formation is one of the most common and complex types of recurrent tuberculosis. To date, only very few studies have reported the strategies and effectiveness of surgical treatments on postoperative recurrent spinal tuberculosis accompanied by sinus tract formation. In this study, 21 recurrent patients out of 87 patients with complex spinal tuberculosis were reviewed. The data of the patients, including age, gender, existence of drug-resistant mycobacterium tuberculosis, postoperative standard chemotherapy, completeness of lesion debridement, reconstruction of the spinal stability, nutritional status, accompaniment by tuberculosis in other regions, timing of the operations, and areas of the lesions, were collected for single- and multiple-factor analyses. The clinical outcomes were evaluated by long-term follow-ups. The results showed that 7 factors were significantly associated with postoperative recurrence of complex spinal tuberculosis accompanied by sinus tract formation. This suggested that when we treat complex spinal tuberculosis, we should pay more attention to these seven indicators to avoid postoperative recurrence, and our clinical outcomes suggested that it is difficult to treat recurrent complicated spinal tuberculosis combined with sinus tract formation. The key for successful surgical treatment includes effective chemotherapy, radical debridement and proper reconstruction of spinal stability.

Lithium resources face risks of shortages owing to the rapid development of the lithium industry. This makes the efficient production and recycling of lithium an issue that should be addressed immediately. Lithium bromide is widely used as a water-absorbent material, a humidity regulator, and an absorption refrigerant in the industry. However, there are few studies on the recovery of lithium from lithium bromide after disposal. In this paper, a bipolar membrane electrodialysis (BMED) process is proposed to convert waste lithium bromide into lithium hydroxide, with the generation of valuable hydrobromic acid as a by-product. The effects of the current density, the feed salt concentration, and the initial salt chamber volume on the performance of the BMED process were studied. When the reaction conditions were optimized, it was concluded that an initial salt chamber volume of 200 mL and a salt concentration of 0.3 mol/L provided the maximum benefit. A high current density leads to high energy consumption but with high current efficiency; therefore, the optimum current density was identified as 30 mA/cm2. Under the optimized conditions, the total economic cost of the BMED process was calculated as 2.243 USD·kg−1LiOH. As well as solving the problem of recycling waste lithium bromide, the process also represents a novel production methodology for lithium hydroxide. Given the prices of lithium hydroxide and hydrobromic acid, the process is both environmentally friendly and economical.

Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term in vitro culture results in loss of MSC stemness. The inflammation that occurs at stem cell transplant sites (such as that resulting from TNF-α) is a contributing factor for stem cell treatment failure. Currently, there is little evidence regarding the protective role of melatonin with regard to the negative effects of TNF-α on the stemness of MSCs. In this study, we report a melatonin-based method to reduce the inflammatory effects on the stemness of bone marrow mesenchymal stem cells (BMMSCs). The results of colony formation assays, Alizarin red staining, western blotting, and reverse transcription-polymerase chain reactions suggest that melatonin can reverse the inflammatory damage caused by TNF-α treatment in the third, seventh, and tenth generations of primary BMMSCs (vs. control and the TNF-α-treated group). Meanwhile, a detailed analysis of the molecular mechanisms showed that the melatonin receptor and YAP signaling pathway are closely related to the role that melatonin plays in negative inflammatory effects against BMMSCs. In addition, in vivo experiments showed that melatonin could reverse the damage caused by TNF-α on bone regeneration by BMMSCs in nude mice. Overall, our results suggest that melatonin can reverse the loss of stemness caused by inflammatory factor TNF-α in BMMSCs. Our results also provide a practical strategy for the application of BMMSCs in tissue engineering and cell therapy.

Lithium carbonate is an important chemical raw material that is widely used in many contexts. The preparation of lithium carbonate by acid roasting is limited due to the large amounts of low-value sodium sulfate waste salts that result. In this research, bipolar membrane electrodialysis (BMED) technology was developed to treat waste sodium sulfate containing lithium carbonate for conversion of low-value sodium sulfate into high-value sulfuric acid and sodium hydroxide. Both can be used as raw materials in upstream processes. In order to verify the feasibility of the method, the effects of the feed salt concentration, current density, flow rate, and volume ratio on the desalination performance were determined. The conversion rate of sodium sulfate was close to 100%. The energy consumption obtained under the best experimental conditions was 1.4 kWh·kg−1. The purity of the obtained sulfuric acid and sodium hydroxide products reached 98.32% and 98.23%, respectively. Calculated under the best process conditions, the total process cost of BMED was estimated to be USD 0.705 kg−1 Na2SO4, which is considered low and provides an indication of the potential economic and environmental benefits of using applying this technology.

Cervicothoracic spinal tuberculosis is a rare disease. Due to its difficult and challenging surgical exposure, its surgical treatment approach remains inconclusive. Long-term follow-up studies to address this puzzling issue are rarely seen in the literature. The purpose of this study was to explore the selection of surgical treatment approaches for cervicothoracic spinal tuberculosis through a 10-year case review.From January 2003 to January 2013, 45 patients suffering from cervicothoracic spinal tuberculosis were treated surgically. According to the relation between the tuberculosis lesion segments and the suprasternal notch on sagittal MRI, 19 patients were treated with a single-stage anterior debridement, fusion and instrumentation approach, and the other 26 patients were treated with a single-stage anterior debridement and fusion, posterior fusion and instrumentation approach. The clinical efficacy was evaluated using statistical analysis based on the Cobb angle of kyphosis, the Neck Disability Index (NDI) and the Japanese Orthopedic Association (JOA) scoring system. The neurofunctional recovery was assessed by the American Spinal Injury Association (ASIA) system.All patients were followed up for 6.6 years on average (range 3-13 years). No instrumentation loosening, migration or breakage was observed during the follow-up. The kyphosis angle and NDI and JOA scores were significantly changed from preoperative values of 34.7±6.8°, 39.6±4.6 and 10.7±2.8 to postoperative values of 10.2±2.4°, 11.4±3.6 and 17.6±2.4, respectively (p

BackgroundBrucella canis is a pathogenic bacterium that causes brucellosis in dogs, and its zoonotic potential has been increasing in recent years. B. canis is a rare source of human brucellosis in China, where Brucella melitensis has been the major pathogen associated with human brucellosis outbreaks. In late 2011, a case of a B. canis infection was detected in a human patient in Zhejiang Province, China. To compare the genotypes between strains of B. canis isolated from the patient and from dogs, a multiple-locus variable-number tandem-repeat analysis (MLVA-16) was performed. In addition, the lipopolysaccharide-synthesis-related genes were analyzed with the B. canis reference strain RM6/66.Results32 B. canis strains were divided into 26 genotypes using MLVA-16 [Hunter-Gaston Diversity Index (HGDI) = 0.976]. The HGDI indexes for various loci ranged between 0.000 and 0.865. All four Hangzhou isolates were indistinguishable using panel 1 (genotype 3) and panel 2A (genotype 28). However, these strains were distinctly different from other isolates from Beijing, Jiangsu, Liaoning, and Inner Mongolia at Bruce 09. The emergence of a human B. canis infection was limited to an area. Comparative analysis indicated B. canis from canines and humans have no differences in lipopolysaccharide-synthesis locus.ConclusionThe comprehensive approaches have been used to analyze human and canine B. canis isolates, including molecular epidemiological and LPS genetic characteristics. Further detailed analysis of the whole genomic sequencing will contribute to understanding of the pathogenicity of B. canis in humans.

This article is devoted to the study of the existence of weak solutions to an initial and boundary value problem for a parabolic p(x)-Laplace equation with convection term. Using the De Giorgi iteration technique, the authors establish the critical a priori L-infinity estimates and thus prove the existence of weak solutions.

Some evidence suggests that bone health can be regulated by gut microbiota. To better understand this, we performed 16S ribosomal RNA sequencing to analyze the intestinal microbial diversity in primary osteoporosis (OP) patients, osteopenia (ON) patients and normal controls (NC). We observed an inverse correlation between the number of bacterial taxa and the value of bone mineral density. The diversity estimators in the OP and ON groups were increased compared with those in the NC group. Beta diversity analyses based on hierarchical clustering and principal coordinate analysis (PCoA) could discriminate the NC samples from OP and ON samples. Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria constituted the four dominant phyla in all samples. Proportion of Firmicutes was significantly higher and Bacteroidetes was significantly lower in OP samples than that in NC samples (p

Monitoring glycosylation of the mAbs have been emphasized and routinely characterized in biopharmaceutical industries because the carbohydrate components are closely related to the safety, efficacy, and consistency of the antibodies. In this study, the comprehensive glycan profiling of a biosimilar candidate of cetuximab was successfully characterized using Normal phase high-performance liquid chromatography (NP-HPLC) in combination with Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). The presence of minor N-linked glycans containing sialic acid lactone residues (NeuAcLac) was observed in the biosimilar for the first time, which could influence the quantitative analysis of sialylated glycans and interfere with quantification of neutral glycans when it was analyzed by high performance liquid chromatography fluorescence (HPLC-FL). To overcome this issue, mild alkali treatment was used to hydrolyze lactone of the sialic acid to their neutral formation, which had no impact on the analysis of other glycans before and after the treatment. As a result, the mild alkali treatment might be helpful to obtain quantitative glycan profiling of the mAbs drugs with enhanced accuracy and robustness.

In this short article, we study the blow-up properties of solutions to a parabolic problem with a gradient nonlinearity under homogeneous Dirichlet boundary conditions. By constructing an auxiliary function and by modifying the first order differential inequality technique introduced by Payne et al., we obtain a lower bound for the blow-up time of solutions in a bounded domain $\Omega\subset \mathbb{R}^n$ for any $n\geq3$. This article generalizes a result in [16].

The authors of this paper prove the existence and regularity results for the homogeneous Dirichlet boundary value problem to the equation - div(M(x)∇un)=f(x)/uα(x) with f∈Lm(Ω) (m⩾…1) and α(x)>0. The results show the dependence of the summability of f in some Lebesgue spaces and on the values of α(x).

In this article, we present the optimal control for the modified Swift-Hohenberg equation, under certain boundary conditions, and show the existence of an optimal solution.