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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.

Open-door laminoplasty is widely used for patients with cervical spondylotic myelopathy (CSM). However, the loss of cervical lordosis (LCL) seems to be unavoidable in the long-term follow-up after surgery, which may affect the clinical outcomes. The risk factors for this complication are still unclear. In this study, patients who underwent open-door laminoplasty between April 2016 and June 2021 were enrolled. Cervical X-rays were obtained to measure the C2–7 Cobb angle, C2–7 sagittal vertical axis (SVA), T1 slope (T1S) and ranges of motion (ROM). Cervical computed tomography (CT) scans and magnetic resonance imaging (MRI) were collected to evaluate the cervical Hounsfield unit values (HU) and the relative cross-sectional area (RCSA) of paraspinal muscles, respectively. A total of 42 patients were included and the average follow-up period was 24.9 months. Among the patients, 24 cases (57.1%) had a LCL of more than 5° at a 1-year follow-up and were labeled as members of the LCL group. The follow-up JOA scores were significantly lower in the LCL group (13.9 ± 0.6 vs. 14.4 ± 0.8, p = 0.021) and the mean JOA recovery rate was negatively correlated with LCL (r = −0.409, p = 0.007). In addition, LCL was positively correlated to the preoperative T1S, flexion ROM, flexion/extension ROM and the RCSA of flexion/extension muscles, while it was negatively correlated to extension ROM and the HU value of cervical vertebrae. Furthermore, multiple linear regression showed that preoperative T1S, mean HU value of cervical vertebrae, flexion/extension ROM and the flexion/extension RCSA were independent risk factors for LCL. Spine surgeons should consider these parameters before performing open-door laminoplasty.

Volatile compounds in Chinese Zhizhonghe Wujiapi (WJP) medicinal liquor were extracted by solvent-assisted flavor evaporation extraction (SAFE) and stir bar sorptive extraction (SBSE), respectively, and identified by gas chromatography-mass spectrometry. Results showed that a total of 123 volatile compounds (i.e., 108 by SAFE, 50 by SBSE, and 34 by both) including esters, alcohols, acids, aldehydes, ketones, heterocycles, terpenes and terpenoids, alkenes, phenols, and other compounds were identified, and 67 of them were confirmed as aroma-active compounds by the application of the aroma extract dilution analysis coupled with gas chromatography-olfactometry. After making a simulated reconstitute by mixing 41 characterized aroma-active compounds (odor activity values ≥1) based on their concentrations, the aroma profile of the reconstitute showed good similarity to that of the original WJP liquor. Omission test further corroborated 34 key aroma-active compounds in the WJP liquor. The study of WJP liquor is expected to provide some insights into the characterization of special volatile components in traditional Chinese medicine liquors for the purpose of quality improvement and aroma optimization.

Salmonella , a major foodborne pathogen, causes severe gastrointestinal disease in people and animals worldwide. Plasmid-borne mcr-1 , which confers colistin resistance in Salmonella, has significant epidemiological interest for public health safety. Here, we report the first evidence of mcr-1 -mediated colistin resistance in one multidrug-resistant strain，namely 16062 in this study, from 355 Salmonella isolates collected for Jiaxing foodborne pathogen monitoring in Zhejiang Province in 2015-2019. In addition to colistin, 16062 displayed multidrug resistance to various antimicrobials (β-lactams, quinolone, sulfonamide, florfenicol, ampicillin, streptomycin, nalidixic acid, aminoglycoside, and trimethoprim-sulfamethox). The mcr-1 -carrying IncX4 plasmid (p16062-MCR) in this study shares a conserved structure with other mcr -IncX4 plasmids. We found that other antimicrobial-resistance genes ( aac(6')-Ib-cr , aadA1 , aadA2 , aph(3')-Ia , oqxA , oqxB , sul1 , and cmlA1 ) are located on p16062-cmlA, an atypical IncHI2 plasmid, in isolate 16062. This is the first identification of transferable colistin resistance in foodborne Salmonella isolate collected in Jiaxing city, the 5-year monitoring of which revealed limited dissemination. By determining the genetic features of the plasmid vehicle, the characteristics of transferable mcr genes circulating in isolates from Jiaxing are now clearer.

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

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.

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.

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.

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.

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.

Liver metastasis is a leading cause of death in patients with colorectal cancer (CRC). Increasing evidence demonstrates that competing endogenous RNA (ceRNA) networks play important roles in malignant cancers. The purpose of this study was to identify molecular markers and build a ceRNA network as a significant predictor of colorectal liver metastases (CRLM). By integrated bioinformatics analysis, we found that apolipoprotein C1 (APOC1) was upregulated in CRLM and associated with prognosis in patients with CRC and thereby established an APOC1-dependent ceRNA network. By survival analysis, expression analysis, and correlation analysis of each element in the ceRNA network, we identified that ZEB1-AS1, miR-335-5p and APOC1 regulated each other. We further experimentally confirmed that ZEB1-AS1 promoted a CRC progression via regulating the expression of miR-335-5p that controlled the expression of APOC1. Our findings indicate that the ZEB1-AS1-miR-335-5p-APOC1 ceRNA regulatory network is significantly valuable for better prognosis of patients with CRC and as a new therapeutic target for the treatment of CRLM.

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., Graphical abstract, This study reveals that circBANP promotes colorectal cancer 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 colorectal cancer.

Mesenchymal stem cells (MSCs) are promising candidates for tissue regeneration and disease treatment. However, long-term

Unbalanced metabolism of an extracellular matrix (ECM) in nucleus pulposus cells (NPCs) is widely acknowledged as the primary cause of intervertebral disc degeneration (IDD). Irisin, a novel myokine, is cleaved from fibronectin type III domain-containing 5 (FNDC5) and has recently been proven to regulate the metabolism of ECM. However, little is known about its potential on NPCs and the development of IDD. Therefore, this study sought to examine the protective effects and molecular mechanism of irisin on IDD in vivo and in vitro. Decreased expression levels of FNDC5 and anabolism markers (COL2A1 and ACAN) but increased levels of catabolism markers (ADAMTS4) were found in degenerative nucleus pulposus (NP) tissues. In a punctured-induced rat IDD model, irisin treatment was found to significantly slow the development of IDD, and in TNF-α-stimulated NPCs, irisin treatment partly reversed the disorder of ECM metabolism. In mechanism, RNA-seq results suggested that irisin treatment affected the Hippo signaling pathway. Further studies revealed that with irisin treatment, the phosphorylation levels of key factors (LATS and YAP) were downregulated, while the expression level of CTGF was upregulated. Moreover, CTGF knockdown partially eliminated the protective effects of irisin on the metabolism of ECM in NPCs, including inhibiting the anabolism and promoting the catabolism. Taken together, this study demonstrated that the expression levels of FNDC5 were decreased in degenerative NP tissues, while irisin treatment promoted the anabolism, inhibited the catabolism of the ECM in NPCs, and delayed the progression of IDD via LATS/YAP/CTGF signaling. These results shed light on the protective actions of irisin on NPCs, leading to the development of a novel therapeutic target for treating IDD.

BACKGROUND We report a case of Intracardiac, pulmonary, and intravenous cement embolism after cement-augmented pedicle screw instrumentation in treating spondylolisthesis underlying osteoporotic bone, which was successfully managed by conservative treatment. We describe the treatment and outcome of the patient, hoping to shed light on the management of bone cement embolism. CASE SUMMARY A 67-year-old female suffered from progressive low back pain and numbness in lower extremities for 30 years. She was diagnosed with L4 and L5 spondylolisthesis, spinal stenosis, and osteoporosis. The patient underwent spinal canal decompression, an interbody fusion of L4/5 and L5/S1, cement-augmented pedicle screw instrumentation in L4-L5 segments, and regular pedicle screw in S1 segments. Three days postoperatively, a sudden drop in oxygen saturation occurred. Computerized tomography scan confirmed Intracardiac, pulmonary, and intravenous embolism. The patient was treated conservatively by continuous low-flow oxygen inhalation, anti-coagulation, and antibiotic therapy for 1 mo and continued anticoagulation treatment for 6 mo. The patient showed no further symptoms in a 30-mo follow-up. CONCLUSION Intracardiac, pulmonary cement embolism after cement-augmented pedicle screw instrumentation is extremely rare. Careful clinical and radiographic evaluation is required in multiple sites of bone cement embolism. Conservative treatment may be a primary consideration in scattered emboli without life-threatening conditions, but a clinical decision should be made on an individualized basis.

The influences of Mn level (0–0.8 wt%) on the microstructure and mechanical properties of as-cast and T6 heat-treated low-silicon cast aluminium alloys were investigated. The results indicated that...

Graphical abstract, Highlights • N-glycoproteome of H. contortus discloses 291 proteins harboring 425 modification sites. • Glycoconjugates occur predominantly in the intestine and gonads of the adult parasitic worms. • Selected proteins of the C1 and M1 peptidase families are enriched in the parasite’s N-glycoproteome. • A repertoire of N-glycoproteins is associated with the nutrient acquisition and immune response. • Our systematic N-glycosylation profiling should facilitate research on vaccine development., 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.

Solar stills are considered an effective method to solve the scarcity of drinkable water. However, it is still missing a way to forecast its production. Herein, it is proposed that a convenient forecasting model which just needs to input the conventional weather forecasting data. The model is established by using machine learning methods of random forest and optimized by Bayesian algorithm. The required data to train the model are obtained from daily measurements lasting 9 months. To validate the accuracy model, the determination coefficients of two types of solar stills are calculated as 0.935 and 0.929, respectively, which are much higher than the value of both multiple linear regression (0.767) and the traditional models (0.829 and 0.847). Moreover, by applying the model, we predicted the freshwater production of four cities in China. The predicted production is approved to be reliable by a high value of correlation (0.868) between the predicted production and the solar insolation. With the help of the forecasting model, it would greatly promote the global application of solar stills.

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.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer of the digestive tract that has a high potential for metastasis and a poor prognosis. Girdin was first reported in 2005 as an actin-binding protein and was designated as Akt-phosphorylation enhancer (APE); thus, Girdin has been revealed to have an important role in regulating cancer development. There is additional evidence indicating that Girdin is associated with cell proliferation, migration, invasion and survival in certain cancers. However, the potential mechanisms involving Girdin and mobility in pancreatic cancer have not been elucidated. In the present study, it was revealed that Girdin was highly expressed in pancreatic cancer tissue and was associated with tumor grade. The present study, to the best of our knowledge, is the first aimed at investigating the unknown role of Girdin in PDAC metastasis. A short hairpin RNA for Girdin (sh-Girdin) was successfully constructed with recombinant adenoviral vectors to suppress the expression of Girdin in pancreatic cancer cell lines (PANC-1 and BXPC-3). The silencing efficiency of the Girdin shRNA was determined by RT-qPCR and western blot analysis, and decreased Girdin expression in the cytoplasm was revealed by immunofluorescence detection. Then, sulforhodamine B (SRB) and colony formation assays were used to confirm that the knockdown of Girdin inhibited proliferation in vitro, and Transwell assays were used to examine the influence of Girdin knockdown on cellular mobility. Animal experiments also confirmed that silencing the expression of Girdin in pancreatic cancer cells inhibited the growth and metastasis of pancreatic cancer in vivo. Transforming growth factor-β (TGF-β) is a common inducer of epithelial-mesenchymal transition (EMT) and can effectively induce EMT in PDAC. Notably, TGF-β-treated cells exhibited changes in the classic biological markers of EMT. The expression of E-cadherin, a marker of the epithelial phenotype, increased, and the expression of N-cadherin and vimentin, markers of the interstitial phenotype, decreased in response to sh-Girdin. According to these experiments, Girdin may affect pancreatic cancer progression and development by interacting with vimentin. Therefore, there is evidence indicating that Girdin could be designated as a prognostic biological indicator and a candidate therapeutic target for pancreatic cancer.

The excessive production of sulfur dioxide (SO2) and formaldehyde (FA) by organisms is closely associated with several diseases, including neurological disorders, respiratory disease, and genotoxicity. RNA plays a central role in the expression of genes. However, it is difficult for fluorescent probes to explore the intersecting correlation of SO2 and FA near the nucleolus regions due to the protective obstacle of the cell nucleus membrane. Herein, a unique fluorescent probe (DP) for reversible detection of the interaction of SO2 and FA in the nucleolus regions was constructed. In light of the outstanding attributes of DP, including a large fluorescence ratio variation, ultrafast detection of SO2, and excellent reversibility, it was successfully employed to track the variation of endogenous SO2 and FA in the cytoplasm and nucleolus regions of live cells. In addition, the DP probe could be applied to the imaging of endogenous SO2 and then recovered by FA in live mice.

SO2 and formaldehyde (FA) are important signal molecules in physiological and pathological processes. It is particularly urgent to seek a method that can monitor SO2 and FA in real-time to study their role in organisms. Herein, we designed and synthesized a ratiometric fluorescent probe NaP based on the FRET mechanism for the reversible detection of SO2 and FA. This probe possesses high sensitivity, good selectivity, excellent photostability, low cytotoxicity and an ultra-fast response to SO2 (within 5 s). Notably, the probe can be recovered efficiently by FA. In addition, the biological experiments showed that the novel probe NaP could reversibly image SO2 and FA in cells and mice.

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.

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.

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.

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 Conclusions Both anterior and posterior approaches are feasible for thoracic and lumbar tuberculosis. While for thoracic and lumbar tuberculosis patients with a single lesion limited in the anterior and middle columns of the spine without severe kyphosis, the anterior approach surgery may have greater advantages in kyphosis correction, bone fusion, wound healing, protection of the normal spine, and medical consumables and cost.