Total Synthesis of the Racemate of Laurolitsine.

The total synthesis of laurolitsine was achieved for the first time. This reaction was accomplished in 14 steps with a 2.3% yield (this was calculated using 3-hydroxy-4-methoxybenzaldehyde as the starting material) starting from two simple materials, 3-hydroxy-4-methoxybenzaldehyde and 2-(3-hydroxy-4-methoxyphenyl)acetic acid, and the longest linear sequence consisted of 11 steps. The key steps included an electrophilic addition reaction in which a nitro group was reduced to an amino group using lithium tetrahydroaluminum and a Pd-catalyzed direct biaryl coupling reaction. In this paper, many of the experimental steps were optimized, and an innovative postprocessing method in which 2-(3-(benzyloxy)-4-methoxyphenyl)ethanamine is salted with oxalic acid was proposed.

The effects of vitamin D on all-cause mortality in different diseases: an evidence-map and umbrella review of 116 randomized controlled trials.

Purpose: To conduct a solid evidence by synthesizing meta-analyses and updated RCTs about the effects of vitamin D on all-cause mortality in different health conditions. Methods: Data sources: Pubmed, Embase, Web of Science, the Cochrane Library, Google Scholar from inception until 25th April, 2022. Study selection: English-language, meta-analyses and updated RCTs assessing the relationships between vitamin D and all-cause mortality. Data synthesis: Information of study characteristics, mortality, supplementation were extracted, estimating with fixed-effects model. A Measurement Tool to Assess Systematic Reviews, Grading of Recommendations Assessment, Development and Evaluation, and funnel plot was used to assess risk of bias. Main outcomes: All-cause mortality, cancer mortality, cardiovascular disease mortality. Results: In total of 27 meta-analyses and 19 updated RCTs were selected, with a total of 116 RCTs and 149, 865 participants. Evidence confirms that vitamin D reduces respiratory cancer mortality (RR, 0.56 [95%CI, 0.33 to 0.96]). All-cause mortality is decreased in patients with COVID-19 (RR, 0.54[95%CI, 0.33 to 0.88]) and liver diseases (RR, 0.64 [95%CI, 0.50 to 0.81]), especially in liver cirrhosis (RR, 0.63 [95%CI, 0.50 to 0.81]). As for other health conditions, such as the general health, chronic kidney disease, critical illness, cardiovascular diseases, musculoskeletal diseases, sepsis, type 2 diabetes, no significant association was found between vitamin D and all-cause mortality. Conclusions: Vitamin D may reduce respiratory cancer mortality in respiratory cancer patients and all-cause mortality in COVID-19 and liver disorders' patients. No benefits showed in all-cause mortality after vitamin D intervention among other health conditions. The hypothesis of reduced mortality with vitamin D still requires exploration. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=252921, identifier: CRD42021252921.

Exploring the Interrelationships between Public Health, Fiscal Decentralization, and Local Government Debt in China.

This paper investigates the interrelationships among local government debt, fiscal decentralization, and public health. The investigation begins by constructing a theoretical model to analyze the inherent connections between these variables. Subsequently, an empirical analysis is conducted using data from China between 2015 and 2021. The findings demonstrate a bidirectional relationship between fiscal decentralization, local government debt, and public health. Specifically, it is observed that an increase in local government debt has adverse effects on both fiscal decentralization and public health, while fiscal decentralization has a positive impact on public health. These insights are consistently validated through rigorous regression methodologies, affirming the robustness and significance of these relationships.

New aphidicolane diterpenoids with glucose consumption promoting and cell viability enhancing activities from Scoparia dulcis.

Two new aphidicolane diterpenoids, termed Scopadulinol A (1) and B (2), were obtained from whole plants of Scoparia dulcis. Their structures were elucidated by applying various spectroscopic techniques, including 1D- and 2D-NMR and HR-ESI-MS. The absolute configurations of 1 and 2 were determined by applying the calculated electronic circular dichroism (ECD). In addition, both compounds were tested for their effects on glucose consumption in HL-7702 cells and on palmitic acid (PA) induced viability in MIN6 cells at different concentrations. The results showed that they significantly promoted glucose consumption and attenuated the PA-induced decrease of cell viability. Additionally, 2 was tested to determine whether it could activate AMP-activated protein kinase (AMPK), but it showed no such effect at the tested dosage. These results indicated that the new compounds might promote glucose consumption through other pathways but not by activating AMPK. Collectively, we highlighted the isolation of two new aphidicolane diterpenoids from S. dulcis and found that they could promote glucose consumption and attenuate PA-induced decrease of cell viability.

Self-Assembled KLD-12/SDF-1 Polypeptide Promotes Differentiation and Migration of BMSCs via the Wnt/ß-catenin Signaling Pathways.

OBJECTIVE: This study aimed to evaluate the combination of SDF-1 and KLD-12 to form self-assembling polypeptide and its effect on osteogenic differentiation. METHODS: ELISA assay was performed to detect whether KLD-12 composite SDF-1 self-assembled polypeptide was successfully prepared. BMSCs were isolated and characterized by Flow cytometry. MTT assays, Calcein-AM/PI fluorescence staining, and Glycosaminoglycans (GAGs) measurement were carried out to detect cell viability after cells exposed to KLD-12 composite SDF-1 selfassembled polypeptide. The migration of cells induced by KLD-12 composite SDF-1 selfassembled polypeptide was also examined by transwell assay and Immunoblot. Osteogenic differentiation of cells stimulated with KLD-12 composite SDF-1 self-assembled polypeptide was analyzed by Immunoblot, Alizarin Red Staining, and Alkaline Phosphatase activity. Additionally, immunoblot and immunofluorescence assays were performed to investigate the effects of the polypeptide on the Wnt/ß-catenin pathway. RESULTS: KLD-12 composite SDF-1 self-assembled polypeptide was successfully prepared and identified. In addition, we isolated and characterized mouse mesenchymal stem BMSCs. Our data further revealed that KLD-12 combined with SDF-1 self-assembled polypeptide improved the survival of BMSCs and promoted cell migration. Moreover, the self-assembled polypeptide induced osteogenic differentiation of BMSCs. Mechanically, we found that the self-assembled polypeptide activated the Wnt/ß-catenin pathway, therefore promoting the differentiation and migration of BMSCs. CONCLUSION: Our proposed treatment can potentially be effective for bone defects.

NLR value and IL-18 level and their clinical significance in patients with deep vein thrombosis after receiving the surgery for spinal degeneration.

OBJECTIVE: To investigate the value of the neutrophil-to-lymphocyte ratio (NLR) and Interleukin 18 (IL-18) level in patients with deep vein thrombosis after receiving surgery for spinal degeneration; and we explore their significance in clinical practice. METHODS: This study was conducted in 296 patients who were treated in our hospital for spinal degeneration. After surgery, these patients were followed up for 1 month. After performing the color Doppler ultrasound examination, patients were divided into the thrombus group (n = 72) and the non-thrombus group (n = 224) based on the occurrence of deep vein thrombosis. Baseline data, NLR values and IL-18 levels before surgery, and at 1, 3, 5, and 7 days after surgery were compared between the two groups. Logistic regression analysis was implemented to analyze the risk factors for postoperative deep vein thrombosis. Patients in the thrombosis group were allocated to the mild, moderate, and severe group on the basis of the degree of thrombosis. NLR values and IL-18 levels at 3 days after surgery were compared among the three groups. The correlations between both NLR value and IL-18 level and the severity of deep vein thrombosis were analyzed with Pearson correlation. Receiver operating characteristic curve was used to assess the clinical value of NLR value and IL-18 level at 3 days after surgery in predicting postoperative deep vein thrombosis. RESULTS: There were significant differences concerning age, the history of diabetes, and obesity between the two groups (all P<0.05). NLR values and IL-18 levels in both groups after surgery were increased when compared with before surgery (all P<0.01). In addition, NLR values and IL-18 levels reached a peak at 3 days after surgery. Compared with the non-thrombus group, NLR values and IL-18 levels in the thrombus group at 1, 3, 5, and 7 days after surgery were increased (all P<0.01). NLR value and IL-18 level in the thrombosis group at 3 days after surgery were increased with a worsened degree of thrombosis. In other words, both NLR value and IL-18 level were positively correlated with the degree of deep vein thrombosis. The results of logistic regression analysis displayed that age ≥60 years old, body mass index ≥23 kg/m2, NLR value >4.34%, and IL-18 level >115.71 ng/mL were independent risk factors for postoperative deep vein thrombosis. The results of the ROC curve showed that the area under curves, which represent the formation of postoperative deep vein thrombosis, were above 0.7 when using NLR value and IL-18 level at 3 days after surgery (both P<0.001). CONCLUSION: Compared with the non-thrombus group, NLR value and IL-18 level in the thrombosis group after receiving surgery for spinal degeneration are significantly increased. In addition, the more severe the thrombosis is, the higher the NLR value and IL-18 level at 3 days after surgery. Therefore, NLR value and IL-18 level at 3 days after surgery have certain clinical value in predicting postoperative deep vein thrombosis and prognosis.

Ilizarov bone transport to treat infected nonunion of long bones: a multicenter retrospective cohort study.

OBJECTIVE: To examine the efficacy and safety of Ilizarov bone transport in the treatment of infected nonunion of long bones. METHODS: Patients who underwent Ilizarov bone transport for treatment of bone nonunion with chronic osteomyelitis in the three largest regional orthopedic trauma centers in China from July 2013 to July 2018 were retrospectively examined. Treatment results were evaluated with Paley's criteria for bone healing and functional assessment. RESULTS: In total, 189 patients were treated during the study period. The study population comprised 135 male and 54 female patients with an average age of 37.5 years (range, 11-61 years). The patients were followed up for at least 24 months. According to Paley's criteria for bone healing and functional assessment, the bone healing results were excellent in 115 (61%) patients, good in 31 (16%), fair in 21 (11%), and poor in 22 (12%). The functional evaluation results were excellent in 76 (40%) patients, good in 65 (34%), fair in 22 (11%), poor in 26 (14%). CONCLUSION: Infected nonunion of long bones can be effectively and safely treated with Ilizarov bone transport.

A neural network-based joint learning approach for biomedical entity and relation extraction from biomedical literature.

Recently joint modeling methods of entity and relation exhibit more promising results than traditional pipelined methods in general domain. However, they are inappropriate for the biomedical domain due to numerous overlapping relations in biomedical text. To alleviate the problem, we propose a neural network-based joint learning approach for biomedical entity and relation extraction. In this approach, a novel tagging scheme that takes into account overlapping relations is proposed. Then the Att-BiLSTM-CRF model is built to jointly extract the entities and their relations with our extraction rules. Moreover, the contextualized ELMo representations pre-trained on biomedical text are used to further improve the performance. Experimental results on biomedical corpora show that our method can significantly improve the performance of overlapping relation extraction and achieves the state-of-the-art performance.

Serum galectin-3 concentrations in patients with ankylosing spondylitis.

OBJECTIVE: The aim of our study was to assess potential correlations between serum galectin-3 concentrations and Ankylosing Spondylitis Disease Activity (ASDAS) index in patients with ankylosing spondylitis (AS). METHODS: A total of 112 patients with AS were included, and 130 healthy subjects were considered as controls. We collected the detailed medical history, and ASDAS index was used to assess the disease severity in patients with AS. RESULTS: The serum galectin concentrations were higher in AS patients compared to the health groups (14.1 ± 9.6 vs 9.2 ± 3.7, P < 0.001). The correlation analysis showed that serum galectin concentrations were significantly positively correlated with C-reactive protein and erythrocyte sedimentation rate (r = 0.369, P < 0.001; r = 0.240, P = 0.011). In addition, the positively correlation of serum galectin-3 with global pain index (r = 0.238, P = 0.011) was observed in AS patients. A significant positively correlation between serum galectin and ASDAS index in AS patients was found (r = 0.367; P < 0.001). In multiple linear regression analysis, the results indicated that increased serum galectin still was correlated with ASDAS index (r = 0.322, P < 0.001) in patients with AS. CONCLUSIONS: Serum galectin concentrations were found to be correlated with ASDAS index in patients with AS.

[Case-control study on modified Weaver-Dunn surgery combined with clavical hook-plate internal fixation for the treatment of Tossy type III acromioclavicular dislocation].

OBJECTIVE: To compare therapeutic effects of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation in treating Tossy type III acromioclavicular joint dislocation. METHODS: Forty-one patients with Tossy type III acromioclavicular dislocation treated by operation were retrospectively analysis from January 2012 to January 2014. The patients were divided into clavicular hook-plate fixation group (group A) and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation (group B) according to surgical procedures. In group A, there were 15 males and 6 females aged from 17 to 51 years old with an average of (31.60 ± 12.58) years old, preoperative Constant-Murley score was 40.25 ± 9.80, and treated with clavicular hook-plate fixation. In group B, there were 13 males and 7 females aged from 18 to 48 years old with an average of (29.40 ± 11.27) years old, preoperative Constant-Murley score was 41.45 ± 8.81, and treated with modified Weaver-Dunn surgery combined with clavicular hook-plate fixation. Operative time, blood loss, imaging changes before and after operation, postoperative complications were compared; Constant-Murley score at 3, 6 and 12 months after operation were evaluated. RESULTS: In group A, operative time was 40.50 ± 24.36) min, blood loss was (75.30 ± 30.36) ml; In group B, operative time was (60.10 ± 23.55) min, blood loss was (100.70 ± 40.12) ml. Twenty-one patients in group A were followed-up from 12 to 18 months with an average of (14.8 ± 3.1) months; 20 patients in group B were followed-up from 12 to 14 months with an average of (13.6 ± 1.5) months. There were no significant differences in operative time, blood loss and follow-up time between two groups. Complications were in six patients of group A and 3 patients of group B, and there were no significant meaning between two groups. At 6 months after operation, Constant-Murley score in group A was 88.85 ± 4.23, 92.15 ± 3.82 in group B; and had significant meaning between two groups (t = -2.56, P = 0.022 < 0.05). While there were no differences in Constant-Murley score in other times. CONCLUSION: Both of clavicular hook-plate fixation and modified Weaver-Dunn surgery combined with clavicular hook-plate fixation are effective operative methods for the treatment of Tossy type III acromioclavicular dislocation. Clavicular hook-plate fixation has advantage of less trauma, while modified Weaver-Dunn surgery combined with clavicular hook-plate fixation could reconstruct coracoclavicular ligament more stronger, clavicular hook plate could take out earlier, also improve shoulder joint function earlier.

11-Phenyl-[b,e]-dibenzazepine compounds: novel antitumor agents.

A series of 11-phenyl-[b,e]-dibenzazepine compounds were synthesized and shown to be inhibitors of tumor cell proliferation with IC(50) values ranging from submicromolar to micromolar concentrations. Flow cytometric analyses of several active compounds demonstrated inhibition of cell cycle progression at the G(0)-G(1) phase transition resulting in G(0)-G(1) arrest.

NC381, a novel anticancer agent, arrests the cell cycle in G0-G1 and inhibits lung tumor cell growth in vitro and in vivo.

Although clotrimazole (CLT), an antifungal drug, inhibits tumor cell proliferation and angiogenesis, its clinical application is hampered by significant hepatotoxicity due to the presence of an imidazole moiety. In our attempts to develop CLT analogs that are devoid of imidazole and are as efficacious as CLT, one pharmacophore designated NC381 was generated and shown to inhibit tumor cell growth via a mechanism similar to that of CLT. In vitro, treatment of NCI-H460 nonsmall cell lung cancer (NSCLC) cells with NC381 inhibited growth in a time-dependent manner. Flow cytometric analysis demonstrated that the decrease in cell growth was associated with inhibition of cell cycle progression at the G(1)-S phase transition, resulting in G(0)-G(1) arrest. There was a concomitant inhibition of cyclin D1 expression and subsequent reduction in the formation of the cyclin D1-CDK4 complex. Consistent with a decrease in the cyclin D1-CDK4 complex, NC381 treatment resulted in significant inhibition of pRb phosphorylation. There also were changes in the activity of cell cycle-related proteins, including p16(Ink4) and p27(Kip1). Together, these results are consistent with a model in which NC381 arrests cell cycle progression via inhibition of the pathway that promotes exit from the G(1) phase of the cell cycle. Furthermore, the clinical applicability of NC381 was evaluated in an in vivo murine xenograft model of human NSCLC (NCI-H460). NC381 treatment resulted in significant inhibition of tumor growth. Given the poor prognosis and the limited treatment options available, the present results underscore the potential of NC381 in the treatment of human NSCLC.

Adenovirus-mediated ribonucleotide reductase R1 gene therapy of human colon adenocarcinoma.

Ribonucleotide reductase is the enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides for DNA synthesis. Ribonucleotide reductase is a multisubunit complex containing two polypeptides, R1 and R2. In addition to catalytic and allosteric regulatory functions, the R1 subunit appears to act as a novel tumor suppressor. Previous studies demonstrated that overexpression of mouse R1 resulted in suppression of tumorigenicity and metastatic potential, whereas expression of antisense RNA, complementary to R1 mRNA, increased anchorage-independent growth of ras-transformed NIH 3T3 cells. The current study investigated the potential of R1 gene therapy for human cancer using a recombinant adenovirus encoding the human R1 gene (rAd5-R1). Recombinant viruses were constructed by FLP-mediated site-specific recombination and demonstrated high infectivity of a human colon carcinoma cell line (Colo320 HRS), as assessed by expression of a viral encoded beta-Gal gene (rAd5-LacZ). R1mRNA and protein were overexpressed in Colo320 HRS cells infected with rAd5-R1 compared with untreated or rAd5-LacZ-infected cells. Infection with rAd5-R1 inhibited Colo320 HRS cell proliferation, in vitro, in a time- and dose-dependent manner. When Colo320 HRS cells were treated with rAd5-R1, before injection into CD-1 mice, there was complete inhibition of tumor growth compared with treatment with rAd5-LacZ. Furthermore, intratumoral injection of rAd5-R1 into Colo320 HRS tumor xenografts inhibited tumor growth in CD-1 mice compared with rAd5-LacZ treated mice (P = 0.0001). These results demonstrate gene-specific antitumor effects of R1 and suggest that rAd5-R1 gene therapy has the potential to improve currently available treatments for colon cancer.