Selective Construction of C-S/S-N Bonds from N-Substituted O-Thiocarbamates and Indoles under Transition-Metal-Free Conditions.

A method for the selective construction of S-N/C(sp2)-S bonds using N-substituted O-thiocarbamates and indoles as substrates is reported. This protocol features good atom utilization, mild conditions, short reaction time, and wide substrate scope, which can provide a convenient path for the functionalization of indoles. In addition, the reaction could be scaled up on gram scale, showing potential application value in industry synthesis.

Investigation of lacrimal gland and extraocular muscle in thyroid eye disease patients with severe subjective dry eye disease: a multiparametric magnetic resonance imaging study.

PURPOSE: To analyze the radiological features of the lacrimal gland (LG) and extraocular muscle (EOM) in thyroid eye disease (TED) patients with severe subjective dry eye disease (DED) using magnetic resonance imaging (MRI) measurements. METHODS: In this cross-sectional study, mechanical ocular exposure, dry eye assessment and MRI data were collected. Patients were classified into non-severe subjective DED group with ocular surface disease index (OSDI) < 33 and severe subjective DED group with OSDI ≥ 33. Linear regression model was applied for comparing the OSDI < 33 and OSDI ≥ 33 group in TED patients. The predictive performance of MRI parameters and models was assessed by receiver operating characteristic curve (ROC) analysis. RESULTS: Consecutive 88 TED patients (176 eyes) were included in this study. In the OSDI < 33 group, 52 TED patients (104 eyes) with a mean clinical activity score (CAS) of 0.63 ± 0.75. In the OSDI ≥ 33 group, there are 36 TED patients (72 eyes), with a mean CAS of 1.50 ± 1.54. The age and sex of the patients were matched between the two groups. The OSDI ≥ 33 group had shorter tear break-up time, larger levator palpebrae superioris / superior rectus (LPS/SR), inferior rectus and lateral rectus, smaller LG, more inflammatory LPS/SR and inferior rectus than OSDI < 33 DED group (P < 0.05). In the linear regression analysis, compare to the OSDI < 33 DED group, the OSDI ≥ 33 group had larger medial rectus cross-sectional area (ß = 0.06, 95%CI: (0.02, 0.10), P = 0.008), larger inferior rectus cross-sectional area (ß = 0.06, 95%CI: (0.00, 0.12), P = 0.048), smaller LG cross-sectional area (ß = -0.14, 95%CI: (-0.25, -0.04), P = 0.008). In the ROC analysis, the area under curve of medial rectus, inferior rectus, LG, and combined model are 0.625, 0.640, 0.661 and 0.716, respectively. CONCLUSION: Multiparametric MRI parameters of the LG and EOM in TED patients with severe subjective DED were significantly altered. Novel models combining the cross-sectional area of LG, medial rectus and inferior rectus showed good predictive performance in TED patients with severe subjective DED.

Comparison of the clinical and radiographic outcomes of cortical bone trajectory and traditional trajectory pedicle screw fixation in transforaminal lumbar interbody fusion: a randomized controlled trial.

PURPOSE: To compare the clinical outcomes and radiographic outcomes of cortical bone trajectory (CBT) and traditional trajectory (TT) pedicle screw fixation in patients treated with single-level transforaminal lumbar interbody fusion (TLIF). METHODS: This trial included a total of 224 patients with lumbar spine disease who required single-level TLIF surgery. Patients were randomly assigned to the CBT and TT groups at a 1:1 ratio. Demographics and clinical and radiographic data were collected to evaluate the efficacy and safety of CBT and TT screw fixation in TLIF. RESULTS: The baseline characteristic data were similar between the CBT and TT groups. Back and leg pain for both the CBT and TT groups improved significantly from baseline to 24 months postoperatively. The CBT group experienced less pain than the TT group at one week postoperatively. The postoperative radiographic results showed that the accuracy of screw placement was significantly increased in the CBT group compared with the TT group (P < 0.05). The CBT group had a significantly lower rate of FJV than the TT group (P < 0.05). In addition, the rate of fusion and the rate of screw loosening were similar between the CBT and TT groups according to screw loosening criteria. CONCLUSION: This prospective, randomized controlled analysis suggests that clinical outcomes and radiographic characteristics, including fusion rates and caudal screw loosening rates, were comparable between CBT and TT screw fixation. Compared with the TT group, the CBT group showed advantages in the accuracy of screw placement and the FJV rate. CLINICAL TRIALS REGISTRATION: This trial has been registered at the US National Institutes of Health Clinical Trials Registry: NCT03105167.

Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).

Directed evolution rice genes with randomly multiplexed sgRNAs assembly of base editors.

CRISPR-based directed evolution is an effective breeding biotechnology to improve agronomic traits in plants. However, its gene diversification is still limited using individual single guide RNA. We described here a multiplexed orthogonal base editor (MoBE), and a randomly multiplexed sgRNAs assembly strategy to maximize gene diversification. MoBE could induce efficiently orthogonal ABE (<36.6%), CBE (<36.0%), and A&CBE (<37.6%) on different targets, while the sgRNA assembling strategy randomized base editing events on various targets. With respective 130 and 84 targets from each strand of the 34th exon of rice acetyl-coenzyme A carboxylase (OsACC), we observed the target-scaffold combination types up to 27 294 in randomly dual and randomly triple sgRNA libraries. We further performed directed evolution of OsACC using MoBE and randomly dual sgRNA libraries in rice, and obtained single or linked mutations of stronger herbicide resistance. These strategies are useful for in situ directed evolution of functional genes and may accelerate trait improvement in rice.

Magnetic resonance imaging parameters on lacrimal gland in thyroid eye disease: a systematic review and meta-analysis.

BACKGROUND: Thyroid eye disease is an extrathyroidal manifestation of Graves' disease and is associated with dry eye disease. This is the first systematic review and meta-analysis to evaluate the role of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease diagnosis, activity grading, and therapeutic responses prediction. METHODS: Up to 23 August, 2022, 504 studies from PubMed and Cochrane Library were analyzed. After removing duplicates and imposing selection criteria, nine eligible studies were included. Risk of bias assessment was done. Meta-analyses were performed using random-effect model if heterogeneity was significant. Otherwise, fixed-effect model was used. Main outcome measures include seven structural magnetic resonance imaging parameters (lacrimal gland herniation, maximum axial area, maximum coronal area, maximum axial length, maximum coronal length, maximum axial width, maximum coronal width), and three functional magnetic resonance imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-apparent diffusion coefficient or mean diffusivity, diffusion-weighted imaging-apparent diffusion coefficient). RESULTS: Thyroid eye disease showed larger maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width, diffusion tensor imaging-apparent diffusion coefficient/ mean diffusivity, and lower diffusion tensor imaging-fractional anisotropy than controls. Active thyroid eye disease showed larger lacrimal gland herniation, maximum coronal area, diffusion-weighted imaging-apparent diffusion coefficient than inactive. Lacrimal gland dimensional (maximum axial area, maximum coronal area, maximum axial length, maximum axial width, maximum coronal width) and functional parameters (diffusion tensor imaging-apparent diffusion coefficient, diffusion tensor imaging-apparent diffusion coefficient) could be used for diagnosing thyroid eye disease; lacrimal gland herniation, maximum coronal area, and diffusion-weighted imaging-apparent diffusion coefficient for differentiating active from inactive thyroid eye disease; diffusion tensor imaging parameters (diffusion tensor imaging-fractional anisotropy, diffusion tensor imaging-mean diffusivity) and lacrimal gland herniation for helping grading and therapeutic responses prediction respectively. CONCLUSIONS: Magnetic resonance imaging lacrimal gland parameters can detect active thyroid eye disease and differentiate thyroid eye disease from controls. Maximum coronal area is the most effective indicator for thyroid eye disease diagnosis and activity grading. There are inconclusive results showing whether structural or functional lacrimal gland parameters have diagnostic superiority. Future studies are warranted to determine the use of magnetic resonance imaging lacrimal gland parameters in thyroid eye disease.

Siglec15 Checkpoint Blockade for Simultaneous Immunochemotherapy and Osteolysis Inhibition in Lung Adenocarcinoma Spinal Metastasis via a Hollow Nanoplatform.

Low responsiveness to anti-programmed death-1/programmed death-ligand 1 (anti-PD-1/PD-L1) for solid tumors indicates the presence of other immunosuppressive pathways. Siglec15, a newly discovered immune checkpoint, has been reported to repress immune responses in the tumor microenvironment (TME) and regulate osteoclast differentiation. However, the role of Siglec15 in the treatment for bone metastasis remains unclear. Herein, Siglec15 shows significantly higher expression in lung adenocarcinoma spinal metastasis (LUAD-SM) than in para-cancerous spinal tissues and primary LUAD. Subsequently, a TME-responsive hollow MnO2 nanoplatform (H-M) loaded with Siglec15 siRNA and cisplatin (H-M@siS15/Cis) is developed, and the surface is modified with an aspartic acid octapeptide (Asp8 ), thus allowing H-M to target spinal metastasis. High drug-loading capacity, good biocompatibility, effective tumor accumulation, and efficient Siglec15 silencing are demonstrated. Furthermore, the nanoparticles could reverse immunosuppression caused by tumor cells and tumor-associated macrophages (TAMs) and inhibit osteoclast differentiation via Siglec15 downregulation in vitro. In a LUAD-SM mouse model, H-M@siS15/Cis-Asp8 exhibits superior therapeutic efficacy via synergetic immunochemotherapy and osteolysis inhibition. Taken together, this single nanoplatform reveals the therapeutic potential of the new immune checkpoint Siglec15 in LUAD-SM and provides a strategy to treat this disease.

Adolescent microglia stimulation produces long-lasting protection against chronic stress-induced behavioral abnormalities in adult male mice.

Our previous studies had reported that microglia activation one day before stress exposure prevented the behavioral abnormalities induced by chronic stress in adult mice, and a 10-day interval between microglia stimulation and stress exposure can abolish the prophylactic effect of LPS preinjection on the behavioral abnormalities induced by chronic stress, which, however, could be rescued by repeated LPS injection. This suggests that increased stimulation of microglia results in animals developing a strong ability to prevent deleterious stress stimuli. Because microglia in the adolescent brain exhibit flexible immunological plasticity, we hypothesize that a single low-dose LPS injection during adolescence may provide long-lasting protection against behavioral abnormalities induced by chronic stress in adult mice. As expected, our results showed that a single injection of LPS (100 µg/kg) at post-natal day 28 (PND 28) prevented the development of abnormal behaviors and shifted neuroinflammatory responses toward an anti-inflammatory phenotype in adult mice treated with CSDS at their different stages of the age (PND 56, 140, and 252). Moreover, pretreatment with minocycline or PLX3397 to inhibit microglial activation abolished the prophylactic effect of LPS preinjection after PND 28 on behavioral abnormalities and neuroinflammatory responses induced by CSDS in adult mice at their different stages of the age, PND 56, 140, and 252. These results indicate that stimulation of microglia in adolescence may confer long-lasting protection against neuroinflammatory responses and behavioral abnormalities induced by chronic stress in adult mice. This may offer the potential for the development of a "vaccine-like strategy" to prevent mental disorders.

ERK1/2-dependent BDNF synthesis and signaling is required for the antidepressant effect of microglia stimulation.

Depressed mice have lower numbers of microglia in the dentate gyrus (DG). Reversal of this decline by a single low dose of lipopolysaccharide (LPS) may have antidepressant effects, but there is little information on the molecular mechanisms underlying this effect. It is known that impairment of brain-derived neurotrophic factor (BDNF) signaling is involved in the development of depression. Here, we used a combination of neutralizing antibodies, mutant mice, and pharmacological approaches to test the role of BDNF-tyrosine kinase receptor B (TrkB) signaling in the DG in the effect of microglial stimulation. Our results suggest that inhibition of BDNF signaling by infusion of an anti-BDNF antibody, the BDNF receptor antagonist K252a, or knock-in of the mutant BDNF Val68Met allele abolished the antidepressant effect of LPS in chronically stressed mice. Increased BDNF synthesis in DG, mediated by extracellular signal-regulated kinase1/2 (ERK1/2) signaling but not protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling, was essential for the antidepressant effect of microglial stimulation. These results suggest that increased BDNF synthesis through activation of ERK1/2 caused by a single LPS injection and subsequent TrkB signaling are required for the antidepressant effect of hippocampal microglial stimulation.

Maslinic acid prevents IL-1ß-induced inflammatory response in osteoarthritis via PI3K/AKT/NF-κB pathways.

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin-1ß (IL-1ß) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL-1ß-induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL-6, inducible nitric oxide synthase, cyclooxygenase-2, and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti-inflammatory effect by inactivating the PI3K/AKT/NF-κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.

The level and prevalence of depression and anxiety among patients with different subtypes of irritable bowel syndrome: a network meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional bowel disorder. However, the difference of depression and anxiety comorbidities among different IBS subtypes is still not well evaluated. This study aims to investigate the difference in the level and prevalence of depression and anxiety among healthy controls and patients with different subtypes of IBS. METHODS: PubMed, EMBASE and the Cochrane library were searched systematically until August 17, 2020. Studies that investigated depression and/or anxiety levels or prevalence among different IBS-subtype patients measured at baseline or the same point were included. Network meta-analysis was conducted to analyze standardized mean difference (SMD) of anxiety and depression levels, and single arm meta-analysis was performed for prevalence of anxiety and depression among different IBS subtypes. RESULTS: Eighteen studies involving 7095 participants were included. Network meta-analyses results showed healthy controls had a lower level of depression than IBS with mixed symptoms of constipation and diarrhea (IBS-M) [SMD = - 1.57; 95% confidence interval (CI) - 2.21, - 0.92], IBS with constipation (IBS-C) (SMD = - 1.53; 95% CI - 2.13, - 0.93) and IBS with diarrhea (IBS-D)(SMD = - 1.41; 95% CI - 1.97, - 0.85), while no significant difference was found between IBS unclassified (IBS-U) and healthy controls (SMD = - 0.58; 95% CI - 2.15, 1.00). There was also no significant difference in the level of depression among different IBS subtypes patients. The results of anxiety were similar to depression. Ranking probability showed that IBS-M was associated with the highest level of depression and anxiety symptoms, followed by IBS-C/IBS-D and IBS-U. Single-arm meta-analysis showed IBS-C had the highest prevalence of depression (38%) and anxiety (40%), followed by IBS-D, IBS-M and IBS-U. CONCLUSION: The results indicated that IBS-M was more likely to be associated with a higher level of depression and anxiety, and the prevalence of depression and anxiety in IBS-C was highest. The psychological screening and appropriate psychotherapy are needed for patients with IBS-C, IBS-D and IBS-M instead of IBS-U.

Worse Response to Ursodeoxycholic Acid in Primary Biliary Cholangitis Patients with Autoimmune Hepatitis Features.

BACKGROUND: There is limited evidence on the treatment response of primary biliary cholangitis (PBC) with autoimmune hepatitis (AIH) features but not meet the criteria of PBC-AIH syndromes. The aim of this study was to elucidate the clinical characteristics of PBC patients with features of AIH. METHODS: We included patients with diagnostic criteria of PBC. All patients were treated with ursodeoxycholic acid (UDCA) and without immunosuppressive agents for >1 year. The biochemical response was evaluated at 1 year after the treatment of UDCA. RESULTS: Among 432 patients with PBC, 166 (38.4%) patients did not achieve biochemical response within 1 year of UDCA treatment. Nonresponders had a lower albumin level and higher immunoglobulin G, alanine transaminase (ALT), alanine aminotransferase (AST), alkaline phosphatase, glutamyl transpeptidase and total bilirubin levels (p < 0.05). The response rates were significantly lower in patients with elevated level of IgG or ALT or AST. Moreover, the higher the IgG or AST level was, the lower the response rate was in patients with PBC, regardless of cirrhosis. For patients with cirrhosis, there was no differences among patients with different levels of ALT. Patients in the PBC with AIH features group had a significant lower response rate than patients in the PBC-only group. Among the 139 patients who underwent liver biopsy, 54 were nonresponsive to UDCA and 48 (88.9%) shown mild interface hepatitis. CONCLUSION: In conclusion, PBC patients with AIH features had a worse response to UDCA therapy.

Procyanidin B3 alleviates intervertebral disc degeneration via interaction with the TLR4/MD-2 complex.

As a chronic musculoskeletal degeneration disease, intervertebral disc degeneration (IVDD) has been identified as a crucial cause for low back pain. This condition has a prevalence of 80% among adults without effective preventative therapy. Procyanidin B3 (Pro-B3) is a procyanidin dimer, which is widely present in the human diet and has multiple functions, such as preventing inflammation. But the inhibiting effect of Pro-B3 in IVDD development is still no known. Thus, our study aimed to demonstrate the therapeutical effect of Pro-B3 in IVDD and explain the underlying mechanism. In vitro studies, human nucleus pulposus (NP) cells were isolated and exposed in lipopolysaccharide (LPS) to simulate IVDD development. Pro-B3 pre-treatment inhibited LPS-induced production of inflammation correlated factors such as tumour necrosis factor α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and Nitric oxide (NO). On the other hand, LPS-medicated extracellular matrix (ECM) breakdown was blocked in Pro-B3 treated NP cells. Additionally, Pro-B3 treatment blocked the activation of NF-κB/toll-like receptor 4 pathway in LPS-exposed NP cells. Mechanistically, Pro-B3 could occupy MD-2's hydrophobic pocket exhibiting high affinity for LPS to intervene LPS/TLR4/MD-2 complex formation. In vivo, Pro-B3 treatment prevented the loss of gelatin NP cells and structural damage of annulus fibrosus in rat IVDD model. In brief, Pro-B3 is considered to be a treatment agent for IVDD.

Temporal discrepancy of airborne total bacteria and pathogenic bacteria between day and night.

As the most abundant microbes in the atmosphere, airborne bacteria are closely involved in affecting human health, regional climate and ecological balance. The mobility of airborne microorganisms makes it necessary to study the community dynamic in short cycle. Nevertheless, it remains obscure how the airborne bacteria especially the pathogenic bacteria vary on the small time scale of day and night. To investigate the nycterohemeral discrepancy of airborne total bacteria and pathogenic bacteria, PM2.5 samples were collected in Hangzhou between day and night. Microbial taxonomic information was obtained through 16S rRNA gene sequencing and "human pathogens database" screening. Further analyses based on Multiple Regression Matrices (MRM) approach and Concentration Weighted Trajectory (CWT) model were conducted to elucidate the effect of local environmental factors and long-range transport. The community composition of total bacteria tended to be similar in the daytime while pathogenic bacteria turned out to be homogeneous in the nighttime. To be vigilant, the diversity of airborne pathogenic bacteria echoed the frequency of anthropogenic activities with the pathogen inhalation rate roughly at 428 copies/h and 235 copies/h respectively in daytime and nighttime. The nycterohemeral discrepancy of total bacteria was principally driven by the filtering of environmental factors, i.e., CO and NO2, indicating that anthropogenic activities brought about the homogeneity. Airborne pathogenic bacteria coupled with the strong resistances of environmental filtering stood out from their non-pathogenic counterpart, which enabled the long-range transport. Indeed, the nycterohemeral discrepancy of pathogenic bacteria was shaped by the transport of air masses. This research filled the gaps in temporal variance of airborne microorganisms on the small time scale of day and night, providing crucial foundation for precisely predicting ecological and health effects of bioaerosols.

The protective effect of sinapic acid in osteoarthritis: In vitro and in vivo studies.

The anti-inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA-pretreated human chondrocytes showed lower levels of interleukin (IL)-1ß-induced IL-6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor-α (TNF-α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)-5. Furthermore, activation of nuclear factor κB (NF-κB), which was induced by IL-1ß, was also inhibited by SA through the pathway of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.

Inhibition of PI3K/Akt/NF-κB signaling with leonurine for ameliorating the progression of osteoarthritis: In vitro and in vivo studies.

Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant Herba Leonuri, has been shown associated with potent anti-inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin-1 beta (IL-1ß) induced over-production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose-dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL-1ß induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL-1ß induced activation of the PI3K/Akt/NF-κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.

The Protective Effect of Ligustilide in Osteoarthritis: An in Vitro and in Vivo Study.

BACKGROUND/AIMS: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. RESULTS: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/ß and suppressed the IL-1ß-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1ß-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. CONCLUSION: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1ß-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.

Association of osteoarthritis and circulating adiponectin levels: a systematic review and meta-analysis.

BACKGROUND: The objective of this study was to perform a meta-analysis to investigate the specific relationship between the expression level of circulating adiponectin and osteoarthritis (OA). METHOD: Multiple databases were searched to estimate the high quality of studies relevant to adiponectin and OA. We extracted the data from the eligible studies and included them in the meta-analysis using a random effects model. Subgroup analysis and meta-regression were further performed to explore the potential sources of heterogeneity. RESULTS: Ten articles consisting of thirteen case-control studies that contained a combined total of 1255 subjects. Our results revealed that the OA patients displayed higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11-0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians (P = 0.037). Moreover, the meta-regression analysis suggested that the sample size (P = 0.03) and nationality (p = 0.01) could account for a part of heterogeneity in our study. CONCLUSION: Taken together, the current study indicated that the adiponectin expression levels were higher in the OA patients than in the healthy controls and might be associated with OA prevalence.

Comparison of combined anterior-posterior approach versus posterior-only approach in neuromuscular scoliosis: a systematic review and meta-analysis.

PURPOSE: Neuromuscular scoliosis (NS) is a complicated spinal disorder, and it could be treated through posterior-only approach (POA) or combined anterior-posterior approach (APA), which one is better and how to choose the surgical tactic is still in controversy. So comparing POA with APA parameters in the treatment of NS is meaningful. METHODS: Database of PubMed, Embase and Cochrane Library was systematically searched, and the studies, which focus on the comparisons of POA and APA in the treatment of NS, were included. The meta-analysis was performed by RevMan 5.3. RESULTS: Seven retrospective studies with 602 patients were included in meta-analysis. In previous analysis, statistically significant differences were observed in the major parameters between APA and POA. However, the results of subgroup meta-analysis, which focused on the correction angle and loss angle to eliminate the influence of different preoperative angles, were tend to no difference between two groups, except loss angle of scoliosis (MD, 6.4; 95% CI - 0.19 to 13) and correction angle of pelvic obliquity (MD, - 3.44; 95% CI - 6.71 to - 0.17). CONCLUSIONS: Our meta-analysis suggested that POA was similar to APA in the correction of scoliosis in coronal and sagittal planes. However, APA had advantages in the correction of pelvic obliquity and decreasing the loss of angle between postoperation and follow-up in main scoliosis, whereas POA had advantages in operative time, blood loss, duration of hospital stay and complications. LEVEL OF EVIDENCE: Level II. These slides can be retrieved under Electronic Supplementary Material.

Chromophore-Based Luminescent Metal-Organic Frameworks as Lighting Phosphors.

Energy-efficient solid-state-lighting (SSL) technologies are rapidly developing, but the lack of stable, high-performance rare-earth free phosphors may impede the growth of the SSL market. One possible alternative is organic phosphor materials, but these can suffer from lower quantum yields and thermal instability compared to rare-earth phosphors. However, if luminescent organic chromophores can be built into a rigid metal-organic framework, their quantum yields and thermal stability can be greatly improved. This Forum Article discusses the design of a group of such chromophore-based luminescent metal-organic frameworks with exceptionally high performance and rational control of the important parameters that influence their emission properties, including electronic structures of chromophore, coligands, metal ions, and guest molecules.