Bioactivities and industrial standardization status of Ganoderma lucidum: A comprehensive review.

Ganoderma lucidum (GL) is a potent source of bioactive compounds with diverse nutritional and pharmacological benefits. Its popularity as a dietary supplement, herbal remedy, and wellness product is steadily on the rise. Furthermore, the standardized advancement of the GL industry has facilitated reliable sourcing of raw materials and quality control measures, enhancing its utilization and endorsement in the realms of nutritional science and pharmaceutical research. This article provides a comprehensive overview of the recent advancements in research pertaining to the bioactive components of GL, particularly polysaccharides (GLP) and triterpenes (GLTs) as well as highlights the latest findings regarding their beneficial effects on human diseases, including anticancer, antidiabetes, liver protection and other aspects (such as regulating gut microbiota, antioxidant, antimicrobial, antiinflammatory and immune regulation). Furthermore, we summarized the potential applications of GL in the food and pharmaceutical sectors, while also examining the current status of standardization throughout the entire industrial chain of GL, both domestically and internationally. These information offer an insight and guidance for the prospects of industrial development and the innovative advancement of GL within the global health industry.

GAPS: a geometric attention-based network for peptide binding site identification by the transfer learning approach.

Protein-peptide interactions (PPepIs) are vital to understanding cellular functions, which can facilitate the design of novel drugs. As an essential component in forming a PPepI, protein-peptide binding sites are the basis for understanding the mechanisms involved in PPepIs. Therefore, accurately identifying protein-peptide binding sites becomes a critical task. The traditional experimental methods for researching these binding sites are labor-intensive and time-consuming, and some computational tools have been invented to supplement it. However, these computational tools have limitations in generality or accuracy due to the need for ligand information, complex feature construction, or their reliance on modeling based on amino acid residues. To deal with the drawbacks of these computational algorithms, we describe a geometric attention-based network for peptide binding site identification (GAPS) in this work. The proposed model utilizes geometric feature engineering to construct atom representations and incorporates multiple attention mechanisms to update relevant biological features. In addition, the transfer learning strategy is implemented for leveraging the protein-protein binding sites information to enhance the protein-peptide binding sites recognition capability, taking into account the common structure and biological bias between proteins and peptides. Consequently, GAPS demonstrates the state-of-the-art performance and excellent robustness in this task. Moreover, our model exhibits exceptional performance across several extended experiments including predicting the apo protein-peptide, protein-cyclic peptide and the AlphaFold-predicted protein-peptide binding sites. These results confirm that the GAPS model is a powerful, versatile, stable method suitable for diverse binding site predictions.

PepExplainer: An explainable deep learning model for selection-based macrocyclic peptide bioactivity prediction and optimization.

Macrocyclic peptides possess unique features, making them highly promising as a drug modality. However, evaluating their bioactivity through wet lab experiments is generally resource-intensive and time-consuming. Despite advancements in artificial intelligence (AI) for bioactivity prediction, challenges remain due to limited data availability and the interpretability issues in deep learning models, often leading to less-than-ideal predictions. To address these challenges, we developed PepExplainer, an explainable graph neural network based on substructure mask explanation (SME). This model excels at deciphering amino acid substructures, translating macrocyclic peptides into detailed molecular graphs at the atomic level, and efficiently handling non-canonical amino acids and complex macrocyclic peptide structures. PepExplainer's effectiveness is enhanced by utilizing the correlation between peptide enrichment data from selection-based focused library and bioactivity data, and employing transfer learning to improve bioactivity predictions of macrocyclic peptides against IL-17C/IL-17 RE interaction. Additionally, PepExplainer underwent further validation for bioactivity prediction using an additional set of thirteen newly synthesized macrocyclic peptides. Moreover, it enabled the optimization of the IC50 of a macrocyclic peptide, reducing it from 15 nM to 5.6 nM based on the contribution score provided by PepExplainer. This achievement underscores PepExplainer's skill in deciphering complex molecular patterns, highlighting its potential to accelerate the discovery and optimization of macrocyclic peptides.

FUNDC1/PFKP-mediated mitophagy induced by KD025 ameliorates cartilage degeneration in osteoarthritis.

Osteoarthritis (OA) is the most common joint disease, but no disease-modifying drugs have been approved for OA treatment. Mitophagy participates in mitochondrial homeostasis regulation by selectively clearing dysfunctional mitochondria, which might contribute to cartilage degeneration in OA. Here, we provide evidence of impaired mitophagy in OA chondrocytes, which exacerbates chondrocyte degeneration. Among the several classic mitophagy-regulating pathways and receptors, we found that FUNDC1 plays a key role in preserving chondrocyte homeostasis by inducing mitophagy. FUNDC1 knockdown in vitro and knockout in vivo decreased mitophagy and exacerbated mitochondrial dysfunction, exacerbating chondrocyte degeneration and OA progression. FUNDC1 overexpression via intra-articular injection of adeno-associated virus alleviated cartilage degeneration in OA. Mechanistically, our study demonstrated that PFKP interacts with and dephosphorylates FUNDC1 to induce mitophagy in chondrocytes. Further analysis identified KD025 as a candidate drug for restoring chondrocyte mitophagy by increasing the FUNDC1-PFKP interaction and thus alleviating cartilage degeneration in mice with DMM-induced OA. Our study highlights the role of the FUNDC1-PFKP interaction in chondrocyte homeostasis via mitophagy induction and identifies KD025 as a promising agent for treating OA by increasing chondrocyte mitophagy.

Acetylcysteine and budesonide for the treatment of refractory Mycoplasma pneumoniae pneumonia in children: a clinical observation.

BACKGROUND: To examine the clinical impact of bronchoscope alveolar lavage (BAL) combination with budesonide, ambroxol + budesonide, or acetylcysteine + budesonide in the treatment of refractory Mycoplasma pneumoniae pneumonia (RMPP). METHODS: Eighty-two RMPP patients admitted to Pediatrics at The First People's Hospital of Zhengzhou were retrospectively evaluated between August 2016 and August 2019. All patients were administered BAL in addition to intravenous Azithromycin, expectoration, and nebulizer inhalation. The medications added to the BLA separated the patients into the Budesonide group, Ambroxol + budesonide group, and acetylcysteine + budesonide group. Analyzed were the variations in laboratory examination indices, improvement in lung imaging, overall effective rate, and adverse responses in the three groups. RESULTS: The laboratory test indices of patients in all three groups improved significantly relative to pre-treatment levels, and the results were statistically significant. After therapy, there were no significant differences between the three groups in terms of white blood cell (WBC), C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR). Serum lactate dehydrogenase (LDH) and serum ferritin (SF) varied significantly across the three groups (P < 0.05). In the acetylcysteine + budesonide group, the absorption rate of lung imaging lesions and clinical efficacy were superior to those of the other two groups. There were no significant differences between the three groups in the occurrence of adverse events (P > 0.05). CONCLUSIONS: BLA-coupled acetylcysteine + budesonide was superior to the other two groups in enhancing the effectiveness of RMPP in children, which might increase lung opacity absorption and minimize lung inflammation.

PepScaf: Harnessing Machine Learning with In Vitro Selection toward De Novo Macrocyclic Peptides against IL-17C/IL-17RE Interaction.

The combination of library-based screening and artificial intelligence (AI) has been accelerating the discovery and optimization of hit ligands. However, the potential of AI to assist in de novo macrocyclic peptide ligand discovery has yet to be fully explored. In this study, an integrated AI framework called PepScaf was developed to extract the critical scaffold relative to bioactivity based on a vast dataset from an initial in vitro selection campaign against a model protein target, interleukin-17C (IL-17C). Taking the generated scaffold, a focused macrocyclic peptide library was rationally constructed to target IL-17C, yielding over 20 potent peptides that effectively inhibited IL-17C/IL-17RE interaction. Notably, the top two peptides displayed exceptional potency with IC50 values of 1.4 nM. This approach presents a viable methodology for more efficient macrocyclic peptide discovery, offering potential time and cost savings. Additionally, this is also the first report regarding the discovery of macrocyclic peptides against IL-17C/IL-17RE interaction.

Plasmon Driven Nanocrystal Transformation by Aluminum Nano-Islands with an Alumina Layer.

The plasmonic photothermal effects of metal nanostructures have recently become a new priority of studies in the field of nano-optics. Controllable plasmonic nanostructures with a wide range of responses are crucial for effective photothermal effects and their applications. In this work, self-assembled aluminum nano-islands (Al NIs) with a thin alumina layer are designed as a plasmonic photothermal structure to achieve nanocrystal transformation via multi-wavelength excitation. The plasmonic photothermal effects can be controlled by the thickness of the Al2O3 and the intensity and wavelength of the laser illumination. In addition, Al NIs with an alumina layer have good photothermal conversion efficiency even in low temperature environments, and the efficiency will not decline significantly after storage in air for 3 months. Such an inexpensive Al/Al2O3 structure with a multi-wavelength response provides an efficient platform for rapid nanocrystal transformation and a potential application for the wide-band absorption of solar energy.

[Efficacy of noninvasive high-frequency oscillatory ventilation versus nasal intermittent positive pressure ventilation as post-extubation respiratory support in preterm infants: a Meta analysis]. / æ— åˆ›é«˜é¢‘æŒ¯è¡é€šæ°”ä¸Žç»é¼»é—´æ­‡æ­£åŽ‹é€šæ°”ä½œä¸ºæ—©äº§å„¿æ‹”ç®¡åŽå‘¼å¸æ”¯æŒç–—æ•ˆæ¯”è¾ƒçš„Meta分析.

OBJECTIVES: To systematically evaluate the efficacy and safety of noninvasive high-frequency oscillatory ventilation (NHFOV) versus nasal intermittent positive pressure ventilation (NIPPV) as post-extubation respiratory support in preterm infants. METHODS: China National Knowledge Infrastructure, Wanfang Data, Chinese Journal Full-text Database, China Biology Medicine disc, PubMed, Web of Science, and the Cochrane Library were searched for articles on NHFOV and NIPPV as post-extubation respiratory support in preterm infants published up to August 31, 2022. RevMan 5.4 software and Stata 17.0 software were used for a Meta analysis to compare related indices between the NHFOV and NIPPV groups, including reintubation rate within 72 hours after extubation, partial pressure of carbon dioxide (PCO2) at 6-24 hours after switch to noninvasive assisted ventilation, and the incidence rates of bronchopulmonary dysplasia (BPD), air leak, nasal damage, periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). RESULTS: A total of 9 randomized controlled trials were included. The Meta analysis showed that compared with the NIPPV group, the NHFOV group had significantly lower reintubation rate within 72 hours after extubation (RR=0.67, 95%CI: 0.52-0.88, P=0.003) and PCO2 at 6-24 hours after switch to noninvasive assisted ventilation (MD=-4.12, 95%CI: -6.12 to -2.13, P<0.001). There was no significant difference between the two groups in the incidence rates of complications such as BPD, air leak, nasal damage, PVL, IVH, and ROP (P>0.05). CONCLUSIONS: Compared with NIPPV, NHFOV can effectively remove CO2 and reduce the risk of reintubation, without increasing the incidence of complications such as BPD, air leak, nasal damage, PVL, and IVH, and therefore, it can be used as a sequential respiratory support mode for preterm infants after extubation.

G-CSF reduces loss of dopaminergic neurons by inhibiting TNF-α and IL-1ß in mouse model of Parkinson's disease.

PURPOSE OF THE STUDY: granulocyte-colony stimulating factor (G-CSF) is a hematopoietic growth factor existing in neutrophils, glial cells and neurons. Increasing researches discovered that G-CSF improved cell survival in neurodegenerative diseases by its anti-inflammatory effect. However, the effect of G-CSF in suppressing inflammation in Parkinson's disease (PD) remains unclear. Thus, the purpose of this study is to explored the anti-inflammatory effect of G-CSF in mouse model of PD. MATERIALS AND METHODS: G-CSF was administrated in the PD model induced by MPTP. Subsequently, the protein of tyrosine hydroxylase (TH), ionized calcium-binding adaptor molecule 1 (Iba-1) and the inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in the midbrain were examined. In addition, the phosphorylated mitogen-activated protein kinases (MAPK) including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK in the midbrain were investigated. RESULTS: Compared with the MPTP group, the protein of TH in the midbrain was increased, while the Iba-1 and the inflammatory factors were decreased. In addition, the expression of phosphorylated JNK (p-JNK) in the midbrain of the MPTP + G-CSF group was decreased, while the phosphorylated ERK (p-ERK) levels were elevated. CONCLUSIONS: These findings emphasize that G-CSF inhibited the degradation of DA neurons. The protective effect is associated with the reduction of the inflammatory factors caused by the inhibition of the microglial activation. Moreover, G-CSF may decrease the inflammatory factors through the decrease of P-JNK and the increase of P-ERK.

Cherry extract on post-exercise muscle damage / Extrato de cereja em danos musculares pós-exercício / El extracto de cereza daños musculares post ejercicio

ABSTRACT Introduction: Cherry extract has a high amount of anthocyanins and flavonoids containing antioxidant effects. Its high antioxidant characteristics have been shown to reduce markers of delayed muscle soreness (DOMS) and exercise-induced muscle damage (EIMD) to improve recovery after exercise. Objective: Verify the effects of the cherry extract on post-exercise muscle damage. Methods: Google scholar, Medline, and Scopus were systematically searched until February 2022. The Cochrane Collaboration tool was applied to determine the risks of bias. Results: The results showed that cherry extract administration did not have a decreasing impact on creatine kinase levels overall: (WMD = 12.85 IU. L-1, 95% CI: −35.94, 61.64; P = 0.606). Considerable heterogeneity was observed among the articles (Cochran's Q-test = 990.80, P = 0.000, I2 = 96.7 %). However, there is a significant reducing effect on pain sensation by the consumption of cherry extract (WMD = −6.105 mm; 95% CI: −11.193 −1.017; p = 0.019). Conclusion: Cherry extract consumption effectively reduced late-onset muscle pain among participants in the overall and subgroup analysis. Thus, the cherry extract may be a complementary alternative in recovery after exercise. Level of evidence II; Therapeutic studies - Manuscript review.

RESUMO Introdução: O extrato de cereja tem uma alta quantidade de antocianinas e flavonóides contendo efeitos antioxidantes. Suas altas características antioxidantes demonstraram reduzir os marcadores de dor muscular retardada (DOMS) e dano muscular induzido pelo exercício (EIMD) para melhorar a recuperação após o exercício. Objetivo: Verificar os efeitos do extrato de cereja nos danos musculares pós-exercício. Métodos: Google scholar, Medline e Scopus foram sistematicamente pesquisados até fevereiro de 2022. A ferramenta de colaboração da Cochrane foi aplicada para determinar os riscos de viés. Resultados: Os resultados mostraram que a administração do extrato de cereja não teve um impacto decrescente nos níveis de creatina quinase em geral: (WMD = 12,85 IU. L-1, 95% CI: −35,94, 61,64; P = 0,606). Uma heterogeneidade considerável foi observada entre os artigos (teste Q da Cochran = 990,80, P = 0,000, I2 = 96,7 %). Porém, há um efeito redutor significativo na sensação de dor pelo consumo de extrato de cereja (WMD = −6,105 mm; 95% CI: −11,193 −1,017; p = 0,019). Conclusão: O consumo de extrato de cereja foi efetivo na redução de dores musculares de início tardio entre os participantes, na análise geral e nos subgrupos. Assim, o extrato de cereja pode ser uma alternativa complementar na recuperação após os exercícios. Nível de evidência II; Estudos terapêuticos - Revisão de manuscritos.

RESUMEN Introducción: El extracto de cereza tiene una gran cantidad de antocianinas y flavonoides con efectos antioxidantes. Se ha demostrado que sus altas características antioxidantes reducen los marcadores de dolor muscular retardado (DOMS) y el daño muscular inducido por el ejercicio (EIMD) para mejorar la recuperación después del ejercicio. Objetivo: Verificar los efectos del extracto de cereza en el daño muscular posterior al ejercicio. Métodos: Se realizaron búsquedas sistemáticas en Google scholar, Medline y Scopus hasta febrero de 2022. Se aplicó la herramienta de colaboración Cochrane para determinar los riesgos de sesgo. Resultados: Los resultados mostraron que la administración de extracto de cereza no tuvo un impacto decreciente en los niveles de creatina quinasa en general: (WMD = 12,85 UI. L-1, IC del 95%: −35,94, 61,64; P = 0,606). Se observó una considerable heterogeneidad entre los artículos (prueba Q de Cochran = 990,80, P = 0,000, I2 = 96,7 %). Sin embargo, el consumo de extracto de cereza tiene un efecto significativo de reducción del dolor (WMD = −6,105 mm; IC del 95%: −11,193 −1,017; p = 0,019). Conclusión: El consumo de extracto de cereza fue eficaz para reducir el dolor muscular de aparición tardía entre los participantes en el análisis global y de subgrupos. Así, el extracto de cereza puede ser una alternativa complementaria en la recuperación después de los ejercicios. Nivel de evidencia II; Estudios terapéuticos - Revisión de manuscritos.

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.

B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma.

OBJECTIVE: chordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas. METHODS: we profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro. RESULTS: We found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion. CONCLUSIONS: Our results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.

The Combination of Adipose-derived Schwann-like Cells and Acellular Nerve Allografts Promotes Sciatic Nerve Regeneration and Repair through the JAK2/STAT3 Signaling Pathway in Rats.

Schwann cells (SCs) combined with acellular nerve allografts (ANAs) effectively promote the regeneration and repair of peripheral nerves, but the exact mechanism has not been fully elucidated. However, the disadvantages of SCs include their limited source and slow rate of expansion in vitro. Previous studies have found that adipose-derived stem cells have the ability to differentiate into Schwann-like cells. Therefore, we speculated that Schwann-like cells combined with ANAs could profoundly facilitate nerve regeneration and repair. The aim of the present study was to investigate the cellular and molecular mechanisms of regeneration and repair. In this study, tissue-engineered nerves were first constructed by adipose-derived Schwann-like cells and ANAs to bridge missing sciatic nerves. Then, the rats were randomly divided into five groups (n = 12 per group): a Control group; a Model group; an ADSC group; an SC-L group; and a DMEM group. Twelve weeks postsurgery, behavioral function tests and molecular biological techniques were used to evaluate the function of regenerated nerves and the relevant molecular mechanisms after sciatic nerve injury (SNI). The results showed that adipose-derived Schwann-like cells combined with ANAs markedly promoted sciatic nerve regeneration and repair. These findings also demonstrated that the expression of neurotrophic factors (NFs) was increased, and the expression of Janus activated kinase2 (JAK2)/P-JAK2, signal transducer and activator of transcription-3 (STAT3)/P-STAT3 was decreased in the spinal cord after SNI. Therefore, these results suggested that highly expressed NFs in the spinal cord could promote nerve regeneration and repair by inhibiting activation of the JAK2/STAT3 signaling pathway.

AK-968 efficiently inhibits proliferation and induces cell apoptosis in human multiple myeloma cells.

AK-968 is a small molecular weight compound. In this study, we evaluated its anti-tumor effects on human multiple myeloma (MM) cells. Our results demonstrated that AK-968 markedly inhibited proliferation of MM cell lines in a dose-and time-dependent manner. Additionally, our flow cytometry data showed that MM cell apoptosis was significantly induced by AK-968. As expected, caspase-3 cleavage and alternation of mitochondrial membrane potential (MMP) in the MM cells treated by AK-968 was detected or quantified by Western Blot or Flow cytometry technique, respectively. In conclusion, our results suggested that AK-968 may act as a potential drug to treat human multiple myeloma.

MiR-455-3p inhibits the degenerate process of chondrogenic differentiation through modification of DNA methylation.

The aim of this work was to determine whether miR-455-3p regulates DNA methylation during chondrogenic differentiation of hMSCs. The expression of miR-455-3p and de novo methyltransferase DNMT3A was assessed in micromass culture of hBMSCs, which induced chondrogenic differentiation in vitro, and in E16.5 mice in vivo. A luciferase reporter assay was used to confirm whether miR-455-3p directly targets DNMT3A by interaction with the 3'-UTR. Using an Illumina Infinium Methylation EPIC microarray, genome-wide DNA methylation of hBMSCs with or without overexpressed miR-455-3p was examined for 28 days during induced chondrogenic differentiation. Here, we showed that miR-455-3p was more expressed during the middle stage of hBMSC chondrogenic differentiation, and less expressed in the late stage. DNMT3A was less expressed in the middle stage and more expressed in the late stage, and was also more expressed in the palms of miR-455-3p deletion mice compared to those of wild-type mice. The luciferase reporter assay demonstrated that miR-455-3p directly targets DNMT3A 3'-UTR. miR-455-3p overexpression inhibits the degenerate process during chondrogenic differentiation, while deletion of miR-455-3p in mice accelerated cartilage degeneration. Genome-wide DNA methylation analysis showed miR-455-3p overexpression regulates DNA methylation of cartilage-specific genes. GO analysis revealed PI3K-Akt signaling pathway was most hypomethylated. Our data show that miR-455-3p can regulate hMSC chondrogenic differentiation by affecting DNA methylation. Overexpression of miR-455-3p and DNA methylation inhibitors can thus potentially be utilized to optimize chondrogenic differentiation.

Unique adjustable UC luminescence pattern and directional radiation of peculiar-shaped NaYF4: Yb3+/Er3+ microcrystal particle.

A new design of peculiar-shaped ß-NaYF4: 20% Yb3+/2% Er3+ hexagonal microcrystal (PSßHM) is proposed and its upconversion (UC) luminescence with adjustable color pattern is studied with near infrared excitation. Flower-like green UC luminescence emission pattern from blooming to withering process and intensive directional red emission are achieved by simply adjusting the focal point position of the excitation light. The mechanism that determines the unique UC luminescence phenomena are investigated systematically. The function of the internal light reflection and waveguide effect with annular microcavity is explored based on the structure characteristic of the hexagonal microplate. The current work may have great significant and potential applications in the development of optoelectronic device, color display, directional light and laser emission of microsystem.

[Effect of chondrogenesis related miR-4287 on expression of aggrecanase-1 in human chondrocytes].

Objective: To investigate the effect and mechanism of miR-4287, a chondrogenesis associated microRNA, regulated the expression of aggrecanase-1 (a disintegrin and metalloproteinase with thrombospondin motif 4, ADAMTS4) in human chondrocytes. Methods: First, the voluntarily donated normal and osteoarthritic knee articular cartilages were used to detect the expressions of miR-4287 and ADAMTS4 mRNA by real-time fluorescence quantitative PCR. Then, chondrocytes were isolated from knee articular cartilages. The effect of IL-1ß on the expression of miR-4287 and ADAMTS4 mRNA was validated by the first generation of osteoarthritic chondrocytes. To confirm the influence of IL-1ß signal pathways on the expression of miR-4287 and ADAMTS4 mRNA, osteoarthritic chondrocytes were pretreated with MAPK signal pathway inhibitor SP600125, NF-κB pathway inhibitor SN50, and finally stimulated with IL-1ß. Chondro cytes were transfected with miR-4287 mimics and mimics negative control, inhibitors and inhibitors negative control respectively to value the effect of miR-4287 on ADAMTS4 expression. Luciferase reporter assay was used to verify the direct interaction between miR-4287 and putative site in the 3-untranslated region (3'UTR) of ADAMTS4 mRNA. Results: Compared with normal knee articular cartilages, the miR-4287 expression was markedly diminished and conversely ADAMTS4 mRNA expression was raised in osteoarthritis cartilages ( P<0.05). Stimulation with IL-1ß led to a reduction in miR-4287 expression and upregulation in ADAMTS4 mRNA expression, showing significant difference when compared with the untreated groups ( P<0.05). Pretreatment with IL-1ß signal pathway inhibitors induced miR-4287 expression and attenuated ADAMTS4 mRNA expression in human chondrocytes, which were significantly different from that of unstimulated cells ( P<0.05). ADAMTS4 mRNA and protein were suppressed by transfection with miR-4287 mimics ( P<0.05) and elevated by transfection with miR-4287 inhibitors ( P<0.05). As luciferase reporter assay showed, overexpression miR-4287 failed to alter the luciferase activity of a reporter construct containing either wild or mutant 3'UTR of ADAMTS4 mRNA ( P>0.05). Conclusion: miR-4287, a chondrogenesis associated microRNA, may play an important role in cartilage degeneration. miRNA-4287 is able to regulate ADAMTS4 expression in human chondrocytes, but not by means of directly targeted the ADAMTS4 mRNA 3'UTR. The exact mechanisms need to be further addressed.

Progesterone treatment improves cognitive outcome following experimental traumatic brain injury in rats.

Progesterone (PROG) has recently been shown to have a neuroprotective effect and improve cognitive outcome in animal models of traumatic brain injury (TBI). However, the precise mechanisms remain unclear. This study was aimed to investigate the inhibitory effects of PROG on inflammation and apoptosis in the hippocampus after TBI and its influence on the cognitive outcome. In this study, the model of TBI was established by modified Feeney's weight-dropping method. The PROG was given in a dose of 16 mg/kg by intraperitoneal injection 1h post injury and subsequent injections subcutaneously at 6h and 12 h after TBI. Brain samples were extracted at 24 h after trauma. The expression of COX-2 and caspase-3 was measured by immunohistochemistry and western blot technique. The cognitive outcome was assessed by Morris water maze test (MWM). The results revealed that the expression of COX-2 and caspase-3 in TBI-PROG group was distinctly less than those of the TBI group (p < 0.05). In addition, the performance of Morris water maze showed that progesterone treatment exhibited shorter latencies, more platform crossings and more time swimming in the quadrant area in the TBI+PROG rats compared to the TBI rats. In conclusion, post-TBI PROG administration may attenuate inflammation and apoptosis in the hippocampus, and this may be one of the mechanisms by which PROG improves cognitive outcome following TBI.