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Brain tissue is considered to be biphasic, with approximately 80% liquid and 20% solid matrix, thus exhibiting viscoelasticity due to rearrangement of the solid matrix and poroelasticity due to fluid migration within the solid matrix. However, how to distinguish poroelastic and viscoelastic effects in brain tissue remains challenging. In this study, we proposed a method of unconfined compression-isometric hold to measure the force versus time relaxation curves of porcine brain tissue samples with systematically varied sample lengths. Upon scaling the measured relaxation force and relaxation time with different length-dependent physical quantities, we successfully distinguished the poroelasticity and viscoelasticity of the brain tissue. We demonstrated that during isometric hold, viscoelastic relaxation dominated the mechanical behavior of brain tissue in the short-time regime, while poroelastic relaxation dominated in the long-time regime. Furthermore, compared with poroelastic relaxation, viscoelastic relaxation was found to play a more dominant role in the mechanical response of porcine brain tissue. We then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue. Because of the draining of pore fluid, the Young's moduli in poroelastic relaxation were lower than those in viscoelastic relaxation; brain tissue changed from incompressible during viscoelastic relaxation to compressible during poroelastic relaxation, resulting in reduced Poisson ratios. This study provides new insights into the physical mechanisms underlying the roles of viscoelasticity and poroelasticity in brain tissue. STATEMENT OF SIGNIFICANCE: Although the poroviscoelastic model had been proposed to characterize brain tissue mechanical behavior, it is difficult to distinguish the poroelastic and viscoelastic behaviors of brain tissue. The study distinguished viscoelasticity and poroelasticity of brain tissue with time scales and then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue, which helps to accurate selection of constitutive models suitable for application in certain situations (e.g., pore-dominant and viscoelastic-dominant deformation).

Aim: Lower grade gliomas [LGGs; World Health Organization (WHO) grades 2 and 3], owing to the heterogeneity of their clinical behavior, present a therapeutic challenge to neurosurgeons. The aim of this study was to explore the N6-methyladenosine (m6A) modification landscape in the LGGs and to develop an m6A-related microRNA (miRNA) risk model to provide new perspectives for the treatment and prognostic assessment of LGGs. Methods: Messenger RNA (mRNA) and miRNA expression data of LGGs were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. An m6A-related miRNA risk model was constructed via least absolute shrinkage and selection operator (LASSO), univariate, and multivariate Cox regression analysis. Next, Kaplan-Meier analysis, principal-component analysis (PCA), functional enrichment analysis, immune infiltrate analysis, dynamic nomogram, and drug sensitivity prediction were used to evaluate this risk model. Results: Firstly, six m6A-related miRNAs with independent prognostic value were selected based on clinical information and used to construct a risk model. Subsequently, compared with low-risk group, LGGs in the high-risk group had a higher m6A writer and reader scores, but a lower eraser score. Moreover, LGGs in the high-risk group had a significantly worse clinical prognosis than those in the low-risk group. Simultaneously, this risk model outperformed other clinicopathological variables in the prognosis prediction of LGGs. Immune infiltrate analysis revealed that the proportion of M2 macrophages, regulatory T (Treg) cells, and the expression levels of exhausted immune response markers were significantly higher in the high-risk group than in the low-risk group. Finally, this study constructed an easy-to-use and free dynamic nomogram to help clinicians use this risk model to aid in diagnosis and prognosis assessment. Conclusions: This study developed a m6A-related risk model and uncovered two different m6A modification landscapes in LGGs. Moreover, this risk model may provide guidance and help in clinical prognosis assessment and immunotherapy response prediction for LGGs.

Background The endoscopic endonasal approach (EEA) and the endoscopic supraorbital keyhole approach (eSKA) provide minimally invasive access to tuberculum sellae (TS) tumors. Evaluation of the operating maneuverability is helpful for approach selection. Herein, we compared the two approaches and aimed to provide quantitative anatomic data for surgical decision-making in the management of TS lesions. Methods Fifteen dissections were performed on five silicone-injected cadaveric heads. The EEA and eSKA (both right and left) were performed on each head. Surgical freedom and working angles in the axial and sagittal planes were calculated using the stereotactic navigation system in the selected six targets: the midpoint of the leading edge of the sphenoid sinus (leSS), the midpoint of the edge of the dorsum sellae (eDS), the ipsilateral medial opticocarotid recess (imOCR), the contralateral medial opticocarotid recess (cmOCR), the ipsilateral lateral opticocarotid recess (ilOCR), and the contralateral lateral opticocarotid recess (clOCR). Results The surgical freedom at the ilOCR and the axial working angles at the leSS, ilOCR, and imOCR (imOCR with excessive manipulation of the optic apparatus) were greater in the eSKA. The EEA provided greater surgical freedom and/or working angles at most targets than eSKA (the surgical freedom at the imOCR, cmOCR, clOCR, and eDS; the axial working angles at the cmOCR and clOCR; and the sagittal working angles at the leSS, imOCR, cmOCR, clOCR, and eDS). Conclusion The EEA provides greater surgical freedom and working angles for paramedian lesions, whereas the eSKA provides better surgical maneuverability for lesions with lateral extension.

Objective Biochemical remission rates of endoscopic endonasal transsphenoidal surgery (EETS) and its associated predictive factors were evaluated in patients with somatotrophin pituitary adenomas. Methods The patients who underwent EETS in Jinling Hospital were identified between 2011 and 2020. The surgeons' experience, preoperative insulin-like growth factor 1 (IGF-1), basal growth hormone (GH) levels, nadir GH levels, and the tumor characteristics were analyzed for their relationships with endocrine outcomes. Total 98 patients were included for single factor analysis and regression analysis. They were divided into three groups according to the admission chronologic order. Results The overall remission rate of the patients was 57% (56/98) for all the patients over 10 years. In the single factor analysis, we found that the tumor size, cavernous invasion, and sellar invasion were valuable to predict the endocrine outcome after surgery. As for the suprasellar invasion, no significant difference was found between the noninvasive group and the invasive group. The preoperative IGF-1 level (p = 0.166), basal GH level (p = 0.001), and nadir GH level (p = 0.004) were also different between the remission group and the nonremission group in the single factor analysis. The logistic regression analysis indicated that the preoperative nadir GH (odds ratio = 0.930, 95% confidence interval = 0.891–0.972, p = 0.001) was a significant predictor for the endocrine outcomes after surgery. Conclusion The surgeons' experience is an important factor that can affect the patients' endocrine outcomes after surgery. The macroadenomas with lateral invasion are more difficult to cure. Patients with higher preoperative nadir GH levels are less likely to achieve remission.

Solder joints of electronic packaging devices are used as mechanical fixation and electrical interconnection between chips and circuit boards, which provides protection for the normal operation of electronic equipment. Therefore, real-time monitoring of the status of solder joints is essential for predictive maintenance of equipment. In this paper, we propose a digital twin based on semi-supervised learning for diagnosing faults in chip interconnection solder joints. In order to achieve maximum generalization of limited label information, the interdependence between sample labels with similar feature distributions is fully exploited by semi-supervised learning. Additionally, we use real-time monitoring data to update the learning model, and reveal the evolution of solder joint failure under different loads through diagnostic results of model. A dynamic model is formed by stimulated fault evolution characteristics into a solder joint failure model to form a diagnose fault dynamic model in a virtual space. Finally, we designed a thermal-vibration coupling experiment to verify the effectiveness of the digital twin-based solder joint failure diagnosis model. The results show that the digital twin maintains good consistency with the performance degradation process of the solder joint throughout its life cycle. Moreover, the diagnostic accuracy of the digital twin model can reach 85%, which proves that our method can monitor the service status of physical entities online, and intelligently predict the failure mode and life cycles under load conditions.

AIM: Cavernous sinus hemangiomas (CSHs) are hypervascular malformations and the surgical treatment is technically demanding. Although some articles have reported resection of CSHs using endoscopic endonasal transsphenoidal surgery (EETS), most of them were encountered for a lack of preoperative strategy guidance. Herein, we reported gross total resection (GTR) of intrasellar CSHs in two patients undergoing strategical EETS and compared EETS with frontotemporal craniotomy (FC) and stereotactic radiosurgery by literature review. MATERIAL AND METHODS: Two patients with CSHs who underwent EETS were reported. The literature review was conducted to exhaust studies that reported surgical treatment for CSHs. The tumor resection rate, and the postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were extracted. RESULTS: GTR was achieved with no postoperative complications in the two cases. Nine articles reported 14 cases undergoing EETS for CSHs and twenty-three articles reported 195 cases undergoing FC for CSHs. The GTR rates of EETS and FC were 57.14% (8/14) and 78.97% (154/195) respectively. The postoperative short-term and long-term newly-developed or deteriorative cranial-nerve function rates were 0% (0/7) and 0% (0/6) for the EETS group, and 57% (57/100) and 18.18% (18/99) for the FC group. According to the previous meta-analysis, stereotactic radiosurgery resulted in remarkable tumor shrinkage in 67.80% (40/59) of patients and partial shrinkage in 25.42% of patients. DISCUSSION: The results showed that the intrasellar type of CSHs could be removed safely by EETS without crossing the nerves in the CS.

TRIpartite motif (TRIM) proteins are important members of the Really Interesting New Gene-finger-containing E3 ubiquitin-conjugating enzyme and are involved in the progression of hepatocellular carcinoma (HCC). However, the diverse expression patterns of TRIMs and their roles in prognosis and immune infiltrates in HCC have yet to be analyzed.Combined with previous research, we used an Oncomine database and the Human Protein Atlas to compare TRIM family genes' transcriptional levels between tumor samples and normal liver tissues, as verified by the Gene Expression Profiling Interactive Analysis database. We investigated the patient survival data of TRIMs from the Kaplan-Meier plotter database. Clinicopathologic characteristics associations and potential diagnostic and prognostic values were validated with clinical and expressional data collected from the cancer genome atlas.We identified TRIM28, TRIM37, TRIM45, and TRIM59 as high-priority members of the TRIMs family that modulates HCC. Low expression of TRIM28 was associated with shorter overall survival (OS) than high expression (log-rank p = 0.009). The same trend was identified for TRIM37 (p = 0.001), TRIM45 (p = 0.013), and TRIM59 (p = 0.011). Multivariate analysis indicated that the level of TRIM37 was a significant independent prognostic factor for both OS (p = 0.043) and progression-free interval (p = 0.044). We performed expression and mutation analysis and functional pathways and tumor immune infiltration analysis of the changes in TRIM factors.These data suggested that TRIM28, TRIM37, TRIM45, and TRIM59 could serve as efficient prognostic biomarkers and therapeutic targets in HCC.

In the 5 years since the fourth edition of the WHO Classification of Tumors of the Central Nervous System (CNS) (revised) was released, the development of targeted sequencing and omics technology has helped researchers in the field of neuro-oncology to identify some new tumor types in clinical practice, as well as a series of genetic parameters related to tumor occurrence and development, poor prognosis, treatment response, etc. These findings not only provide basic knowledge for the classification of glioma, but also promote the progress of the treatment of gliomas. As a revolution in cancer treatment, immunotherapy has become a promising strategy since the pioneering discovery of lymphatics in the CNS. The advancement and clinical application of immunotherapy have strengthened the demand for accurate classification of glioma. In June 2021, the WHO and the International Agency for Research on Cancer (IARC) published the fifth edition of the WHO Classification of Tumors of the CNS. The fifth edition focuses on advancing the role of genetic parameters in the classification of glioma and divides glioma into more biologically and molecularly defined entities, with better natural history characteristics, and introduced new tumor types and subtypes, especially in the pediatric population. Most importantly, these updated classifications will enable clinicians to better assess the prognosis and formulate the optimal treatment of gliomas.

Tendon–bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC–EVs and the underlying mechanisms of their effects on promoting tendon–bone healing. At last, we discuss the present challenges and future research directions. Graphical Abstract

BackgroundWe previously introduced the one-and-a-half (1½) nostril endoscopic transsphenoidal approach (OETA) to reduce the damage to the nasal structures. Here, we reported the modified approach which is called the endoscopic 1½-transseptal approach (EOTA) for pituitary surgery by combining the OETA and the microscopic transseptal approach to simplify intranasal procedures and protect nasal mucosa. In EOTA, we removed the sellar lesions in a corridor that is composed of the right submucosal space and the anterior left ½ nasal cavity.MethodsWe introduced EOTA with a detailed technical description and preliminary clinical outcomes. A total of 128 patients who underwent EOTA for pituitary surgery from July 2018 to September 2020 were reviewed for evaluation of the safety and efficacy of this approach.ResultsEOTA had a high gross total resection (GTR) rate and a 1ow complication rate. GTR was achieved in 106 (82.8%) patients, with 81.4% for pituitary adenomas and 93.3% for other non-adenomatous lesions. Post-operative complications included 3 patients (2.3%) with postoperative cerebrospinal fluid leak, 3 patients (2.3%) with diabetes insipidus, 5 patients (3.9%) with anterior pituitary insufficiency and 2 patients (1.6%) with meningitis. In addition, EOTA simplified the intranasal procedures, which led to shortened operation time (67.8 minutes). The results of ASK nasal-12, the Lund-Kennedy score, and the odor identification test showed that patients who underwent EOTA recovered quickly after surgery and the nasal cavity returned to the preoperative condition both apparently and physiologically one month after surgery.ConclusionsEOTA is a simple, safe and effective approach for pituitary lesions, which provides not only a sufficient surgical corridor for 2-surgeon/4- or 3-hands technique but also minimally invasive access to the sellar region.

Injuries to the central nervous system (CNS) often lead to severe neurological dysfunction and even death. However, there are still no effective measures to improve functional recovery following CNS injuries. Optogenetics, an ideal method to modulate neural activity, has shown various advantages in controlling neural circuits, promoting neural remapping, and improving cell survival. In particular, the emerging optogenetics has exhibited promising therapeutic methods for CNS injuries. In this review, we introduced the light-sensitive proteins and light stimulation system which are important components of optogenetic technology in detail and summarized the development trends. Meanwhile, we constructed a comprehensive picture of the current application of optogenetics in CNS injuries and highlighted recent advances for the treatment and functional recovery of neurological deficits. Finally, we discussed the therapeutic challenges and prospective uses of optogenetics therapy by photostimulation/photoinhibition modalities that would be suitable for clinical applications.

Metagenomic next-generation sequencing (mNGS) is a new approach to identify the infecting organism in infectious diseases. Our aim was to evaluate the accuracy of mNGS in determining the etiology of spinal infection. In this retrospective study, patients who had a suspected spinal infection and underwent mNGS for diagnosis in our hospital were eligible for inclusion. Samples for mNGS, culture, and histopathological tests were collected surgically or with a CT-guided needle biopsy. Sensitivity and specificity were calculated for mNGS and culture test, using histopathological results as reference. A total of 31 mNGS tests in 30 cases were included. Twenty-six cases were classified as infected, and four cases were considered aseptic. mNGS achieved a specificity of 75.0% [95% confidence interval (CI), 21.9% to 98.7%], sensitivity was 70.3% (95% CI, 49.7% to 85.5%). mNGS was more sensitive than culture at 14.8% (95% CI, 4.9% to 34.6%, P

Synthetic hydrogels from polyisocyanides (PIC) are a type of novel thermoreversible biomaterials, which can covalently bind biomolecules such as adhesion peptides to provide a suitable extracellular matrix (ECM)-like microenvironment for different cells. Although we have demonstrated that PIC is suitable for three-dimensional (3D) culture of several cell types, it is unknown whether this hydrogel sustains the proliferation and passaging of cells originating from different germ layers. In the present study, we propose a 3D culture system for three representative cell sources: Schwann cells (ectoderm), hepatocytes (endoderm), and endothelial cells (mesoderm). Both Schwann cells and hepatocytes proliferated into multicellular spheroids and maintained their properties, regardless of the amount of cell-adhesive RGD motifs in long-term culture. Notably, Schwann cells grew into larger spheroids in RGD-free PIC than in PIC-RGD, while HL-7702 showed the opposite behavior. Endothelial cells (human umbilical vein endothelial cells, HUVECs) spread and formed an endothelial cell (EC) network only in PIC-RGD. Moreover, in a hepatocyte/HUVEC co-culture system, the characteristics of both cells were well kept for a long period in PIC-RGD. In all, our work highlights a simple ECM mimic that supports the growth and phenotype maintenance of cells from all germ layers in the long term. Our findings might contribute to research on biological development, organoid engineering, and in vitro drug screening.

Although bromocriptine (BRC) as first-line drug is recommended for treating patients with prolactinoma, a minority of patients with prolactinoma are resistance to BRC. Moreover, our previous study showed the difference in drug sensitivity in BRC-treated rat prolactinoma cells, MMQ cells are more resistant to BRC, and GH3 cells are more sensitive to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to further investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. CCK-8 kit was used to test cell growth. Cell cycle analysis and apoptosis were performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analyzed using the Affymetrix Gene-Chip array. Western blot was used to test protein expression. Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cells by inhibiting the AKT/GSK-3β signaling pathway. The same results were confirmed invivo study. Taken together, Cur sensitizes rat prolactinoma cells to BRC by activating the ERK/EGR1 and inhibiting the AKT/GSK-3β signaling pathway.

Background: Approximately 30–40% of growth hormone-secreting pituitary adenoma (GHPA) harbor somatic mutations in the GNAS (α subunit of the stimulatory G protein) gene. However, the latent functional role of the mutations and relative molecular mechanism in GHPA remain unknown. Methods: The GNAS gene mutations were detected in GHPAs using a standard PCR-sequencing procedure. The mutation-associated MEG3 expression was measured by RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Alterations in mRNA profiles in the MEG3-overexpressed cells were analyzed by RNA-seq. The cell invasion ability was measured using a Transwell assay, and the EMT-associated proteins were quantified by immunofluorescence and western blot. Finally, a tumor cell xenograft mouse model was applied to verify the effect of MEG3 on tumor growth and invasiveness. Results: The percentage of invasive tumors was significantly declined in GNAS-mutated GHPA tumors with the GNAS mutations compared to those tumors with the wild-type of GNAS. Consistently, the GH3 cell invasion capacity was decreased by expressing the mutant GNAS. MEG3 is uniquely expressed at high levels in GHPA harboring the mutated GNAS gene. Accordingly, the upregulation of MEG3 resulted in inhibiting cell invasion; and vice versa, the downregulation of MEG3 led to enhancing cell invasion. Mechanistically, the high level of MEG3 in mutated GNAS cells prevented the cell invasion via inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. Conclusion: The GNAS mutations inhibit the invasiveness of GHPA cells via inactivation of the MEG3/Wnt/β-catenin signaling pathway.

BackgroundBinostril endoscopic transsphenoidal approach (BETA) is the most used approach for sellar lesions nowadays, while its damage to the nasal structures may cause nasal discomfort and affect nasal functions including respiration and olfaction. With the purpose to improve the post-operative sinonasal quality of life (QoL), we introduced the one-and-a-half nostril endoscopic transsphenoidal approach (OETA) in 2016 which preserved more natural structures and registered a prospective randomized controlled trial (ChiCTR-IOR-16008222) to compare the two approaches regarding the surgical outcomes and complications.MethodsSixty patients with pituitary adenomas were recruited and randomly assigned to the OETA group and the BETA group between April 2016 and May 2017 in Jinling Hospital. The tumor resection rate, endocrinal and visual outcomes, and surgical complications between the OETA and BETA groups were analyzed. Besides, the questionnaire Anterior Skull Base Nasal Inventory-12 (ASK Nasal-12) was used to evaluate patients’ sinonasal QoL at seven time points (pre-operative; 2-weeks, 1-month, 3-months, 6-months, 12-months, and long-term post-operatively). The Sniffin’ Sticks were used to assess patients’ olfactory function objectively in a long term. Each patient was followed for at least 12 months post-operatively.ResultsThere was no significant difference in tumor resection rate, hormonal and visual outcomes, and surgical complications between the two groups. Regarding the ASK Nasal-12, patients in the OETA group complained less about dried nasal material at 2 weeks after surgery (P = 0.017). One month after surgery, the OETA group had better olfaction function (P = 0.019) compared with the BETA group. However, there was no significant difference in early and long-term postoperative sinonasal QoL between the two approaches according to the entire ASK Nasal-12 metric. The results of the Sniffin’ Sticks showed that the two groups had a similar olfactory performance at long-time follow-up.ConclusionIn this single tertiary center trial, the results showed that the OETA achieved the same surgical outcomes and post-operative sinonasal QoL as the BETA. Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=13852, identifier: ChiCTR-IOR-16008222

To date, research regarding the changes of the sulfur and nitrogen rates in Wuhan during the summer is limited. In this study, we analyzed the air quality in Wuhan, China, using water-soluble ion, gaseous precursor, and weather data. A Spearman correlation analysis was then performed to investigate the temporal changes in air quality characteristics and their driving factors to provide a reference for air pollution control in Wuhan. The results indicate that SO2 in the atmosphere at Wuhan undergoes secondary conversion and photo-oxidation, and the conversion degree of SO2 is higher than that of NO2. During the summers of 2016 and 2017, secondary inorganic atmospheric pollution was more severe than during other years. The fewest oxidation days occurred in summer 2020 (11 days), followed by the summers of 2017 and 2014 (25 and 27 days, respectively). During the study period, ion neutralization was the strongest in summer 2015 and the weakest in August 2020. The aerosols in Wuhan were mostly acidic and NH4+ was an important neutralizing component. The neutralization factors of all cations showed little change in 2015. K+, Mg2+, and Ca2+ level changes were the highest in 2017 and 2020. At low temperature, high humidity, and low wind speed conditions, SO2 and NO2 were more easily converted into SO42− and NO3−.

In this article, five different cell placement structures of a vertical inverter chain were designed in a commercial bulk FinFET technology to investigate the effect of cell placement on a single-event transient (SET) pulse. 3-D TCAD mixed-mode simulation indicated that the cell placement has a significant effect on SET pulsewidths. Heavy-ion experiments at Cyclotron in the China Institute of Modern Physics in Lanzhou also indicated that the effect of cell placement on the SET pulse is obvious. The experiment also indicated that the effect of cell placement on P-hit SET is larger than that on N-hit SET, and charge sharing in vertical was becoming as important as that in horizontal.

Osteoarthritis (OA) is a chronic degenerative joint disease characterized by deterioration of articular cartilage. Dual specificity phosphatase 5 (DUSP5), a member of the DUSP subfamily, is known to regulate cellular inflammation. Here, we studied the relationship between DUSP5 and OA by knockdown and overexpression DUSP5, respectively. Results from in vitro experiments demonstrated that the knockdown of DUSP5 increased interleukin-1β (IL-1β)-induced expression of inflammatory genes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), and matrix metalloproteinases (MMPs) in chondrocytes, whereas it decreased the expression of anti-inflammatory genes, such as tissue inhibitor of metalloproteinase 3 (TIMP3) and IL-10. Conversely, the overexpression of DUSP5 suppressed the IL-1β-induced expression of iNOS, COX-2, and MMPs, and upregulated the expression of TIMP3 and IL-10. Moreover, knockdown of DUSP5 enhanced the IL-1β-induced activation of NF-κB and ERK pathways, whereas its overexpression inhibited these pathways. DUSP5 overexpression prevented cartilage degeneration in a rat OA model, while its knockdown reversed that effect. Our findings reveal that DUSP5 suppresses IL-1β-induced chondrocyte inflammation by inhibiting the NF-κB and ERK signaling pathways and ameliorates OA.

BTB Domain and CNC Homolog 1 (Bach1) has been implicated in cancer progression, particularly in invasion, but little is unknown about its effect on glioma. Here, we confirmed that highly expressed Bach1 prominently promoted glioma invasion. Similar to the reported mechanisms in other tumors, Bach1 upregulation was also correlated with epithelial mesenchymal transition (EMT) in glioma cells. More importantly, proteomic analysis indicated that the main mechanism of Bach1 promoting invasion in glioma involved extracellular matrix (ECM). We further found thatBach1 upregulation was associated with the multiple mechanisms of ECM remodeling in glioma, including increasing the expression and deposition of ECM components, activating TGFBR2-smad2/3 signaling, promoting invadopodia formation and inducing the expression and secretion of MMP2. Meanwhile, Bach1 overexpression increased ferroptosis sensitivity in glioma cells. The ferroptosis inducer (sulfasalazine) obviously suppressed the gliomas with Bach1 upregulation in vitro and in vivo. Overall, Bach1 has a two-faced role in glioma. Highly expressed Bach1 promotes glioma invasion. Conversely, Bach1 upregulation is also a potential indicator of the sensitivity of ferroptosis inducers.

Background Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor/stem cells (CPSCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. Methods This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPSCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPSCs. After that, we used mitochondrial fusion promoter to induce fusion in CPSCs and then the chondrogenic markers were measured. Transmission electron microscopy (TEM) and confocal microscopy were used to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (Mfn2) in CPSC chondrogenic differentiation. In vivo, Mfn2 was over-expressed in sheets of rat CPSCs, which were then injected intra-articularly into the knees of rats. Results Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPSCs. The mass of mitochondria was higher in differentiated CPSC, and the fusion status was obvious relative to un-differentiated CPSC. Chondrogenesis of CPSCs was upregulated with the induction by mitochondrial fusion promoter. Mfn2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through NOTCH2 signal pathway. Conclusions Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPSCs. Mfn2 accelerates the chondrogenesis differentiation of CPSCs through Notch2. In vivo, Mfn2-OE in sheets of rCPSCs ameliorated OA in the rat model.

With the rapid development of human space explorations, whether human embryos can develop normally and reproduce beyond the planet of Earth has become a topic of concern for the scientific community and the general public. The long-term exposure to the space environmental factors poses potential hazards to embryonic development and reproductive health of mammals, and they are linked to the adverse effects of microgravity and cosmic radiation. In this review, we summarized the progress in the studies of the reproduction and development of mammals performed in spacecrafts, and with ground-based simulated microgravity and radiation by us and other groups. In particular, we discussed the study of the development of mouse preimplantation embryos under space conditions using the SJ-10 recoverable satellite which was recently published in National Science Review . The potential future studies of mammalian reproductive function and embryonic development in the space environment have also been briefly discussed and proposed. In summary, to accomplish human breeding in the outer space when other planets are colonized, further systematic evaluation of the effects of microgravity, cosmic radiation or other cosmic factors on reproductive and ontogenetic processes is required, while the protective methodology for reducing the reproductive hazards during spaceflight is also needed.

For the last two decades, endonasal approach has been regularly applied to treat skull base lesions. However, postoperative olfactory dysfunction remains an unsolved problem. This systematic review aimed to identify factors that might affect postoperative olfactory prognosis of patients undergoing endonasal surgery for resection of sellar/parasellar lesions. The literature search was conducted comprehensively to exhaust studies which focused on patients' olfaction with objective olfactory assessments after endonasal skull base surgery. We sought to characterize the potential factors that might affect postoperative olfactory outcomes. Nineteen articles met inclusion criteria. We found that (1) endoscopic surgery was beneficial to patients' olfactory prognosis than microscopic surgery (incidence of postoperative decreased olfactory function: 18.48% (39/211) for the endoscopic group and 36.88% (52/141) for the microscopic group, P < 0.01); meta-analysis for single rate, 20% (95% CI 9-30%) for the endoscopic group and 35% (95% CI 0-72%) for the microscopic group); (2) harvesting septal flaps was an unfavorable factor for olfactory recovery and the rescue flap technique should be preferred compared with the HB flap; (3) no evidence showed that resection of the middle turbinate was detrimental to recovery of olfaction. Patients undergoing endoscopic endonasal surgery may have better olfactory outcomes than those undergoing microscopic endonasal surgery for resection of sellar/parasellar lesions. Special attention should be paid when using septal flaps is planned and the rescue flap technique should be the preferred choice. After resecting the middle turbinate, patients' olfaction still has a great chance of returning to the baseline. More homogeneous and high-quality studies are needed for further assessment.

The development of life beyond planet Earth is a long-standing quest of the human race, but whether normal mammalian embryonic development can occur in space is still unclear. Here, we show unequivocally that preimplantation mouse embryos can develop in space, but the rate of blastocyst formation and blastocyst quality are compromised. Additionally, the cells in the embryo contain severe DNA damage, while the genome of the blastocysts developed in space is globally hypomethylated with a unique set of differentially methylated regions. The developmental defects, DNA damage and epigenetic abnormalities can be largely mimicked by the treatment with ground-based low-dose radiation. However, the exposure to simulated microgravity alone does not cause major disruptions of embryonic development, indicating that radiation is the main cause for the developmental defects. This work advances the understanding of embryonic development in space and reveals long-term extreme low-dose radiation as a hazardous factor for mammalian reproduction.

Osteoarthritis (OA) is a chronic degenerative joint disease, related to the overexpression of matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), inflammation, and chondrocyte apoptosis. Nesfatin-1 is an adipokine, which plays an important role in the development of OA, especially in obese people. In the present study, cartilage degradation and apoptosis observed in OA patients was evaluated. Furthermore, the anti-inflammatory and anti-apoptotic effects of nesfatin-1, and its underlying in vitro and in vivo mechanisms were investigated. The results showed that nesfatin-1 increased significantly the expression of collagen type II alpha 1 chain (Col2a1), and reduced the expression of MMPs, ADAMTS5, cyclooxygenase (COX)-2, caspase-3, nitric oxide (NO), inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), interleukin (IL)-6, and chondrocyte apoptosis rate, which may be induced by IL-1β in rat chondrocytes. Furthermore, nesfatin-1 treatment prevented cartilage degeneration in the rat OA model. It was found that nesfatin-1 suppressed the IL-1β-induced activation of NF-κB, the mitogen-activated protein kinase (MAPK), and the Bax/Bcl-2 signal pathway in chondrocytes. These results suggest that in vivo nesfatin-1 could play a protective role in the development of OA and can be potentially used for its treatment.

Diabetes mellitus (DM) is one of the prominent risk factors for pathological development and progression of tendinopathy. One feature of DM‐related changes in tendinopathy is accumulation of advanced glycation end products (AGEs) in affected tendons. Pioglitazone (Pio), a peroxisome proliferator‐activated receptor γ agonist, performs a protective effect against AGEs. The present study aimed to investigate the pathogenetic role of AGEs on tendon‐derived stem cells (TDSCs) and to determine the effect of Pio on AGEs‐induced TDSC dysfunctions. Results indicated that AGEs induced TDSC apoptosis as well as compensatory activation of autophagy. Pharmacologic activation/inhibition of autophagy leaded to alleviate/exacerbate apoptosis induced by AGEs. We further confirmed the effect of Pio on autophagy, which ameliorated apoptosis and abnormal calcification caused by AGEs both in vitro and in vivo. Thus, we suggest that Pio ameliorates the dysfunctions of TDSCs against AGEs by promoting autophagy, and we also reveal that Pio is a potential pharmacological choice for tendinopathy.

Microgravity has been shown to induces many changes in proliferation, differentiation and growth behavior of stem cells. Little is known about the effect of microgravity on hematopoietic differentiation of pluripotent stem cells (PSCs). In this study, we used the random position machine (RPM) to investigate whether simulated microgravity (SMG) allows the induction of hematopoietic stem/progenitor cell (HSPC) derived from human embryonic stem cells (hESCs) in vitro. The results showed that SMG facilitates hESCs differentiate to HSPC with more efficient induction of CD34+CD31+ hemogenic endothelium progenitors (HEPs) on day 4 and CD34+CD43+ HSPC on day 7, and these cells shows an increased generation of functional hematopoietic cells in colony-forming unit assay when compared with normal gravity (NG) conditions. Additionally, we found that SMG significantly increased the total number of cells on day 4 and day 7 which formed more 3D cell clusters. Transcriptome analysis of cells identified thousands of differentially expressed genes (DEGs) between NG and SMG. DEGs down-regulated were enriched in the axonogenesis, positive regulation of cell adhesion, cell adhesion molecule and axon guidance, while SMG resulted in the up-regulation of genes were functionally associated with DNA replication, cell cycle, PI3K-Akt signaling pathway and tumorigenesis. Interestingly, some key gene terms were enriched in SMG, like hypoxia and ECM receptor interaction. Moreover, HSPC obtained from SMG culture conditions had a robust ability of proliferation in vitro. The proliferated cells also had the ability to form erythroid, granulocyte and monocyte/macrophage colonies, and can be induced to generate macrophages and megakaryocytes. In summary, our data has shown a potent impact of microgravity on hematopoietic differentiation of hPSCs for the first time and reveals an underlying mechanism for the effect of SMG on hematopoiesis development.

Superconducting photodetection offers a wide spectral coverage ranging from the microwave to X-ray, and in the short wavelength range, single photon sensitivity can be achieved. However, in the longer wavelength infrared region, the system detection efficiency is low due to the lower internal quantum efficiency and weak optical absorption. Here, we utilized the superconducting metamatieral to enhance the light coupling efficiency and reach nearly perfect absorption at dual color infrared wavelengths. Dual color resonances arise from hybridization of local surface plasmon mode of the metamaterial structure and the Fabry-Perot-like cavity mode of metal (Nb)-dielectric (Si)-metamatieral (NbN) tri-layer structure. We demonstrated that, at the working temperature of 8 K slightly below T C ∼8.8 K, this infrared detector exhibits the peak responsivity of 1.2 × 106 V/W and 3.2 × 106 V/W at two resonant frequencies 36.6 THz and 104 THz, respectively. The peak responsivity is enhanced about ∼8 and ∼22 times, respectively, compared to that of non-resonant frequency (67 THz). Our work provides a way to harvest infrared light efficiently and hence improve the sensitivity of superconducting photodetectors in multispectral infrared range, which may find promising applications in thermal image and gas sensing etc.

Approximately 30–40% of growth hormone-secreting pituitary adenoma (GHPA) harbor somatic mutations in the GNAS (α subunit of the stimulatory G protein) gene. However, the latent functional role of the mutations and relative molecular mechanism in GHPA remain unknown. The GNAS gene mutations were detected in GHPAs using a standard PCR-sequencing procedure. The mutation-associated MEG3 expression was measured by RT-qPCR. MEG3 was manipulated in GH3 cells using a lentiviral expression system. Alterations in mRNA profiles in the MEG3-overexpressed cells were analyzed by RNA-seq. The cell invasion ability was measured using a Transwell assay, and the EMT-associated proteins were quantified by immunofluorescence and western blot. Finally, a tumor cell xenograft mouse model was applied to verify the effect of MEG3 on tumor growth and invasiveness. The percentage of invasive tumors was significantly declined in GNAS-mutated GHPA tumors with the GNAS mutations compared to those tumors with the wild-type of GNAS. Consistently, the GH3 cell invasion capacity was decreased by expressing the mutant GNAS. MEG3 is uniquely expressed at high levels in GHPA harboring the mutated GNAS gene. Accordingly, the upregulation of MEG3 resulted in inhibiting cell invasion; and vice versa, the downregulation of MEG3 led to enhancing cell invasion. Mechanistically, the high level of MEG3 in mutated GNAS cells prevented the cell invasion via inactivation of the Wnt/β-catenin signaling pathway, which was further validated in vivo. The GNAS mutations inhibit the invasiveness of GHPA cells via inactivation of the MEG3/Wnt/β-catenin signaling pathway.

Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in children. The aggressive behavior of ACP challenges the treatment for it. However, immunotherapy is rarely studied in ACP. In this research, we performed unsupervised cluster analysis on the 725 immune-related genes and arrays of 39 patients with ACP patients in GSE60815 and GSE94349 databases. Two novel immune subtypes were identified, namely immune resistance (IR) subtype and immunogenic (IG) subtype. Interestingly, we found that the ACPs with IG subtype (34.78%, 8/23) were more likely to respond to immunotherapy than the ACPs with IR subtype (6.25%, 1/16) via tumor immune dysfunction and exclusion (TIDE) method. Simultaneously, the enrichment analysis indicated that the differentially expressed genes (DEGs) (p < 0.01, FDR < 0.01) of the IG subtype were chiefly involved in inflammatory and immune responses. However, the DEGs of the IR subtype were mainly involved in RNA processing. Next, immune infiltration analysis revealed a higher proportion of M2 macrophage in the IG subtype than that in the IR subtype. Compared with the IR subtype, the expression levels of immune checkpoint molecules (PD1, PDL1, PDL2, TIM3, CTLA4, Galectin9, LAG3, and CD86) were significantly upregulated in the IG subtype. The ssGSEA results demonstrated that the biofunction of carcinogenesis in the IG subtype was significantly enriched, such as lymphocyte infiltration, mesenchymal phenotype, stemness maintenance, and tumorigenic cytokines, compared with the IR subtype. Finally, a WDR89 (the DEG between IG and IR subtype)-based nomogram model was constructed to predict the immune classification of ACPs with excellent performance. This predictive model provided a reliable classification assessment tool for clinicians and aids treatment decision-making in the clinic.

Glioblastoma multiforme (GBM) is a common and aggressive form of brain tumor. The NSingle-cell and bulk RNA-sequencing data were acquired from the GEO and TCGA databases, respectively. We used bioinformatics and statistical tools to analyze associations between mAt the single-cell level, m

Dopamine agonist (DA) is the first choice for the treatment of prolactinomas, and drug resistance is unavoidable during treatment due to the heterogeneity of tumors. The two prolactinoma cell lines (GH3 cells and MMQ cells) were found to have different sensitivity and responding modes to the cabergoline (CAB) and bromocriptine (BRC). In this research, we disclosed the capability of ACT001, a derivative of parthenolide analogs, to activate AMPK by increasing the intracellular reactive oxygen species (ROS) level and AMP/ATP ratio to reverse DA resistance through dual pathways in prolactinoma cells. The results indicated that ACT001 could reverse the CAB resistance in GH3 cells by inhibiting the mTOR signaling pathway, inducing cell death through autophagy, and reverse the BRC resistance in MMQ cells by activating the EGR1 signaling pathway, inducing cell death through apoptosis. Our results suggested that ACT001 is a promising therapeutic compound for treating DA-resistant prolactinomas.

IR-drop is a fundamental constraint by almost all integrated circuits (ICs) physical designs, and many iterations of timing engineer change order (ECO), IR-drop ECO, or other ECO are needed before design signoff. However, IR-drop analysis usually takes a long time and wastes so many resources. In this work, we develop a fast dynamic IR-drop predictor based on a machine learning technique, XGBoost, and the prediction method can be applied to vector-based and vectorless IR-drop analysis simultaneously. Correlation coefficient is often used to characterize the symmetry of prediction data and golden data, and our experiments show that the prediction correlation coefficient is more than 0.96 and the average error is no more than 1.3 mV for two industry designs, which are of 2.4 million and 3.7 million instances, respectively, and that the analysis is speeded up over 4.3 times compared with the IR-drop analysis by commercial tool, Redhawk.

Human pluripotent stem cells (PSCs) are known to differentiate into almost all the blood lineage cells in vitro and hold a great promise for studying human early hematopoietic development and have a huge potential in the treatment of hematological disorders. Although several methods of hematopoietic stem/progenitor cell (HSPC) differentiation have been developed, the HSPC yields achieved using these strategies are not yet available for clinical application. Recently, bioreactor-based devices and biochemical factors synergistically have been used to induce hematopoietic differentiation and showed a potential role in hematopoiesis. This chapter describes a protocol for using a random positioning machine bioreactor to culture human PSCs and the large-scale production of HPCs. Techniques for characterizing the differentiated cells and assessing the efficiency of hematopoietic differentiation in the bioreactor with immunostaining and flow cytometry are also presented.

Background: Osteoarthritis (OA) is a debilitating disease that inflicts intractable pain, a major problem that humanity faces, especially in aging populations. Stem cells have been used in the treatment of many chronic diseases, including OA. Cartilage progenitor cells (CPCs) are a type of stem cells with the ability to self- renew and differentiate. They hold a promising future for the understanding of the progression of OA and for its treatment. Previous studies have reported the relationship between mitochondrial dynamics and mesenchymal stem cell (MSC) proliferation, differentiation and aging. Mitochondrial dynamic and morphology change during stem cell differentiation. Methods: This study was performed to access the relationship between mitochondrial dynamics and chondrogenic differentiation of CPCs. Mitochondrial fusion and fission levels were measured during the chondrogenic differentiation process of CPCs. After that, we used mitochondrial fusion promoter to induce fusion in CPCs and then the chondrogenic markers were measured. Using Transmission Elecron Microscopy (TEM) and confocal microscopy to capture the mass and fusion status of mitochondria. Lentiviruses were used to detect the role of mitofusin 2 (MFN2) in CPC chondrogenic differentiation. In vivo, MNF2 was over-expressed in sheets of rCPCs, which were then injected intra-articularly into the knees of rats. Results: Mitochondrial fusion markers were upregulated during the chondrogenic induction process of CPCs. The mass of mitochondria was higher in differentiated CPC and the fusion status was obvious relative to un-differentiated CPC. Chondrogenesis of CPCs was upregulated with the induction by mitochondrial fusion promoter. MFN2 over-expression significantly increased chondrocyte-specific gene expression and reversed OA through Notch2 signal pathway.Conclusions: Our study demonstrated that the mitochondrial fusion promotes chondrogenesis differentiation of CPCs. MFN2 accelerates the chondrogenesis differentiation of CPCs through Notch2. In vivo, MNF2-OE in sheets of rCPCs ameliorated OA in the rat model.

Competitive endogenous RNAs (ceRNAs), as a newly identified regulating mechanism, have been demonstrated to play a crucial role in various human diseases. An increasing number of recent studies have revealed that circular RNAs (circRNAs) can function as ceRNAs. However, little is known about the role of circFAM160A2 in the pathological process of osteoarthritis (OA). This study is the first to examine the crucial role of the circFAM160A2-miR-505-3p-SIRT3 axis in osteoarthritis progression. miR-505-3p was selected from the interaction of a microRNA (miRNA) microarray comparing chondrocytes in OA and normal conditions and prediction results from TargetScan. RT-qPCR was performed to assess the expression of circFAM160A2, miR-505-3p , and SIRT3. A dual luciferase assay was used to validate the binding of circFAM160A2, miR-505-3p , and SIRT3. We used lentivirus and adeno-associated virus to establish in vitro and in vivo overexpression models. Western blotting, apoptosis assay, ROS detection assay, Safranin O staining , and CCK8 assay were employed to assess the role of circFAM160A2, miR-505-3p , and SIRT3. We found that miR-505-3p was upregulated and circFAM160A2 was downregulated in OA. While overexpression of circFAM160A2 decreased the production of extracellular matrix (ECM) degrading enzymes and ameliorated chondrocyte apoptosis and mitochondrial dysfunction, inhibition of miR-505-3p could reverse the protective effect of circFAM160A2 on the OA phenotype both in vitro and in vivo. In conclusion, circFAM160A2 can promote mitochondrial stabilization and apoptosis reduction in OA chondrocytes by targeting miR-505-3p and SIRT3, which might be a potential therapeutic target for OA therapy. Funding: This study was funded by National Natural Science Foundation of China (NO. 81401824, 81871793 and 81572173). Declaration of Interest: All authors have no conflicts of interest to declare. Ethical Approval: All animal experiments were approved by the Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine and carried out under the guidelines of the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.

Although bromocriptine (BRC) as first-line drugs are recommended for treating patients with prolactinoma, a minority of patients with prolactinoma resistance to BRC. Moreover, our previous study showed that the difference in drug sensitivity in BRC- treated rat prolactinoma cells, MMQ cells are more resistant to BRC, and GH3 cells are more sensitive to BRC. Curcumin (Cur) has been shown to inhibit proliferation of prolactinoma cell lines. The aim of this study is to further investigate whether Cur could enhance the growth-inhibitory effect of BRC resistance on prolactinoma cell lines and its possible mechanism. CCK-8 kit was used to test cell growth. Cell-cycle analysis and apoptosis was performed by flow cytometry. Electron microscopy was used to test autophagosome. The mRNA expression profiles were analysed using the Affymetrix Gene-Chip array. Western blotting was used to test protein expression. Our data showed that Cur enhanced the growth-inhibitory effect of BRC on GH3 and MMQ cell proliferation. BRC and Cur both induced cell apoptosis, and Cur could significantly increase the apoptosis of BRC on pituitary adenoma cells through the ERK/EGR1 signaling pathway. Moreover, Cur could enhance the autophagic cell death (ACD) of BRC on tumor cell by inhibiting the AKT/GSK3β signaling pathway. The same results were confirmed in vivo study. Taken together, Cur sensitizes rat pituitary adenoma cell to BRC by activating the ERK/EGR1 and inhibiting AKT/GSK3β signaling pathway.

Background For prolactinoma patients, dopamine agonists (DAs) are indicated as the first-line treatment and surgery is an adjunctive choice. However, with the development of surgical technique and equipment, the effect of surgery has improved. The aim of this study was to assess the efficacy and safety of surgery versus DAs in patients with different types of prolactinomas. Methods A systematic search of literature using Web of Science, PubMed, Cochrane Library, and Clinical Trial databases was conducted until July 12, 2019. Prolactinoma patients treated with DAs (bromocriptine or cabergoline) or surgery (microscopic or endoscopic surgery) were included. Outcomes included the biochemical cure rate, recurrence rate, prolactin level, improvement rates of symptoms, and incidence rates of complications. A random-effects model was used to pool the extracted data. Qualitative comparisons were conducted instead of quantitative comparison. Results DAs were better than surgery in terms of the biochemical cure rate (0.78 versus 0.66), but surgery had a much lower recurrence rate (0.19 versus 0.57). Full advantages were not demonstrated in improvement rates of symptoms and incidence rates of complications with both treatment options. In microprolactinoma patients, the biochemical cure rate of endoscopic surgery was equal to the average cure rate of DAs (0.86 versus 0.86) and it surpassed the biochemical cure rate of bromocriptine (0.86 versus 0.76). In macroprolactinoma patients, endoscopic surgery was slightly higher than bromocriptine (0.66 versus 0.64) in terms of the biochemical cure rate. Conclusion For patients with clear indications or contraindications for surgery, choosing surgery or DAs accordingly is unequivocal. However, for patients with clinical equipoise, such as surgery, especially endoscopic surgery, in microprolactinoma and macroprolactinoma patients, we suggest that neurosurgeons and endocrinologists conduct high-quality clinical trials to address the clinical equipoise quantitatively.

In most correlation filter target tracking algorithms, poor accuracy in the tracking process for complex field images of the target and scale change problems. To address these issues, this paper proposes an algorithm of adaptive multi-feature fusion with scale change correlation filtering tracking. Our algorithm is based on the rapid and simple Kernel-Correlated Filtering(K CF) tracker, and achieves the complementarity among image features by fusing multiple features of Color Nmae(CN), Histogram of Oriented Gradient(HOG) and Local Binary Pattern(LBP) with weights adjusted by visual evaluation functions. The proposed algorithm introduces scale pooling and bilinear interpolation to adjust the target template size. Experiments on the OTB-2015 dataset of 100 video frames are compared with several trackers, and the precision and success ratio of our algorithm on complex scene tracking problems are 17.7% and 32.1 % respectively compared to the based-KCF.

NR4A3 is a member of nuclear receptor subfamily 4, which is an important regulator of cellular function and inflammation. In this study, high expression of NR4A3 in human osteoarthritis (OA) cartilage was firstly observed. To explore the relationship between NR4A3 and OA, we used a lentivirus overexpression system to simulate its high expression and study its role in OA. Additionally, siRNA‐mediated knockdown of NR4A3 was used to confirm the findings of overexpression experiments. The results showed the stimulatory effect of IL‐1β on cartilage matrix‐degrading enzyme expression such as MMP‐3, 9, INOS and COX‐2 was enhanced in NR4A3‐overexpressed chondrocytes and decreased in NR4A3‐knockdown chondrocytes at both mRNA and protein levels, while IL‐1β‐induced chondrocyte‐specific gene (collagen 2 and SOX‐9) degradation was only regulated by NR4A3 at protein level. Furthermore, overexpression of NR4A3 would also enhance EBSS‐induced chondrocytes apoptosis, while knockdown of NR4A3 decreased apoptotic level after EBSS treatment. A pathway study indicated that IL‐1β‐induced NF‐κB activation was enhanced by NR4A3 overexpression and reduced by NR4A3 knockdown. We suggest that NR4A3 plays a pro‐inflammatory role in the development of OA, and we also speculate that NR4A3 mainly regulates cartilage matrix‐degrading gene expression under inflammatory conditions via the NF‐κB pathway.

Background: Several literatures reported that suturing dura was reliable in preventing cerebrospinal fluid (CSF) leak in transsphenoidal surgery. However, suturing and knotting is technically chall...

Platelet transfusion is one of the most reliable strategies to cure patients suffering from thrombocytopenia or platelet dysfunction. With the increasing demand for transfusion, however, there is an undersupply of donors to provide the platelet source. Thus, scientists have sought to design methods for deriving clinical-scale platelets ex vivo. Although there has been considerable success ex vivo in the generation of transformative platelets produced by human stem cells (SCs), the platelet yields achieved using these strategies have not been adequate for clinical application. In this review, we provide an overview of the developmental process of megakaryocytes and the production of platelets in vivo and ex vivo, recapitulate the key advances in the production of SC-derived platelets using several SC sources, and discuss some strategies that apply three-dimensional bioreactor devices and biochemical factors synergistically to improve the generation of large-scale platelets for use in future biomedical and clinical settings.

Anatomic skeletal features of the shoulder play important roles in anterior shoulder dislocation. However, studies on the effect of the humeral structure are few. This case-control study aimed to analyze the risk factors of anterior shoulder instability, including glenoid and humeral factors.Anterior shoulder instability was found in 64 of 10,035 individuals who underwent magnetic resonance imaging. Propensity score matching was used to select controls matched for age, sex, height, and weight. We analyzed the glenoid and humeral structural data using conditional logistic regression analysis and identified cutoff points using receiver operating characteristic curve analysis.Significant differences were found between the control and dislocation groups in the depth-to-width ratio (0.119 ± 0.034 vs. 0.105 ± 0.037, P = .021), height-to-width ratio (1.51 ± 0.13 vs. 1.67 ± 0.16, P .001), humeral head diameter-to-glenoid fossa diameter ratio (1.56 ± 0.11 vs. 1.64 ± 0.20, P .001), and humeral containing angle (67.3° ± 5.9° vs. 60.4° ± 5.9°, P .001). The humeral containing angle (odds ratio, 0.95; P = .024) and the glenoid height-to-width ratio (odds ratio, 7.88; P = .002), adjusted for the depth-to-width ratio and diameter ratio, were associated with anterior shoulder instability. The cutoff point for the humeral containing angle was 64° and for the height-to-width ratio was 1.60.This study revealed significant risk factors for shoulder instability in the Chinese Han population. The humeral containing angle and the glenoid height-to-width ratio were risk factors for anterior shoulder instability.

The treatment of hyperprolactinemia is based on the use of dopamine agonists, mainly bromocriptine (BRC) and cabergoline (CAB). They reduce tumour size effectively and restore gonadal function. However, there is a difference in drug sensitivity between CAB and BRC in patients with prolactinoma, although the underlying mechanisms are still unknown. Thus, we investigated whether there are differences in tumour sensitivity to CAB and BRC and their possible differential mechanisms in two prolactinoma cell lines. In our study, we found that GH3 cells are more sensitive to BRC and that MMQ cells are more sensitive to CAB. Moreover, BRC and CAB elicited cell death via different pathways; BRC induced prolactinoma cell death mainly through the apoptosis pathway, and CAB induced pituitary prolactinoma cell death mainly via the autophagic cell death pathway. Using gene microarray analysis, we found that BRC induces the apoptosis of prolactinoma cells through the ERK/EGR1 signalling pathway, whereas CAB induces autophagic death by inhibiting the AKT/mTOR signalling pathway. Our study showed the difference in tumour sensitivity and differential mechanisms in BRC- and CAB-treated prolactinoma cells, which provides a theoretical basis for the accurate treatment of prolactinoma.

Background The expression of follistatin‐like protein 1 (FSTL1) is closely associated with diseases of the musculoskeletal system. However, despite being a well characterized inflammatory mediator, the effects of FSTL1 on chondrocytes are not completely understood. In this study, we investigated the effects of FSTL1 on the expression of inflammatory and catabolic factors in rat chondrocytes. Methods Rat chondrocytes were treated directly with various concentrations of FSTL1 in vitro. The levels of matrix metalloproteinases (MMPs), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‐2, interleukin (IL)‐1β, tumour necrosis factor (TNF)‐α and IL‐6 were measured by polymerase chain reaction, ELISA and Western blotting. In addition, activation of the nuclear factor kappa B (NF‐κB) pathway was explored to identify potential regulatory mechanisms. Results Follistatin‐like protein 1 directly increased the expression of MMP‐1, MMP‐13, iNOS, COX‐2, IL‐1β, TNF‐α and IL‐6 at both gene and protein level in a dose‐dependent manner. Activation of NF‐ κB and phosphorylation of p65 were also promoted by FSTL1 stimulation. Conclusions Follistatin‐like protein 1 exerts pro‐inflammatory and catabolic effects on cultured chondrocytes via activation of the NF‐κB signalling pathway. FSTL1 may therefore be a target in the treatment of OA.