ScRNA-seq reveals the spatiotemporal distribution of camptothecin pathway and transposon activity in Camptotheca acuminata shoot apexes and leaves.

Camptotheca acuminata Decne., a significant natural source of the anticancer drug camptothecin (CPT), synthesizes CPT through the monoterpene indole alkaloid (MIA) pathway. In this study, we used single-cell RNA sequencing (scRNA-seq) to generate datasets encompassing over 60,000 cells from C. acuminata shoot apexes and leaves. After cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Analysis of MIA pathway gene expression revealed that most of them exhibited heightened expression in proliferating cells (PCs) and vascular cells (VCs). In contrast to MIA biosynthesis in Catharanthus roseus, CPT biosynthesis in C. acuminata did not exhibit multicellular compartmentalization. Some putative genes encoding enzymes and transcription factors (TFs) related to the biosynthesis of CPT and its derivatives were identified through co-expression analysis. These include 19 cytochrome P450 genes, 8 O-methyltransferase (OMT) genes, and 62 TFs. Additionally, these pathway genes exhibited dynamic expression patterns during VC and EC development. Furthermore, by integrating gene and transposable element (TE) expression data, we constructed novel single-cell transcriptome atlases for C. acuminata. This approach significantly facilitated the identification of rare cell types, including peripheral zone cells (PZs). Some TE families displayed cell type specific, tissue specific, or developmental stage-specific expression patterns, suggesting crucial roles for these TEs in cell differentiation and development. Overall, this study not only provides novel insights into CPT biosynthesis and spatial-temporal TE expression characteristics in C. acuminata, but also serves as a valuable resource for further comprehensive investigations into the development and physiology of this species.

Single-cell transcriptome profiling reveals the spatiotemporal distribution of triterpenoid saponin biosynthesis and transposable element activity in Gynostemma pentaphyllum shoot apexes and leaves.

Gynostemma pentaphyllum (Thunb.) Makino is an important producer of dammarene-type triterpenoid saponins. These saponins (gypenosides) exhibit diverse pharmacological benefits such as anticancer, antidiabetic, and immunomodulatory effects, and have major potential in the pharmaceutical and health care industries. Here, we employed single-cell RNA sequencing (scRNA-seq) to profile the transcriptomes of more than 50,000 cells derived from G. pentaphyllum shoot apexes and leaves. Following cell clustering and annotation, we identified five major cell types in shoot apexes and four in leaves. Each cell type displayed substantial transcriptomic heterogeneity both within and between tissues. Examining gene expression patterns across various cell types revealed that gypenoside biosynthesis predominantly occurred in mesophyll cells, with heightened activity observed in shoot apexes compared to leaves. Furthermore, we explored the impact of transposable elements (TEs) on G. pentaphyllum transcriptomic landscapes. Our findings the highlighted the unbalanced expression of certain TE families across different cell types in shoot apexes and leaves, marking the first investigation of TE expression at the single-cell level in plants. Additionally, we observed dynamic expression of genes involved in gypenoside biosynthesis and specific TE families during epidermal and vascular cell development. The involvement of TE expression in regulating cell differentiation and gypenoside biosynthesis warrant further exploration. Overall, this study not only provides new insights into the spatiotemporal organization of gypenoside biosynthesis and TE activity in G. pentaphyllum shoot apexes and leaves but also offers valuable cellular and genetic resources for a deeper understanding of developmental and physiological processes at single-cell resolution in this species.

Chrysin mitigated neuropathic pain and peripheral sensitization in knee osteoarthritis rats by repressing the RAGE/PI3K/AKT pathway regulated by HMGB1.

BACKGROUND: Knee osteoarthritis (KOA) is a chronic progressive osteoarthropathy. Chrysin's anti-KOA action has been demonstrated, however more research is needed to understand how chrysin contributes to KOA. METHODS: LPS/ATP-induced macrophages transfected with or without HMGB1 overexpression underwent 5 µg/mL chrysin. The cell viability and macrophage pyroptosis were examined by cell counting kit-8 and flow cytometer. In vivo experiments, rats were injected with 1 mg monosodium iodoacetate by the infrapatellar ligament of the bilateral knee joint to induce KOA. The histological damage was analyzed by Safranin O/Fast Green staining and hematoxylin and eosin staining. The PWT, PWL and inflammatory factors were analyzed via Von-Frey filaments, thermal radiometer and ELISA. Immunofluorescence assay examined the expressions of CGRP and iNOS. The levels of HMGB1/RAGE-, NLRP3-, PI3K/AKT- and neuronal ion channel-related markers were examined by qPCR and western blot. RESULTS: Chrysin alleviated macrophage pyroptosis by inhibiting HMGB1 and the repression of chrysin on HMGB1/RAGE pathway and ion channel activation was reversed by overexpressed HMGB1. HMGB1 facilitated neuronal ion channel activation through the RAGE/PI3K/AKT pathway. Chrysin could improve the pathological injury of knee joints in KOA rats. Chrysin suppressed the HMGB1-regulated RAGE/PI3K/AKT pathway, hence reducing KOA damage and peripheral sensitization. CONCLUSION: Chrysin mitigated neuropathic pain and peripheral sensitization in KOA rats by repressing the RAGE/PI3K/AKT pathway modulated by HMGB1.

Self-assembled core-shell nanoparticles with embedded internal standards for SERS quantitative detection and identification of nicotine released from snus products.

Surface enhanced Raman spectroscopy (SERS) is a unique analytical technique with excellent performance in terms of sensitivity, non-destructive detection and resolution. However, due to the randomness and poor repeatability of hot spot distribution, SERS quantitative analysis is still challenging. Meanwhile, snus is a type of tobacco product that can release nicotine and other components in the mouth without burning, and the rapid detection technique based on SERS can reliably evaluate the amount of nicotine released from snus, which is of great significance for understanding its characteristics and regulating its components. Herein, the strategy was proposed to solve the feasibility of SERS quantitative detection based on self-assembled core-shell nanoparticles with embedded internal standards (EIS) due to EIS signal can effectively correct SERS signal fluctuations caused by different aggregation states and measurement conditions, thus allowing reliable quantitative SERS analysis of targets with different surface affinity. By means of process control, after the Au nanoparticles (Au NPs) were modified with 4-Mercaptobenzonitrile (4-MBN) as internal standard molecules, Ag shell with a certain thickness was grown on the surface of the AuNP@4-MBN, and then the Au@4-MBN@Ag NPs were used to regulate and control the assembly of liquid-liquid interface. The high-density nano-arrays assembled at the liquid-liquid interface ensure high reproducibility as SERS substrates, and which could be used for SERS detection of nicotine released from snus products. In addition, time-mapping research shows that this method can also be used to dynamically monitor the release of nicotine. Moreover, such destruction-free evaluation of the release of nicotine from snus products opens up new perspectives for further research about the impact of nicotinoids-related health programs.

ECM-engineered electrospun fibers with an immune cascade effect for inhibiting tissue fibrosis.

Tissue regeneration/fibrosis after injury is intricately regulated by the immune cascade reaction and extracellular matrix (ECM). Dysregulated cascade signal could jeopardize tissue homeostasis leading to fibrosis. Bioactive scaffolds mimicking natural ECM microstructure and chemistry could regulate the cascade reaction to achieve tissue regeneration. The current study constructed an ECM-engineered micro/nanofibrous scaffold using self-assembled nanofibrous collagen and decorin (DCN)-loaded microfibers to regulate the immune cascade reaction. The ECM-engineered scaffold promoted anti-inflammatory and pro-regenerative effects, M2 polarization of macrophages, by nanofibrous collagen. The ECM-engineered scaffold could release DCN to inhibit inflammation-associated fibrous angiogenesis. Yet, to prevent excessive M2 activity leading to tissue fibrosis, controlled release of DCN was expected to elicit M1 activity and achieve M1/M2 balance in the repair process. Regulated cascade reaction guided favorable crosstalk between macrophages, endothelial cells and fibroblasts by proximity. Additionally, decorin could also antagonize TGF-ß1 via TGF-ß/Smad3 pathway to suppress fibrotic activity of fibroblasts. Hence, ECM-engineered scaffolds could exert effective regulation of the immune cascade reaction by microstructure and DCN release and achieve the balance between tissue fibrosis and regeneration. STATEMENT OF SIGNIFICANCE: With the incidence of up to 74.6%, failed back surgery syndrome (FBSS) has been a lingering issue in spine surgery, which poses a heavy socio-economic burden to society. Epidural fibrosis is believed to be responsible for the onset of FBSS. Current biomaterial-based strategies treating epidural fibrosis mainly rely on physical barriers and unidirectional suppression of inflammation. Regulation of the immune cascade reaction for inhibiting fibrosis has not been widely studied. Based on the simultaneous regulation of M1/M2 polarization and intercellular crosstalk, the ECM-engineered micro/nanofibrous scaffolds constructed in the current study could exert an immune cascade effect to coordinate tissue regeneration and inhibit fibrosis. This finding makes a significant contribution in the development of a treatment for epidural fibrosis and FBSS.

The efficacy and safety of condoliase for lumbar disc herniation: a systematic review and meta-analysis.

Background: Chemonucleolysis is a minimally invasive treatment of lumbar disc herniation (LDH). However, the low specificity of the enzyme and the existence of serious adverse events limit the application of chemonucleolysis. Clinical studies in recent years have shown that Chondroitin sulfate ABC endolyase (condoliase) is a potential therapeutic enzyme for LDH. Aim. A meta-analysis was conducted to determine the efficacy and safety of condoliase in LDH treatment. Methods: We searched Web of Science, Embase, PubMed, and Cochrane Library databases. Two reviewers independently screened articles, extracted data, and assessed the risk of bias. The outcomes were the total effective rate, Oswestry Disability Index (ODI) score change, the proportion of lumbar surgery after condoliase treatment, herniated mass volume change, Pfirrmann grade change, and adverse events. Review Manager 5.3 and Stata 12.0 were used for meta-, sensitivity, and bias analysis. Results: Ten studies were included. A single-arm meta-analysis showed that the total effective rate was 78% [95% confidence interval (CI) 75%-81%], the proportion of surgery was 9% (95% CI 7%-12%), the proportion of Pfirrmann grade change was 43% (95%CI 38%-47%), and the adverse events were 4% (95% CI 2%-6%) after condoliase treatment. The two-arm meta-analysis showed that the ODI score change [standardized mean difference (SMD) -2.46, 95% CI -3.30 to -1.63] and the herniated mass volume change (SMD -16.97, 95% CI -23.92 to -10.03) of the condoliase treatment group were greater than those of the placebo control group, and there was no difference in adverse events between the two groups (OR 1.52, 95% CI 0.60-3.85). The results of sensitivity and publication bias analyses showed that the results were robust. Conclusion: Condoliase intradiscal injection has excellent eutherapeutic and safety for LDH, thus, has considerable potential as a treatment option besides conservative treatment and surgical intervention for LDH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022375492, PROSPERO (CRD42022375492).

The volatile release evaluation of nicotine from snus products under different storage conditions based on surface-enhanced Raman spectroscopy technology.

Surface enhanced Raman spectroscopy (SERS) is a highly sensitive analytical detection technique that provides unique chemical and structural information on target molecules. Snus is a type of tobacco product that can release nicotine and other components under certain humidity and temperature without burning, and the evaluation of its nicotine release under different storage conditions is very important for understanding its characteristics, regulating its components, and setting reasonable storage conditions. Herein, by means of an artificial climate box and suction extraction device, the volatile release evaluations of nicotine from snus products under different storage conditions were performed based on Fe3O4 microparticles coated with Au nanorods and Au nanoparticles (Fe3O4@AuNRsNPs) as SERS substrates combined with a capillary. The Fe3O4@AuNRsNPs assemblies can be fixed in the inner wall of the capillary with the aid of an external magnetic field, which improved the maneuverability of the SERS substrates. By comparing the intensities of the spectral peaks of the symmetrical breathing of the pyridine moiety of nicotine molecules with increasing temperature and humidity, which could significantly accelerate the volatile release of a small amount of nicotine, the nicotine release under different conditions could be evaluated. Based on this strategy, it was possible to obtain the storage or placement conditions of the product. The results of this study provide a reference to clarify the volatile release of nicotine under various storage conditions, which is helpful for better regulation of the levels of nicotine in snus. Moreover, such destruction-free evaluation of the volatile release of nicotine from snus products under different storage conditions opens up new perspectives for further research about the impact of nicotinoids on smokers' health and cessation programs.

Integrated transcriptome and proteome analysis provides new insights into camptothecin biosynthesis and regulation in Camptotheca acuminata.

Camptotheca acuminata Decne., the main source of camptothecin (CPT), has received increasing attention for its remarkable antitumor activity. Many CPT derivatives are clinically used as effective anticancer agents worldwide. However, their biosynthesis mechanism remains unclear, and uncovering this pathway would greatly facilitate development of alternative CPT production methods to replace current inefficient plant-derived ones. The expression of >30,000 genes was accurately quantified using unique molecular identifier RNA sequencing in 10 C. acuminata tissues, and 7854 proteins from five tissues were quantified with label-free quantitative proteomics. Fifteen full-length transcriptomes were sequenced with long-read Oxford Nanopore Technologies, and 5692 alternative splicing events were discovered among 4746 genes. Integrated transcriptome and proteome analysis provided novel insights into CPT biosynthesis and its hierarchical regulation. Five cytochrome P450s and three O-methyltransferases were considered as candidates involved in the biosynthesis of CPT and its derivatives, while 15 transcription factors potentially regulating CPT biosynthesis were screened. These findings provide important clues for elucidating the biosynthetic mechanisms of CPT and its derivatives and substantially contribute to the future production of these anticancer agents with synthetic biology. The generated large-scale multiomics data also provide valuable resources for investigating the functional genomics of the most important CPT-producing plant species-C. acuminata.

Licorice Germplasm Resources Identification Using DNA Barcodes Inner-Variants.

Based on the gradual transformation from wild growth to artificial cultivation, the accurate authentication of licorice seeds contributes to the first committed step of its quality control and is pivotal to ensure the clinical efficacy of licorice. However, it is still challenging to obtain genetically stable licorice germplasm resources due to the multi-source, multi-heterozygous, polyploid, and hybrid characteristics of licorice seeds. Here, a new method for determining the heterozygosity of licorice seed mixture, based on the various sites, and finding the composition characteristics of licorice seed is preliminarily designed and proposed. Namely, high-throughput full-length multiple DNA barcodes(HFMD), based on ITS multi-copy variation exist, the full-length amplicons of ITS2, psbA-trnH and ITS are directly sequenced by rDNA through the next-generation sequence(NGS) and single-molecule real-time (SMRT) technologies. By comparing the three sequencing methods, our results proved that SMRT sequencing successfully identified the complete gradients of complex mixed samples with the best performance. Meanwhile, HFMD is a brilliant and feasible method for evaluating the heterozygosity of licorice seeds. It shows a perfect interpretation of DNA barcoding and can be applied in multi-base multi-heterozygous and polyploid species.

Intra-Articular Injection of miR-29a-3p of BMSCs Promotes Cartilage Self-Repairing and Alleviates Pain in the Rat Osteoarthritis.

BACKGROUND: Stem cells intra-articular injection stagey indicated a potential therapeutic effect on improving the pathological progress of osteoarthritis (OA). However, the long-term effect of stem cells intra-articular injection on the cartilage regeneration remains unclear. miR-29a-3p is predicted to be a critical target for inhibiting insulin-like growth factor-1 expression and may aggravate the progression of OA. METHODS: In this study, we investigated the therapeutic efficacy of intra-articular injection of bone marrow mesenchymal stem cells (BMSCs) transfected with miR-29a-3p inhibitor in OA. RESULTS: miR-29a-3p inhibitor transfection did not influence cell viability of BMSCs, while the chondrogenic differentiation potential of BMSCs was significantly improved. Interestingly, intra-articular injection of BMSCs with miR-29a-3p inhibition significantly prevented articular cartilage degeneration by up-regulating the expression of Sox 9, Col-2a1, aggrecan and down-regulating the expression of matrix metalloproteinase, as well as relieved pain in OA. CONCLUSION: The double effects on cartilage protection and pain relief indicated a great potential of intra-articular injection of miR-29a-3p inhibitor-transfected BMSCs for the treatment of OA.

Demethoxycucumin protects MDA-MB-231 cells induced bone destruction through JNK and ERK pathways inhibition.

Bone is the most common late metastasis of breast cancer. Bone metastasis causes not only severe bone pain, but also bone-related diseases such as pathological fractures, which are closely related to osteoclasts. The effects of demethoxycurcumin (DMC) on osteoclast biology has not been investigated. In this study, we explored the effects of DMC on MDA-MB-231 cells, MCF-7 cells, and osteoclasts induced by RANKL in vitro, as well as the protective effect on bone destruction of tumor bone metastasis in vivo. DMC showed inhibitory effect on the migration and promotes the apoptosis of MDA-MB-231 and MCF-7 cells. At the same time, DMC inhibited osteoclast maturation and mature osteoclast bone resorption in a dose-dependent manner, and suppressed the expression of osteoclast marker genes TRAP, CTSK, MMP9, V-ATPase-d2 and DC-STAMP significantly. Biochemical data showed that DMC inhibited tumor cells and osteoclasts by inhibiting the early activation of ERK and JNK MAPK pathway. Consistent with the results in vitro, we confirmed that DMC protects bone destruction caused by tumor metastasis in vivo. In short, our study confirmed that DMC could be used as a potential drug for the treatment of tumor bone destruction.

Programmed intermittent epidural bolus decreases the incidence of intra-partum fever for labor analgesia in primiparous women: a randomized controlled study.

PURPOSE: To evaluate whether programmed intermittent epidural bolus (PIEB) reduces the incidence of maternal intra-partum fever compared with continuous epidural infusion (CEI) during labor. METHODS: Parturients were randomized to receive CEI (CEI group) or PIEB (PIEB group) with 10 ml per hour for epidural labor analgesia with 1500 subjects in each group. The maintaining dose of two groups is 0.08% ropivacaine with 0.4 µg/ml sufentanil, with patient-controlled epidural analgesia (PCEA) dose of 5 ml and lockout interval of 30 min. The incidence of maternal fever, pain score, epidural sensory levels, the number and proportion of PCEA demand, anesthetics consumption, satisfaction score, neonatal Apgar scale, and maternal and neonatal side effects were recorded. RESULTS: It was significantly lower of the incidence of maternal fever beginning at 4 h post-analgesia and continuing until delivery in the PIEB group than the CEI group (4 h: 2.6% vs. 4.2%; 5 h: 7.3% vs. 10.2%; delivery: 5.6% vs. 7.9%; 1 h post-delivery: 3.9% vs. 6.2%; 2 h post-delivery: 2.1 vs. 3.5%; total: 5.8% vs. 8.4% in PIEB and CEI, respectively). Compared with CEI group, pain scores at 3, 4, 5 h post-analgesia and delivery (3 h: 2 [1, 2] vs. 2 [1-3]; 4 h: 2 [2, 3] vs. 3 [2-4]; 5 h: 2 [2, 3] vs. 3 [2-4]; delivery: 3 [2-4] vs. 4 [3, 4] in PIEB and CEI, respectively), the number and proportion of PCEA demand (number: 0.7 ± 0.9 vs. 2.2 ± 1.9; proportion: 42.0% vs. 80.3% in PIEB and CEI, respectively), and anesthetics consumption significantly decreased in the PIEB group (Ropivacaine: 60 ± 13 mg vs. 76 ± 17 mg; Sufentanil: 26 ± 4 mg vs. 32 ± 6 mg in PIEB and CEI, respectively), without severe maternal and neonatal side effects and any difference in neonatal Apgar scale. The epidural sensory levels 2 h post-analgesia (2 h: 8[8, 9] vs. 9[8, 9] in PIEB and CEI) and satisfaction score (9 [9, 10] vs. 7 [6, 7] in PIEB and CEI) were significantly higher in the PIEB group compared with those in the CEI group. CONCLUSIONS: PIEB with 10 ml of 0.08% ropivacaine and 0.4 µg/ml sufentanil hourly provided a lower incidence of intra-partum fever with a better analgesic effect compared with CEI, without any severe maternal and neonatal adverse reactions.

Pancreatic carcinoma underlying a complex presentation in late pregnancy: a case report.

BACKGROUND: Gestational diabetes mellitus is strongly related to the risk of pancreatic cancer in pregnant women, but gestational diabetes can precede a diagnosis of pancreatic cancer by many years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1. Pancreatic adenocarcinoma is one of the most common malignancies associated with thromboembolic events. A clinical study showed that thromboembolic events were detected in 36% of patients diagnosed as having pancreatic cancer. Studies showed that gestational diabetes mellitus could be one of the important risk factors for pancreatic cancer. CASE PRESENTATION: Gestational diabetes mellitus is associated with increased risk of breast and pancreatic cancer. This case report describes a 29-year-old Chinese woman who presented with: gestational diabetes mellitus; International Society on Thrombosis and Haemostasis criteria suggested disseminated intravascular coagulation with a score of 5; hemolysis, elevated liver enzymes, low platelet count syndrome; and pulmonary hypertension. After an intravenous injection of fibrinogen, she gave birth to a normal baby and following delivery, her blood pressure reached 180/110 mmHg. Laboratory analysis results showed elevated lactic dehydrogenase, decreased platelets and fibrinogen, and urine protein was positive. She was transfused with fresh frozen plasma, blood coagulation factor, and fibrinogen. Subsequently, she was transferred to a maternity intensive care unit, where magnesium sulfate seizure prophylaxis was continued for 24 hours to keep her magnesium level at a low therapeutic range. However, continuous oxygen therapy was needed to maintain her oxygenation. Further laboratory investigations revealed elevated carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4. Positron emission tomography-computed tomography showed malignant carcinoma in the head of her pancreas with lymph node involvement along with bone, peritoneal, and left adrenal metastasis, as well as double lung lymphangitic carcinomatosis. CONCLUSION: A differential diagnosis of digestive system neoplasm should be considered when a pregnant patient presents with gestational diabetes mellitus and disseminated intravascular coagulation, where the disseminated intravascular coagulation has no specific cause and cannot be readily resolved.

[Treatment of thoracolumbar fractures with three-dimensional reduction method and external fixation devices under analgesia].

OBJECTIVE: To compare the clinical effects between open reduction internal fixation and three-dimensional reduction with external fixation under analgesia in treating fresh thoracolumbar fractures, and explore the simple and effective method for thoracolumbar fractures. METHODS: The clinical data of 40 patients with thoracolumbar fractures who met the inclusion and exclusion criteria in the department of orthopaedics affiliated to Suzhou Hospital of Nanjing University of Chinese Medicine from February 2013 to August 2017 were retrospectively analyzed. According to therapeutic methods, the patients were devided into treatment group and control group, 20 cases in each group. Treatment group was treated by three-dimensional reduction method and external fixation devices under analgesia, and control group was treated by open reduction and common spinal fixation system. In treatment group, there were 9 males and 11 females, aged from 26 to 68 years old with an average of (52.8±11.3) years; and in control group, there were 10 males and 10 females, aged from 26 to 64 years old with an average of(50.6±8.8) years. Anterior vertebral body compression(AVBC), Cobb angle and visual analogue scale(VAS) were measured and compared in two group. RESULTS: All 40 patients finished follow-up. The follow-up time in treatment group was 5 to 37 months with average of (16.1±8.8) months, in control group was 5 to 29 months with an average of(17.3±6.0) months. There was no significant difference between two groups(P>0.05). AVBC, Cobb angle, VAS score were obviously improved in all patients after treatment(P<0.05), but there were no significant difference between two groups(P>0.05). CONCLUSIONS: Clinical effect of two methods was similar in treating thoracolumbar fractures, but three-dimensional reduction and external fixation devices under analgesia has advantage of easy operation, smaller trauma and no need secondary surgery for removed internal fixation.

NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL-mediated extrinsic signaling pathway.

Nuclear factor of activated T cells (NFAT) is a family of transcription factors that have important functions in many tumors. However, the expression level and functional role of NFAT in hepatocellular carcinoma (HCC) remain unclear. In this study, we showed that NFATc1 expression was decreased in both HCC tissues and cell lines. Low expression of NFATc1 was correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, high serum AFP level, and liver cirrhosis. Furthermore, patients with low NFATc1 expression exhibited poor prognosis. Ectopic expression of NFATc1 in HCC cells inhibited proliferation and colony formation, leading to G1 arrest and induction of apoptosis. In addition, we demonstrated that NFATc1 increased Fas ligand (FasL) expression by directly binding to its promoter and activated the extrinsic apoptotic pathway. NFATc1 and FasL expression patterns and their prognostic value for patients with HCC were also evaluated in TCGA Liver Hepatocellular Carcinoma database. Knock-down of FasL expression by siRNA in HCC cell lines abolished NFATc1's antiproliferative and pro-apoptotic effects. In conclusion, NFATc1 is frequently inactivated in HCC and functions as a tumor suppressor in liver carcinogenesis. Ectopic expression of NFATc1 in HCC cells induces apoptosis by activating the FasL-mediated extrinsic signaling pathway.

Analysis of crotonaldehyde puff-by-puff release in mainstream cigarette smoke under various smoking regimens by high-performance liquid chromatography with the modified QuEChERS method.

To study puff-by-puff release characteristics of crotonaldehyde in mainstream cigarette smoke under diverse intensive smoking regimens, we designed an RM20H smoking machine with a puff-by-puff smoke collection unit to automatically trap crotonaldehyde in the mainstream cigarette smoke. Using this process, we trapped, puff-by-puff, crotonaldehyde in mainstream smoke generated by different smoking regimens and quantitatively analysed the levels of crotonaldehyde using high-performance liquid chromatography with a modified QuEChERS sample pretreatment method. On the basis of the crotonaldehyde in each puff, we determined crotonaldehyde's puff-by-puff release characteristics. The results showed that crotonaldehyde's puff-by-puff release remained nearly constant for the International Organization for Standardization mode while increased polynomial trend was seen (n ≥ 6) under the Massachusetts and Health Canada smoking regimens. The equation fit for various regimens was good (R2 > 0.9192). Release characteristics by puff were classified into four categories: (1) first, second and third puffs; (2) fourth and fifth puffs; (3) sixth puff; and (4) seventh and eighth puffs.

Dexmedetomidine Added to Sufentanil Patient-Controlled Intravenous Analgesia Relieves the Postoperative Pain after Cesarean Delivery: A Prospective Randomized Controlled Multicenter Study.

This study evaluated the efficacy and safety of dexmedetomidine in intravenous patient-controlled analgesia (PCA) after cesarean delivery. This multicenter study enrolled 208 subjects who were scheduled for selective cesarean delivery from 9 research centers. Patients received 0.5 ug/kg dexmedetomidine (study group) or normal saline (control group) after delivery and an intravenous PCA pump after surgery (100 µg sufentanil +300 µg dexmedetomidine for the study group, 100 µg sufentanil for the control group, background infusion: 1 ml/h, bolus dose: 2 ml and lock time: 8 min). The sufentanil consumption, pain scores, rescue analgesia, sedation scores, analgesic satisfaction, the incidence of postoperative nausea and vomiting (PONV) and the first passage of flatus were recorded within 24 h after surgery. The sufentanil consumption in the study group was significantly lower than that in the control group (p = 0.004). Compared with the control group, the study group had lower pain scores (p < 0.01), higher analgesic satisfaction degree [p < 0.001, odd ratio 4.28 and 95% CI (2.46, 7.46)], less requirement of rescue analgesia (p = 0.003), lower incidence of PONV (p = 0.005 and p < 0.001, respectively), and shorter time to first passage of flatus (p = 0.007). Dexmedetomidine added to sufentanil intravenous PCA significantly enhanced the analgesic effects, improved analgesic satisfaction, and had the potential benefits of reducing PONV and the recovery of intestinal functions after cesarean section.

A new mononuclear neutral high-spin iron(III) complex with the different tridentate ligands 5-bromo-salicyl-aldehyde (pyridin-2-yl)hydrazone and 5-bromo-salicyl-aldehyde thio-semicarbazone.

The title neutral mononuclear complex, [1-(5-bromo-2-oxido-benzyl-idene)thio-semicarbazidato](4-bromo-2-{[2-(pyridin-2-yl)hydrazinyl-idene]meth-yl}pheno-lato)iron(III), [Fe(C8H6BrN3OS)(C12H9BrN3O)] (I), crystallizes in the monoclinic space group C2/c and has two different planar tridentate ligands. The central FeIII ion is coordinated to three N, two O and one S atom, forming a distorted octa-hedral FeN3O2S coordination geometry. In the crystal, the complex mol-ecules are linked by N-H⋯O and N-H⋯N hydrogen bonds and π-π inter-actions into layers parallel to (100). Magnetic measurements show that the central FeIII ion is in the high-spin state; this is also supported by the bond distances around the FeIII ion.

Recombinant human platelet-derived growth factor-BB versus autologous bone graft in foot and ankle fusion: A systematic review and meta-analysis.

Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.

In vitro evaluation of electrospun silk fibroin/nano-hydroxyapatite/BMP-2 scaffolds for bone regeneration.

Bone tissue engineering by using osteoinductive scaffolds seeded with stem cells to promote bone extracellular matrix (ECM) production and remodeling has evolved into a promising approach for bone repair and regeneration. In order to mimic the ECM of bone tissue structurally and compositionally, nanofibrous silk fibroin (SF) scaffolds containing hydroxyapatite (HAP) nanoparticles and bone morphogenetic protein 2 (BMP-2) were fabricated in this study using electrospinning technique. The microstructure, mechanical property, biocompatibility, and osteogenic characteristics were examined. It was found that the HAP nanoparticles were successfully incorporated in the SF nanofibers (diameter, 200-500 nm). The mechanical properties of SF/HAP/BMP-2 composite scaffolds increased with HAP content when it was less than 20 wt%, after which the mechanical properties dropped as HAP content increased. Cell culture tests using bone marrow mesenchymal stem cells (BMSCs) showed that the scaffolds had good biocompatibility and promoted the osteogenic differentiation of BMSCs. Therefore, the electrospun SF/HAP/BMP-2 scaffolds may serve as a promising biomaterial for bone tissue engineering.