Discovery and Biomimetic Synthesis of a Polycyclic Polymethylated Phloroglucinol Collection from Rhodomyrtus tomentosa.

Inspired by a previously reported biomimetic synthesis study, four new naturally occurring phloroglucinol trimers 1-4 with unusual 6/5/5/6/6/6-fused hexacyclic ring systems, along with two known analogues (5 and 6) and two known biogenetically related dimers (10 and 11), were isolated from Rhodomyrtus tomentosa. Their structures and absolute configurations were unambiguously elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism calculation. By mimicking two potentially alternative biosynthetic pathways, the first asymmetric syntheses of 1-4 and the racemic syntheses of 5 and 6 were achieved in only five to six steps without the need for protecting groups. Furthermore, phloroglucinol dimers 10 and 11 exhibited significant in vitro antiviral activity against the respiratory syncytial virus.

Expeditious assembly of biuret-guanidine derivatives via the catalyst-free transformation.

We disclose a mild and practical catalyst-free transformation for the expeditious construction of biuret-guanidine derivatives using aromatic isocyanates. This synthetic transformation is featured with mild reaction conditions and high efficiency.

Pyridazino[1,6-b]quinazolinones as new anticancer scaffold: Synthesis, DNA intercalation, topoisomerase I inhibition and antitumor evaluation in vitro and in vivo.

A new anticancer N-containing heterocyclic scaffold was designed and 30 pyridazino[1,6-b]quinazolinone derivatives were synthesized and characterized. Antiproliferation evaluation in vitro against four human cancer cell lines including SK-OV-3(ovarian cell), CNE-2(nasopharyngeal cell), MGC-803(gastric cell) and NCI-H460(lung cell) indicated that most of them exhibited potent anticancer activity and the IC50 value of the most potent compound lowered to sub-µM. DNA interaction assay indicated that compounds 4e, 4g, 6o, 6p, 8o can intercalate into DNA. Compounds 6 and 8 also demonstrated potent topoisomerase I (topo I) activity. Annexin V- FITC/propidium iodide dual staining assay and cell cycle analysis indicated that 2-(4-bromophenyl)-4-((3-(diethylamino)propyl)amino) -10H-pyridazino [1,6-b]quinazolin- 10-one (8p) could induce arrest cell cycle at G2 phase and apoptosis in MGC-803 cells in a dose-dependent manner. The in vivo antitumor efficiency of compound 8p was also evaluated on MGC-803 xenograft nude mice, and the relative tumor growth inhibition was up to 55.9% at a dose of 20 mg/kg per two days. The results suggested that pyridazino[1,6-b]-quinazolinones might serve as a promising novel scaffold for the development of new antitumor agents.

The N-terminus of MTRR plays a role in MTR reactivation cycle beyond electron transfer.

In eucaryotic cells, methionine synthase reductase (MSR/MTRR) is capable of dominating the folate-homocysteine metabolism as an irreplaceable partner in electron transfer for regeneration of methionine synthase. The N-terminus of MTRR containing a conserved domain of FMN_Red is closely concerned with the oxidation-reduction process. Maternal substitution of I22M in this domain can bring about pregnancy with high risk of spina bifida. A new variation of Arg2del was identified from a female conceiving a fetus with spina bifida cystica. Although the deletion is far from the N-terminal FMN_Red domain, the biochemical features of the variant had been seriously investigated. Curiously, the deletion of arginine(s) of MTRR could not affect the electron relay, if only the FMN_Red domain was intact, but by degrees reduced the ability to promote MTR catalysis in methionine formation. Confirmation of the interaction between the isolated MTRR N-terminal polypeptide and MTR suggested that the native MTRR N-terminus might play an extra role in MTR function. The tandem arginines at the end of MTRR N-terminus conferring high affinity to MTR were indispensable for stimulating methyltransferase activity perhaps via triggering allosteric effect that could be attenuated by removal of the arginine(s). It was concluded that MTRR could also propel MTR enzymatic reaction relying on the tandem arginines at N-terminus more than just only implicated in electron transfer in MTR reactivation cycle. Perturbance of the enzymatic cooperation due to the novel deletion could possibly invite spina bifida in clinics.

Characterization of the structural and molecular interactions of Ferulic acid ethyl ester with human serum albumin and Lysozyme through multi-methods.

Ferulic acid ethyl ester (FAEE) is an essential raw material for the formulation of drugs for cardiovascular and cerebrovascular diseases and leukopenia. It is also used as a fixed aroma agent for food production due to its high pharmacological activity. In this study, the interaction of FAEE with Human serum albumin (HSA) and Lysozyme (LZM) was characterized by multi-spectrum and molecular dynamics simulations at four different temperatures. Additionally, the quenching mechanism of FAEE-HSA and FAEE-LZM were explored. Meanwhile, the binding constants, binding sites, thermodynamic parameters, molecular dynamics, molecular docking binding energy, and the influence of metal ions in the system were evaluated. The results of Synchronous fluorescence spectroscopy, UV-vis spectroscopy, CD, three-dimensional fluorescence spectrum, and resonance light scattering showed that the microenvironment of HSA and LZM and the protein conformation changed in the presence of FAEE. Furthermore, the effects of some common metal ions on the binding constants of FAEE-HSA and FAEE-LZM were investigated. Overall, the experimental results provide a theoretical basis for promoting the application of FAEE in the cosmetics, food, and pharmaceutical industries and significant guidance for food safety, drug design, and development.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Qualitative Research on the Training Experiences and Needs of Intensive Care Unit General Nurses Against the Background of Regular Coronavirus Disease 2019 Prevention and Control.

Objective: This study aimed to investigate the training experiences and needs of intensive care unit (ICU) general nurses against a background of regular Coronavirus disease (COVID-19) prevention and control. Methods: Using the phenomenological method of qualitative research, semi-structured interviews were conducted with 10 ICU nurses. The interview data were analyzed, sorted, summarized, and refined using the content analysis method. Results: The following five themes were extracted from the interviews, based on the training experiences of the nurses: 1) broadening their thinking; 2) discovering their personal shortcomings; 3) gaining self-confidence; 4) calmly facing frontline work; 5) experiencing high assessment pressure. The training needs of the nurses could be summarized into the following four themes: 1) increased training time; 2) improving the assessment mechanism; 3) establishing a normal rotating-shift training system; 4) balancing the teaching levels. Conclusion: Against a background of regular epidemic prevention and control, ICU training for general nurses is of high practical significance and value. Thus, active exploration and research should be conducted to establish perfect training and assessment mechanisms for these nurses. Additionally, training methods that are suitable for clinical needs should be formulated and training systematization and standardization must be promoted.

Impact of intravenous dexmedetomidine on postoperative bowel movement recovery after laparoscopic nephrectomy: A consort-prospective, randomized, controlled trial.

BACKGROUND: Postoperative ileus is a frequent postoperative complication, especially after abdominal surgery. Sympathetic excitation is the primary factor for postoperative ileus. Sympathetic activation becomes increased by surgical stress, postoperative pain, and inflammation. Dexmedetomidine (DEX) can inhibit sympathetic nerve activity, inflammation, and pain. AIM: To observe whether DEX promotes bowel movements in patients after laparoscopic nephrectomy. METHODS: One hundred and twenty patients undergoing laparoscopic nephrectomy were assigned to three groups: C (normal saline infusion), D1 (DEX 0.02 µg/kg/h), and D2 (DEX 0.04 µg/kg/h). The primary outcomes were the recorded times to first flatus, defecation, and eating after surgery. The secondary outcomes were postoperative pain, assessed using the numerical rating scale (NRS), adverse effects, and the duration of the postoperative hospital stay. RESULTS: The times to first flatus, defecation, and eating in groups D1 and D2 were significantly shorter than those in group C (P < 0.01). The NRS scores at 8 h and 24 h after surgery were significantly lower in groups D1 and D2 than in group C (P < 0.05). No adverse effects were observed (P > 0.05). CONCLUSION: Postoperative infusion of DEX at 0.04 µg/kg/h facilitates bowel movements in patients undergoing laparoscopic nephrectomy.

Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging.

Acupuncture can reduce cognitive deficits in Alzheimer's disease. However, whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood. Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline. Therefore, we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications. A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks. Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration. Preventive electroacupuncture alleviated memory impairment, decreased tau hyperphosphorylation, and reduced glycogen synthase kinase-3ß protein and mRNA expression levels in the brainstem dorsal raphe nucleus, where intracellular neurofibrillary tangle lesions first occur. In addition, the DNA methylation level in the promoter region of the glycogen synthase kinase-3ß gene was increased. The effects of preventive electroacupuncture were stronger than those of preventive acupuncture. Intraperitoneal injection of 0.4 mg/kg 5-aza-2'-deoxycytidine, an inhibitor of DNA methyltransferase that blocks epigenetic modifications, antagonized the effects of preventive electroacupuncture. Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3ß gene in the dorsal raphe nucleus. This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine, China (approval No. HUCMS201712001) on November 28, 2017.

Molecular cloning and expression of a new gene, GON-SJTU1 in the rat testis.

BACKGROUND: Spermatogenesis is a complex process involving cell development, differentiation and apoptosis. This process is governed by a series of genes whose expressions are highly regulated. Male infertility can be attributed to multiple genetic defects or alterations that are related to spermatogenesis. The discovery, cloning and further functional study of genes related to spermatogenesis is of great importance to the elucidation of the molecular mechanism of spermatogenesis. It is also physiologically and pathologically significant to the therapy of male infertility. METHODS: GON-SJTU1 was identified and cloned from rat testis by cDNA library screening and 3'-and 5'-RACE. The products of GON-SJTU1 were assessed by Northern and Western blotting. The expression of GON-SJTU1 was also examined by In situ hybridization and immunohistochemistry. RESULTS: Here we identified and cloned a new gene, GON-SJTU1, with the biological process of spermatogenesis. GON-SJTU1 is highly expressed in the testis from day 1 to 15 and then decreased, suggesting that GON-SJTU1 might be a time-related gene and involved in the early stage of spermatogenesis. And the expression of GON-SJTU1 in the testis occurred in some male germ cells, particularly in gonocytes and spermatogonial stem cells. CONCLUSION: GON-SJTU1 may play a role in the biological process of spermatogenesis.

[Antiviral activities of cycloheximide and its derivatives].

Cycloheximide (CHX) inhibits protein synthesis in most eukaryotic cells and it is a well-known tool commonly used in biochemical research. In this paper, the antiviral spectrum of CHX against several DNA and RNA viruses have been evaluated. CHX showed strong inhibitory activities against several RNA viruses such as HIV-1, influenza viruses, coxsackie B virus, enterovirus (EV71) and several DNA viruses such as HSV and HCMV. Especially the strong inhibitory activities of CHX against coxsackie B virus and enterovirus caught our attention, since effective drugs available in clinic are limited. The SAR of CHX derivatives also has been discussed in the paper. The hydroxyl group at C-2' and carbonyl group at C-2" of CHX are essential for its antiviral activity. And modification to these groups results its derivatives' antiviral activities reduced or lost.

Experimental Evidence of the Benefits of Acupuncture for Alzheimer's Disease: An Updated Review.

As the global population ages, the prevalence of Alzheimer's disease (AD), the most common form of dementia, is also increasing. At present, there are no widely recognized drugs able to ameliorate the cognitive dysfunction caused by AD. The failure of several promising clinical trials in recent years has highlighted the urgent need for novel strategies to both prevent and treat AD. Notably, a growing body of literature supports the efficacy of acupuncture for AD. In this review, we summarize the previously reported mechanisms of acupuncture's beneficial effects in AD, including the ability of acupuncture to modulate Aß metabolism, tau phosphorylation, neurotransmitters, neurogenesis, synapse and neuron function, autophagy, neuronal apoptosis, neuroinflammation, cerebral glucose metabolism, and brain responses. Taken together, these findings suggest that acupuncture provides therapeutic effects for AD.

The MELD scoring system for predicting prognosis in patients with severe hepatitis after plasma exchange treatment.

BACKGROUND: Hepatic failure caused by severe hepatitis is a clinical syndrome where the major liver functions, particularly detoxification, synthetic functions, and metabolic regulation are impaired to different degrees, and may result in major life-threatening complications such as hepatic encephalopathy, ascites, jaundice, cholestasis, bleeding and hepatorenal syndrome. Plasma exchange (PE) has been found useful in treating patients with fulminant hepatic failure by removing hepatic toxins and replacement of clotting factors, so PE treatment has temporary supportive effects on liver failure caused by severe viral hepatitis. In this study, our aim was to predict the prognosis of patients with severe hepatitis after PE treatment using the end-stage liver disease (MELD) scoring system. METHODS: Two hundred and twenty patients were randomly divided into PE and control groups, and the MELD score was calculated for each patient according to the original formula. The efficacy of PE was assessed by mortality or improvement in biochemical parameters and MELD score. RESULTS: The levels of total bilirubin and international normalised ratio (INR) in patients whose MELD scores were between 30 and 39 were lower than those before PE treatment, as those in patients whose MELD scores were 40 or higher. The mortality of patients in the PE group with MELD scores from 30 to 39 was 50.0%, while it was 83.3% in the control group (P<0.01). The mortality of patients with MELD scores higher than 40 was 90.0% in the PE group and 98.0% in the control group (P>0.05). CONCLUSIONS: PE treatment can decrease the serum total bilirubin level and INR and MELD score of patients with severe hepatitis and improve liver function. Compared with the control group, PE can significantly decrease the mortality of patients with MELD scores from 30 to 39, but has no effect in patients with MELD scores of 40 or higher.

An Inframe Trinucleotide Deletion in MTRR Exon 1 is Associated with the Risk of Spina Bifida.

Maternal genetic variants of enzymes in folate-homocysteine metabolic network are significantly correlative with the risk of spina bifida. To survey the genetic causality, the genotypes of three women having spina bifida fetuses from two unrelated Chinese families were screened in candidate alleles. Polymerase chain reaction, capillary electrophoresis and Sanger sequencing were employed to recognize the allelic variation. A trinucleotide deletion (c.4_6delAGG) was identified in the first exon of MTRR. All the three women showed the novel clinical variation including one heterozygous and two homozygous. The siblings who had healthy babies from the same families did not harbor the variation. In the unaffected control individuals, the variant was also not observed. Eukaryotic expression and bioinformatics techniques were utilized to explore the molecular pathogenesis of the potential genetic risk of developing spina bifida. Exceptionally, the functional examination revealed that the Arg2del variant kept subcellular localization unaltered with catalytic activity intact, but failed to efficiently activate MTR compared with the wild type. Genetic disorder of folate and homocysteine metabolism during pregnancy is believed to be associated with folate-sensitive neural tube defects. The report highlights that the inframe deletion in MTRR exon 1 could be a high risk factor susceptibility to spina bifida.

[Clinical study of lymph node metastatic pattern of thoracic esophageal squamous carcinoma].

OBJECTIVE: To analyze the patterns of lymph node metastases of thoracic esophageal carcinoma and define the adequate range of lymph node dissection. METHODS: The clinical data of 217 patients with esophageal carcinoma undergoing radical surgical resection of the lymph nodes in three regions were retrospectively analyzed. RESULTS: Lymph node metastases were found in 136 of the 217 patients (62.6%) and skip metastases of the lymph nodes in 12 patients (5.5%). In 3 989 lymph nodes desected, metastases were identified in 454 lymph nodes (11.38%). The rates of lymph node metastasis were 31.7%, 21.2% and 12.1% in the neck, thoracic mediastinum and abdominal cavity, respectively, in upper thoracic esophageal carcinoma, 21.9%, 30.5% and 15.6% in middle thoracic carcinoma, and 9.75%, 12.7% and 34.5% in lower thoracic carcinoma. The degree of tumor differentiation, depth of tumor invasion and lymphatic vessel invasion were factors influencing lymph node metastases (P<0.05). CONCLUSION: Because of the upward, downward and skip metastasis of esophageal carcinoma cells to the lymph nodes, the operable patients with thoracic esophagus carcinoma should receive radical desection of the lymph nodes in the 3 regions to promote the patients' survival.

Molecular characterization of resistance, virulence and clonality in vancomycin-resistant Enterococcus faecium and Enterococcus faecalis: A hospital-based study in Beijing, China.

The incidence of vancomycin-resistant enterococcus (VRE) in China is increasing, the molecular epidemiology of VRE in China is only partly known. This study was conducted to assess the molecular characterization of resistance, virulence and clonality of 69 vancomycin-resistant Enterococcus faecium (VREfm) and seven vancomycin-resistant Enterococcus faecalis (VREfs) isolates obtained from a Chinese hospital between July 2011 and July 2013. The glycopeptide resistance genes (VanA and VanB) were screened by multiplex PCR. The presence of five putative virulence genes (esp, gelE, asa1, hyl and cylA) were evaluated by another multiplex PCR. Multilocus sequence typing (MLST) scheme was used to assess the clonality. All 76 VRE isolates exhibited VanA phenotype and harbored VanA gene. Esp was the only gene detected both in VREfm and VREfs strains, accounting for 89.9% and 42.9%, respectively. The hyl gene was merely positive in 27.5% of VREfm strains. MLST analysis demonstrated three STs (ST6, ST4 and ST470) in VREfs and twelve STs (ST78, ST571, ST17, ST564, ST389, ST18, ST547, ST341, ST414, ST343, ST262 and ST203) in VREfm, which were all designated as CC17 by eBURST algorithm. An outbreak of VREfm belonging to ST571 was found to happen within the neurology ward in this hospital. To our knowledge, this is the first report of ST6 (CC2) VREfs strains in China and the first outbreak report of VREfm strains belonging to ST571 around the world. Our data could offer important information for understanding the molecular features of VRE in China.

[Isolation and structure identification of flavonol glycoside from Lysimachia christinae Hance].

AIM: To isolate and prepare chemical standards. METHODS: Flavonol glycoside and rhamnonic acid gamma-lactone were isolated from whole plants of Lysimachia christinae Hance. with 95% ethanol and purified by silica gel column chromatography. UV, IR, MS, 1HNMR, 13CNMR, DEPT, HMQC, HMBC were used for the structural identification. RESULTS: Two compounds were obtained. They were identified as rhamnonic acid gamma-lactone (I) and kaempferol-3-O-alpha-L-rhamnosyl (1-->2)-beta-D-xyloside (II). CONCLUSION: Compound I was isolated from this genus for the first time. Compound II is a new compound named as lysimachiin.

[Laparoscopic choledochocele resection report of 48 cases].

OBJECTIVE: To summarize surgery experience and efficiency of laparoscopic excision of choledochal cyst and reconstruction of biliary tract and to analyze the treatments administered during intra and post-operation of the biliary reconstruction. METHODS: We enrolled 48 cases of video-guided laparoscopic intraoperative cholangiography, cholecystectomy, choledochocele resection, Roux-en-Y hepaticojejunostomy with an anti-reflux valve from August, 2001 to October, 2003. Their operative procedures and aims were retrospectively analyzed. RESULTS: Forty-four out of 48 patients successfully underwent laparoscopy and recovered soon. Only 4 cases were transformed to open operation. The post-operation complications were found in 4 cases. CONCLUSION: Video-guided laparoscopic excision of choledochal cyst, biliary tract reconstruction and Roux-en-Y hepaticojejunostomy are an effective method of treatment with advantages of minimal injury, less bleeding, and sooner recovery.

[Spinal fixed-point rotating reduction in treating lumbar disc herniation by three-dimensional MRI].

OBJECTIVE: To observe three-dimensional space position change of nucleus pulposus and nerve root before and after treatment of lumbar disc herniation by spinal fixed-point rotating reduction, and explore the mechanisms. METHODS: Totally 52 patients with L5S1 lumbar disc hernation treated by spinal fixed-point rotating reduction were collected from April 2009 to June 2011. There were 33 males and 19 females with an average age of 34.6 years old (ranged, 19 to 55). Three-dimensional MRI were performed to observe relationship between nucleus pulposus and related nerve root,configuration change of spine and pelvic on coronary MRI. RESULTS: MRI showed relationship between nucleus pulposus and related nerve root mainly located on axillary, shoulder, front and surround. Vertebral displacement disappeared, lumbocrural pain alleviated after manipulative therapy. All patients were followed up from 2 to 28 months with an average of 12 months, and no recurred. All patients recovered work. Nucleus pulposus had no change,while lumbral spinal and pelvic curve changed before and after admission. CONCLUSION: Lumbar disc herniation combined with single (multiple) vertebral displacement,can cause biomechanical properties of nucleus puplosus and related nerve root, while spinal fixed-point rotating reduction can correct vertebral displacement, recover balance between inside and outside of spinal.