Acute ischemic stroke in tuberculous meningitis.

Background: The underlying mechanism for stroke in patients with tuberculous meningitis (TBM) remains unclear. This study aimed to investigate the predictors of acute ischemic stroke (AIS) in TBM and whether AIS mediates the relationship between inflammation markers and functional disability. Methods: TBM patients admitted to five hospitals between January 2011 and December 2021 were consecutively observed. Generalized linear mixed model and subgroup analyses were performed to investigate predictors of AIS in patients with and without vascular risk factors (VAFs). Mediation analyses were performed to explore the potential causal chain in which AIS may mediate the relationship between neuroimaging markers of inflammation and 90-day functional outcomes. Results: A total of 1,353 patients with TBM were included. The percentage rate of AIS within 30 days after admission was 20.4 (95% CI, 18.2-22.6). A multivariate analysis suggested that age ≥35 years (OR = 1.49; 95% CI, 1.06-2.09; P = 0.019), hypertension (OR = 3.56; 95% CI, 2.42-5.24; P < 0.001), diabetes (OR = 1.78; 95% CI, 1.11-2.86; P = 0.016), smoking (OR = 2.88; 95% CI, 1.68-4.95; P < 0.001), definite TBM (OR = 0.19; 95% CI, 0.06-0.42; P < 0.001), disease severity (OR = 2.11; 95% CI, 1.50-2.90; P = 0.056), meningeal enhancement (OR = 1.66; 95% CI, 1.19-2.31; P = 0.002), and hydrocephalus (OR = 2.98; 95% CI, 1.98-4.49; P < 0.001) were associated with AIS. Subgroup analyses indicated that disease severity (P for interaction = 0.003), tuberculoma (P for interaction = 0.008), and meningeal enhancement (P for interaction < 0.001) were significantly different in patients with and without VAFs. Mediation analyses revealed that the proportion of the association between neuroimaging markers of inflammation and functional disability mediated by AIS was 16.98% (95% CI, 7.82-35.12) for meningeal enhancement and 3.39% (95% CI, 1.22-6.91) for hydrocephalus. Conclusion: Neuroimaging markers of inflammation were predictors of AIS in TBM patients. AIS mediates < 20% of the association between inflammation and the functional outcome at 90 days. More attention should be paid to clinical therapies targeting inflammation and hydrocephalus to directly improve functional outcomes.

Diagnostic Accuracy of CT-Guided Percutaneous Pulmonary Biopsy for Distinguishing Benign and Malignant Solitary Pulmonary Nodules.

Background: Isolated pulmonary nodules (SPNs) are small, circular lesions within lung tissue, often challenging to diagnose due to their size and lack of typical imaging features. Timely diagnosis is crucial for treatment decisions. However, the difficulty in qualitative diagnosis necessitates clinical biopsies. Objective: This study aimed to assess the diagnostic accuracy of CT-guided percutaneous lung biopsy for SPNs and identify potential risk factors for malignancy. Methods: We conducted a retrospective analysis of 112 patients with SPNs who underwent CT-guided core needle biopsy (CT-CNB) between June 2020 and June 2022. Histological and cytological results were obtained for all patients, and clinical data and imaging characteristics were compared between benign and malignant SPN groups. Binary logistic regression was used to analyze risk factors for malignancy, and complications were observed. Results: Cytological and histological specimens were successfully obtained for all patients. The cohort consisted of 43 patients with benign SPNs and 69 with malignant SPNs. Among the malignant SPN group, 67 cases were confirmed via CT-CNB and 2 through surgery, resulting in a sensitivity of 97.10% and specificity of 100.00%. The malignant nodules comprised 45 adenocarcinomas, 14 squamous cell carcinomas, 8 metastatic tumors, and 2 small cell carcinomas. Notably, 2 initially diagnosed as malignant cases were found to have chronic inflammation on preoperative biopsy but revealed adenocarcinoma and squamous cell carcinoma post-surgery. The benign nodules encompassed 20 granulomatous inflammation cases, 15 chronic inflammation, 3 fungal granulomas, 2 hamartomas, and 1 fibrous tissue. Cytological smears exhibited a sensitivity of 81.3% and a specificity of 100.0% for malignancy. Significantly, age ≥60, elevated tumor markers, and specific imaging signs (burr, foliation, pleural pull) were identified as risk factors for malignant SPNs using Binary Logistic regression (all P < .05). Conclusions: CT-guided percutaneous lung biopsy demonstrates excellent diagnostic efficacy and safety for distinguishing benign and malignant SPNs.

Methylation-associated silencing of miR-9-1 promotes nasopharyngeal carcinoma progression and glycolysis via HK2.

Characteristically, cancer cells metabolize glucose through aerobic glycolysis, known as the Warburg effect. Accumulating evidence suggest that during cancer formation, microRNAs (miRNAs) could regulate such metabolic reprogramming. In the present study, miR-9-1 was identified as significantly hypermethylated in nasopharyngeal carcinoma (NPC) cell lines and clinical tissues. Ectopic expression of miR-9-1 inhibited NPC cell growth and glycolytic metabolism, including reduced glycolysis, by reducing lactate production, glucose uptake, cellular glucose-6-phosphate levels, and ATP generation in vitro and tumor proliferation in vivo. HK2 (encoding hexokinase 2) was identified as a direct target of miR-9-1 using luciferase reporter assays and Western blotting. In NPC cells, hypermethylation regulates miR-9-1 expression and inhibits HK2 translation by directly targeting its 3' untranslated region. MiR-9-1 overexpression markedly reduced HK2 protein levels. Restoration of HK2 expression attenuated the inhibitory effect of miR-9-1 on NPC cell proliferation and glycolysis. Fluorescence in situ hybridization results indicated that miR-9-1 expression was an independent prognostic factor in NPC. Our findings revealed the role of the miR-9-1/HK2 axis in the metabolic reprogramming of NPC, providing a potential therapeutic strategy for NPC.

Network pharmacology unveils spleen-fortifying effect of Codonopsis Radix on different gastric diseases based on theory of "same treatment for different diseases" in traditional Chinese medicine.

Objective: "Same treatment for different diseases" is a unique treatment strategy under the guidance of traditional Chinese medicine (TCM) theory. Codonopsis Radix (Codonopsis pilosula, Dangshen in Chinese) with spleen-fortifying effect was employed to understand the strategy of "Same treatment for different diseases", based on its common mechanism in the treatment of gastric diseases including gastric ulcer, gastritis and gastric cancer via network pharmacology research. Methods: Network pharmacology research methods were used to analyze the interaction network and potential mechanisms of Dangshen in treating gastric ulcer, gastritis and gastric cancer. The active components and their target proteins of Dangshen were integrated from TCMSP, BATMAN-TCM databases. The targets of gastric ulcer, gastritis and gastric cancer were collected through GeneCards, PubMed, TDD and DisGeNET Database. Through screening, the key components and the key targets of Dangshen in treating gastric ulcer, gastritis and gastric cancer were obtained. After KEGG pathway analysis and GO analysis, the important pathways and biological processes were analyzed. Results: Through data and literature mining, the common and specific pharmaceutical effects and mechanism of Dangshen were summarized in these three gastric lesions. It was shown that Dangshen mainly acted on gastric ulcer, gastritis and gastric cancer through the overall regulation of the PI3K-AKT signaling pathway. With the development of the disease, it will gradually increase the control of inflammation through TNF, NF-κB and other inflammation-related signaling pathways to reduce inflammatory damage. For tumorigenesis, it pays more attention to inhibiting the ErbB signaling pathways to reduce the proliferation and migration of tumor cells. In addition, Dangshen's regulation of HIF-1 signaling pathway may also be beneficial for the treatment of gastric ulcer, gastritis and gastric cancer. Conclusion: Dangshen achieves spleen-fortifying effect on gastric diseases including gastric ulcer, gastritis and gastric cancer through multiple targets in multiple pathways, especially PI3K-AKT pathway and HIF-1 pathway. It could provide a scientific basis for understanding the strategy of "Same treatment for different diseases" in traditional Chinese medicine.

Common mechanism of Citrus Grandis Exocarpium in treatment of chronic obstructive pulmonary disease and lung cancer.

Objective: "Same treatment for different diseases" is a unique treatment strategy in traditional Chinese medicine. Two kinds of malignant respiratory diseases endanger human health-chronic obstructive pulmonary disease (COPD) and lung cancer. Citrus Grandis Exocarpium (Huajuhong in Chinese, HJH), a famous herbal, is always applied by Chinese medicine practitioners to dispersion the lung to resolve phlegm based on "syndrome differentiation and treatment" theory. However, the common mechanism for HJH's treatment of COPD and lung cancer is not clear. Methods: In this study, based on network pharmacology and molecular docking technology, the common mechanism of HJH in the treatment of COPD and lung cancer was studied. The active ingredients and related targets of HJH were integrated from TCMSP, BATMAN-TAM, STP, and Pubchem databases. The standard names of these targets were united by UniProt database. Targets of COPD and lung cancer were enriched through GeneCards, NCBI (Gene), Therapeutic Target Database, and DisGeNET (v7.0) databases. Then the intersection targets of HJH and diseases were obtained. The STRING network and the Cytoscape 3.7.2 were used to construct PPI network, the DAVID database was used to perform GO and KEGG analysis. Then Cytoscape 3.6.1 was used to build "ingredient-target-signal pathway" network. Finally, AutoDock 1.5.6 software was used to perform molecular docking of key proteins and molecules. Results: Eleven active ingredients in HJH were obtained by searching the database, corresponding to 184 HJH-COPD-lung cancer targets intersection. The results of biological network analysis showed that naringenin, the active component in HJH, could mainly act on target proteins such as AKT1, EGFR. Then through positive regulation of vasoconstriction and other biological processes, naringenin could regulate estrogen signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway to play an important role in the treatment of both COPD and lung cancer. Conclusion: Network pharmacology was employed to systematically investigate the active ingredients and targets of HJH in treatment of COPD and lung cancer. And then, the common pharmacodynamic network of HJH for the two malignant respiratory diseases was firstly described. Furthermore, naringenin was proved to strongly bind with AKT1 and EGFR. It may provide the scientific basis for understanding the "Same treatment for different diseases" strategy in traditional Chinese medicine and inspirit subsequent drug discovery for COPD, lung cancer and other malignant lung diseases.

Layer-by-layer nanoparticles co-loading gemcitabine and platinum (IV) prodrugs for synergistic combination therapy of lung cancer.

PURPOSE: Cisplatin plus gemcitabine (GEM) is a standard regimen for the first-line treatment of advanced non-small cell lung cancer. The aim of this study was to prepare biocompatible and biodegradable polymeric prodrugs and construct nanoparticles (NPs) with layer-by-layer (LbL) technique. METHODS: Platinum (Pt) (IV) complex with a carboxyl group was conjugated to the amino group of chitosan (CH), resulting in a CH-Pt conjugation with positive charge. GEM with amino group was conjugated to the carboxyl group of hyaluronic acid (HA), resulting in a HA-GEM conjugation with negative charge. Novel LbL NPs consisting of the CH-Pt core and the HA-GEM layer, named as HA-GEM/CH-Pt NPs, were constructed. The physicochemical properties of the HA-GEM/CH-Pt NPs were investigated. In vitro cytotoxicity against human non-small lung cancer cells (NCl-H460 cells) was investigated, and in vivo antitumor efficiency was evaluated on mice bearing NCl-H460 cells xenografts. RESULTS: HA-GEM/CH-Pt NPs have a size of about 187 nm, a zeta potential value of -21 mV and high drug encapsulation efficiency of 90%. The drug release of HA-GEM/CH-Pt NPs exhibited a sustained behavior. HA-GEM/CH-Pt NPs could significantly enhance in vitro cytotoxicity and in vivo antitumor effect against lung cancer animal model compared to the single-drug-loaded NPs and free drug solutions. CONCLUSION: The results demonstrated that the HA-GEM/CH-Pt NPs might be a promising system for the synergetic treatment of lung carcinoma.

[A project to improve the "do not resuscitation" consent completeness rate for terminal cancer patients].

BACKGROUND: Signed do-not-resuscitate (DNR) consent is the essential first step for terminal cancer patients to choose palliative care and a quality marker of terminal care. DNR consent completeness helps deliver correct information, ensure consent legal validity, reduce medical disputes, and protect patient and family rights. The DNR consent completeness rate during May and June 2005 was only 33.9% in our hospital. Reasons indicated for this low rate included: (1) lack of a standard operating procedure for DNR consent; (2) multiple DNR consent versions; (3) lack of DNR-related education; and (4) lack of monitoring procedures. Our team developed a project to resolve these problems and improve terminal care quality. PURPOSE: The goal of this project was to increase the rate of DNR consent completeness from 33.9% to 80%. RESOLUTION: The plan, implemented between August and December 2009, included the following components: (1) establish standard guidelines for DNR consent; (2) simplify and unify DNR consent procedures; (3) provide DNR education for hospital staff; and (4) establish a DNR consent monitoring system. RESULTS: The DNR consent completeness rate rose from 33.9% to 90%. The goal of this project was thus achieved. CONCLUSION: This project effectively improved the DNR consent completeness rate at our hospital. The project ensured patients a good death and enhanced terminal care quality and patient satisfaction. Our experience may provide a reference to help other hospitals increase DNR their consent completeness rates.

Improved proteomic analysis pipeline for LC-ETD-MS/MS using charge enhancing methods.

Electron transfer dissociation (ETD) is a useful and complementary activation method for peptide fragmentation in mass spectrometry. However, ETD spectra typically receive a relatively low score in the identifications of 2+ ions. To overcome this challenge, we, for the first time, systematically interrogated the benefits of combining ion charge enhancing methods (dimethylation, guanidination, m-nitrobenzyl alcohol (m-NBA) or Lys-C digestion) and differential search algorithms (Mascot, Sequest, OMSSA, pFind and X!Tandem). A simple sample (BSA) and a complex sample (AMJ2 cell lysate) were selected in benchmark tests. Clearly distinct outcomes were observed through different experimental protocol. In the analysis of AMJ2 cell lines, X!Tandem and pFind revealed 92.65% of identified spectra; m-NBA adduction led to a 5-10% increase in average charge state and the most significant increase in the number of successful identifications, and Lys-C treatment generated peptides carrying mostly triple charges. Based on the complementary identification results, we suggest that a combination of m-NBA and Lys-C strategies accompanied by X!Tandem and pFind can greatly improve ETD identification.

Mercury contamination and accumulation in sediments of the East China Sea.

Mercury (Hg) concentrations in sediment samples collected from the inner and middle shelves of the East China Sea (ECS) were analyzed to evaluate Hg contamination levels and to calculate Hg sedimentation rates and total accumulation in the ECS. The range of Hg concentrations in surface sediments of the inner shelf was 26.5-47.6 ng/g, and that for the middle shelf was 4.1-13.9 ng/g. Hg concentrations correlated well with organic carbon contents but varied inversely with sediment grain size. Enrichment factors indicated that the whole inner shelf and a small portion of the middle shelf were slightly contaminated by Hg. Hg accumulation rates in the ECS ranged between 0.42-48.7 ng/(cm2 x yr), with higher values observed in the inner shelf. Total Hg accumulation in the calculated area (accounting for 80% of the ECS continental shelf area) ranged from 25 to 30 tons/yr; approximately 51% and 17% of the accumulated Hg mass was deposited in the Yangtze estuarine zone and the inner shelf, respectively.

Biotin tagging coupled with amino acid-coded mass tagging for efficient and precise screening of interaction proteome in mammalian cells.

In mammalian cells, when tandem affinity purification approach is employed, the existence of untagged endogenous target protein and repetitive washing steps together result in overall low yield of purified/stable complexes and the loss of weakly and transiently interacting partners of biological significance. To avoid the trade-offs involving in methodological sensitivity, precision, and throughput, here we introduce an integrated method, biotin tagging coupled with amino acid-coded mass tagging, for highly sensitive and accurate screening of mammalian protein-protein interactions. Without the need of establishing a stable cell line, using a short peptide tag which could be specifically biotinylated in vivo, the biotin-tagged target/bait protein was then isolated along with its associates efficiently by streptavidin magnetic microbeads in a single step. In a pulled-down complex amino acid-coded mass tagging serves as "in-spectra" quantitative markers to distinguish those bait-specific interactors from non-specific background proteins under stringent criteria. Applying this biotin tagging coupled with amino acid-coded mass tagging approach, we first biotin-tagged in vivo a multi-functional protein family member, 14-3-3epsilon, which was expressed at close to endogenous level. Starting with approximately 20 millions of 293T cells which were significantly less than what needed for a tandem affinity purification run, 266 specific interactors of 14-3-3epsilon were identified in high confidence.

[The observe of clinical effect of treating lumbar intervertebral disc herniation by bone setting manipulation of different directions].

OBJECTIVE: To compare the effect between lumbar backwards flexion manipulation and rotating manipulation for treating lumbar intervertebral disc herniation. METHODS: Two hundred and nine patients of lumbar intervertebral disc herniation, male 131, female 78, the age from 20 to 79 years old, 58 cases of all these patients age above 50. According to diagnosis the ladder of the 92 cases bulging type, 69 hernia type, 48 cases free type. The patients were randomly divided into treatment group (107 cases) and control group (102 cases). All the patients were treated with the three-dimensional computer-controlled traction therapeutic apparatus, with continued traction for 30 minutes. After traction, lumbar backwards flexion manipulation and rotating manipulation were respectively adopted in treatment group and control group (on alternate days one time, 3 times as a course of treatment). The symptoms and signs (including back pain and discomfort, lower limb pain and numbness, powerless urination and defecation, numbness in perineum, straight-leg raising degree, ability of lower extremity walking, work and live) of patients were observed after treatment. RESULTS: All the patients were followed up from 1 to 6 months with an average of 3.2 months. After treatment, the symptoms and signs of patients have markedly improved (P < 0.01), but the lower back pain and discomfort, lower limb walking ability in treatment group were better than control group (P < 0.05). According therapeutic criteria, the effect of treatment group was better than of control group (P < 0.01). In cases with bulging type, 47 in treatment group and 45 in control group, the effect of treatment group was better than of control group (P < 0.05); in cases with hernia type, 35 in treatment group and 34 in control group, there was no significantly difference in effect between two groups (P > 0.05); in cases of free type, 25 in treatment group and 23 in control group, there was no significantly difference in effect between two groups (P > 0.05). CONCLUSION: The global effect of lumbar backwards flexion manipulation was satisfactory than rotating manipulation for treating lumbar intervertebral disc herniation. But rotating manipulation suited to free type.

[Design and synthesis of a type of benzopyran derivatives with insulin-sensitizing activity].

Ten novel compounds were designed and synthesized on the basis of compound 1, their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Results showed that compound 10 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, which indicated that compound 10 may possess well insulin-sensitizing activity.

[Design, synthesis and anti-HBV activity of L-amino acid ester prodrugs of acyclic nucleoside phosphonates].

To design and synthesis a series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates with more potent anti-HBV activity, adefovir dipivoxil was used as lead compound, according to the results of enhanced oral bioavailability and antiviral activities of nucleoside L-amino acid ester prodrugs. Eleven novel L-amino acid ester prodrugs of acyclic nucleoside phosphonates were designed and synthesized, their anti-HBV activities were evaluated in HepG2 2.2.15 cells. Eight compounds exhibited antiviral activity, and compound 11 showed the most potent anti-HBV activity and highest selective index in vitro (EC50 0.0952 micromol x L(-1), SI 69523). Moreover, by analyzing the primary structure and activity relationship of these compounds, it could be suggested that L-amino acid ester strategy has significant potential in the acyclic nucleoside phosphonates prodrug design.

[Synthesis and biological activity of a series of benzopyran derivatives].

Thirteen benzopyran derivatives were synthesized and their activity stimulating the differentiation of preadipocytes into adipocytes were evaluated with 3T3-L1 cells. Compound 8 was also tested for its hypoglycemic activity on db diabetes mice model. Results indicated that compounds 3, 8 and 11 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, and compound 8 can reduce the blood-sugar level of db diabetes mice dramatically.

Insulin-sensitizing effects of a novel alpha-methyl- alpha -phenoxylpropionate derivative in vitro.

AIM: To examine the insulin sensitizing effects of a novel alpha-methyl-alpha- phenoxylpropionate derivative YY20 in insulin-sensitive cell lines. METHODS: The peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist bioactivities of YY20 were detected by a preadipocyte differentiation assay. RT-PCR and Western blotting analysis were used to detect the expression of the target gene or protein. The effects of YY20 on insulin-mediated glucose consumption were determined in the HepG2 human hepatocellular carcinoma line. RESULTS: YY20 could enhance the differentiation of preadipocytes to adipocytes and upregulate the gene expression of PPAR gamma 2, as well as the protein expression of insulin receptor substrate- 1 (IRS-1), glucose transporter-4 (GLUT4), and adiponectin (ACRP30). The effects on GLUT4 and ACRP30 could be reversed by the PPAR gamma inhibitor SR-202. Furthermore, YY20 efficiently reduced glucose consumptions in HepG2 cells after 24 h culture, and the effects were related to insulin and YY20 concentrations. CONCLUSION: YY20, a potential insulin-sensitizing agent like rosiglitazone, could enhance glucose consumption in HepG2 cells in a concentration- and insulindependent manner. It may improve the insulin resistance associated with type 2 diabetes.

[Design, synthesis and insulin-sensitizing activity of indole derivatives].

AIM: To design and synthesize compounds with insulin-sensitizing activity. METHODS: Using association principle of drug design, ten title compounds were designed and synthesized on the basis of known compounds with insulin-sensitizing activity, and their insulin-sensitizing activity were evaluated on 3T3-L1 pre-adipocyte cells. RESULTS: One of the synthesized compounds showed strong insulin-sensitizing activity in vitro. CONCLUSION: This compound may possess good sugar-lowering activity, and will be chosen for further hypoglycemic evaluation in vivo.

[Preliminary study on the improvement of wound microcirculation and retrospection on several methods of the management of deep partial thickness burn wound].

OBJECTIVE: To analyze several methods of wound repair for deep partial thickness burn wounds retrospectively, so as to evaluate the significance of improvement of wound microcirculation on wound healing. METHODS: (1) 2,976 burn patients admitted to our department were enrolled in the study, among them 614 undertook tangential excision, 32, eschar abrasion, 86 allo-skin coverage after debridement, 1836 tropical application of silver sulfadiazine and 408 with traditional Chinese medicine (Jing Wan Hong ointment) with gauze bandage. The results of the management with different methods were compared. (2) Rat model with deep partial thickness burn was reproduced and topical application of silver sulfadiazine was given. The rats were randomly divided into control (n = 10, with normal saline injected via caudal vein within 5 minutes postburn), and treatment (n = 10, with batroxobin injected via caudal vein within 5 minutes postburn) groups. The blood flow perfusion unit in the wound skin was measured before burn and at 0.5 to 72 postburn hours by Laser Doppler. The wound healing rate, contraction rate and wound healing time in each group were calculated on 14 and 18 postburn days (PBDs). The number of hair follicles after wound healing was observed by histological method. RESULTS: (1) The burn wound treated by tangential excision healed within 2 to 3 post operation weeks (POWs), with the healing rate of 94.8% in patients with burn covering 50% - 70% TBSA and 93.4% in those with burn of 80% approximately 98% TBSA. The healing time of patients with allo-grafts coverage after eschar abrasion was 13.8 +/- 2.1 days without scar formation. The wound healing time was 18.0 +/- 2.3 day in 82 patients with allo-graft coverage after debridement, and it was 26.0 +/- 3.2 days with subeschar healing in 1658 patients with topical application of silver sulfadiazine. Infection in burn wound was encountered in most patients undergoing traditional Chinese medicine bandage treatment with wound healing time of 26.0 +/- 2.8 days in the lower extremities. (2) The blood flow perfusion unit of the rats in the treatment group was significantly higher than that in the control group (P < 0.01). The wound healing rate in treatment group on 14 and 18 PBD was obviously higher than that in the control group (P < 0.01). But the wound contraction rate in the two groups was similar (P > 0.05). The wound healing time in treatment group was much shorter than that in control group (P < 0.01). A few hair follicles remained in the dermis of the rats in the control group on 30 PBD, and the number was evidently smaller than that in the treatment group (P < 0.01). CONCLUSION: Early tangential excision and eschar abrasion remained better methods in the management of deep partial thickness burn wounds, as they could ameliorate burn wound infection, shorten treatment period, raise wound healing rate and quality. Application of batroxobin could accelerate wound healing rate by improving wound microcirculation in deep partial thickness burn wound.

A density-functional study of the mechanism for the diastereoselective epoxidation of chiral allylic alcohols by the titanium peroxy complexes.

The epoxidation of three stereolabeled methyl-substituted chiral allylic alcohols with (1,2)A and/or (1,3)A allylic strain, namely 3-methylbut-3-en-2-ol (1a), pent-3-en-2-ol (1b), and 3-methylpent-3-en-2-ol (1c), have been studied by the density-functional theory method, B3LYP/6-31+G(d,p). For each substrate we calculated the two prereaction complexes with Ti(OH)(4)/MeOOH (the oxidant model for Ti(O-i-Pr)(4)/t-BuOOH), their threo and erythro transition states for oxygen transfer, and the corresponding product complexes. For substrate 1a, the erythro transition state is 0.91 kcal/mol of lower energy than the threo one; for substrates 1b and 1c, the threo compared to the erythro transition states are by 1.05 and 0.21 kcal/mol more favorable, respectively. The threo/erythro product ratios have been estimated from the computed free energies for the competing threo and erythro transition states 3a-c in CH(2)Cl(2) solution to be 12:88 (1a), 92:8 (1b), and 77:23 (1c), which are in good accordance with the experimental values 22:78 (1a), 91:9 (1b), and 83:17 (1c). The diastereoselectivity of this diastereoselective oxyfunctionalization is rationalized in terms of the competition between (1,3)A and (1,2)A strain and the electronic advantage for the spiro transition state. In addition, solvent effects are also play a role for the diastereoselectivity at the same time.