Serum sphingolipids aid in diagnosing adult HIV-negative patients with pulmonary cryptococcosis: a clinical cohort study.

Background: Pulmonary cryptococcosis (PC) contributes to the ongoing global disease burden in human immunodeficiency virus (HIV)-negative populations. Since some PC patients are misdiagnosed under existing diagnostic guidelines, new diagnostic markers are needed to improve diagnostic accuracy and therapeutic efficacy and reduce disease risk. Methods: Our previously established sphingolipidomic approach was employed to explore the use of serum sphingolipids (SPLs) in diagnosing HIV-negative patients with PC. A clinical cohort of PC, pulmonary aspergillosis (PA), and tuberculosis (TB) patients and healthy controls was assessed to identify SPL biomarkers. Results: A total of 47 PC, 27 PA, and 18 TB patients and 40 controls were enrolled. PC and TB patients had similar clinical features, laboratory test results and radiological features, excluding plural effusion. The serum ceramide [Cer (d18:1/18:0)] level showed a significant increase in PC patients compared to controls and PA and TB patients (P<0.05). Cer (d18:1/18:0) was identified as a specific diagnostic biomarker for PC. The optimal cut-off value of greater than 18.00 nM showed a diagnostic sensitivity of 76.60% and a specificity of 95.00% and better distinguished PC patients from PA and TB patients. Furthermore, the serum Cer (d18:1/18:0) level gradually decreased after 3 and 6 months of treatment, suggesting the prediction potential for therapeutic efficacy of this biomarker. In addition, Cer (d18:1/18:0) analysis presented a higher sensitivity than the cryptococcal antigen (CrAg) assay. Conclusions: This is the first study to report the use of the SPL Cer (d18:1/18:0) as a serum biomarker for diagnosing Cryptococcus spp. infection in HIV-negative patients.

The association between heavy metal exposure and erectile dysfunction in the United States / 亚洲男科学杂志(英文版)

Literature regarding the impacts of heavy metal exposure on erectile dysfunction (ED) is scarce. We aimed to evaluate the correlation between 10 urinary metals and ED in a large, nationally representative adult male sample. The dataset was extracted from the National Health and Nutrition Examination Survey (NHANES) during the period of 2001-2002 and 2003-2004. Weighted proportions and multivariable logistic regression analysis adjusted for confounding variables were utilized to determine the relationship between metal exposure and ED. Weighted quantile sum (WQS) regression was utilized to evaluate the impact of a mixture of urinary metals on ED. A total of 1328 participants were included in our study. In multivariable logistic regression analysis, cobalt (Co) and antimony (Sb) were positively associated with ED (odds ratio [OR]: 1.36, 95% confidence interval [CI]: 1.10-1.73, P = 0.020; and OR: 1.41, 95% CI: 1.12-1.77, P = 0.018, respectively) after full adjustment. Men in tertile 4 for Co (OR: 1.49, 95% CI: 1.02-2.41, P for trend = 0.012) and Sb (OR: 1.53, 95% CI: 1.08-2.40, P for trend = 0.041) had significantly higher odds of ED than those in tertile 1. Furthermore, the WQS index was significantly linked with increased odds of ED after full adjustment (OR: 1.31, 95% CI: 1.04-1.72, P < 0.05). Our study expanded on previous literature indicating the possible role of heavy metal exposure in the etiology of ED. The evaluation of heavy metal exposure should be included in the risk assessment of ED.

Development of Small-Molecule Fluorescent Probes Targeting Enzymes.

As biological catalysts, enzymes are vital in controlling numerous metabolic reactions. The regulation of enzymes in living cells and the amount present are indicators of the metabolic status of cell, whether in normal condition or disease. The small-molecule fluorescent probes are of interest because of their high sensitivity and selectivity, as well as their potential for automated detection. Fluorescent probes have been useful in targeting particular enzymes of interest such as proteases and caspases. However, it is difficult to develop an ideal fluorescent probe for versatile purposes. In the future, the design and synthesis of enzyme-targeting fluorescent probes will focus more on improving the selectivity, sensitivity, penetration ability and to couple the fluorescent probes with other available imaging molecules/technologies.

[Research progress on chemical constituents and quality control methods of Succus Bambusae].

Through the investigation of a large number of both domestic and overseas literatures and related quality standards, chemical compositions, quality evaluation system and quality control methods of Succus Bambusae were systematic summarized in this study. There were abundant chemical constituents in Succus Bambusae, mainly including volatile ingredients, amino acids, flavonoids, trace elements and vitamins, with high medicinal and edible value. The quality control methods involved traditional morphological identification, spectroscopy, chromatography and other techniques. However, the current quality standards of Succus Bambusae are relatively low, lacking safety indicators, and cannot effectively ensure its quality, seriously affecting the safety and effectiveness of its clinical use. Therefore, it is particularly important to establish a set of highly sensitive and specific quality evaluation system for Succus Bambusae. In this paper, the current research status of the chemical compositions and quality standards of Succus Bambusae were reviewed, with the purpose of providing a basis for further improvement of its quality evaluation system.

Ethyl 2-(2,6-difluoro-benz-yloxy)-4-(4,6-dimethoxy-pyrimidin-2-yl)quinoline-3-carboxyl-ate.

In the title compound, C(25)H(21)F(2)N(3)O(5), the pyrimidine and difluoro-benz-yloxy rings are twisted away from the central quinoline ring system, making dihedral angles of 54.6 (1) and 74.1 (1)°, respectively. A weak C-H⋯O inter-action links symmetry-related mol-ecules, forming a pseudo-dimer. π-π inter-actions between the quinoline rings of symmetry-related mol-ecules [centroid-centroid distance = 3.5479 (10) Å] link these dimers into chains parallel to [101]. Weak C-H⋯π inter-actions join adjacent chains, forming a two-dimensional layer parallel to (101).

(RS)-(2-Bromo-4-fluoro-anilino)[2-(4,6-dimethoxy-pyrimidin-2-yl-oxy)phen-yl]acetonitrile.

In the title compound, C(20)H(16)BrFN(4)O(3), the pyrimidine and 2-bromo-4-fluoro-phenyl rings are twisted away from the central benzene ring, making dihedral angles of 77.7 (1) and 85.5 (1), respectively. A pair of C-H⋯F inter-actions is involved in an R(2) (2)(8) motif, linking the mol-ecules into dimers. These ring motifs are situated about the crystallographic centres of symmetry. C-H⋯O hydrogen bonds link the dimers into chains running parallel to [11]. Additionally, a weak C-F⋯π-electron ring inter-action was observed in the crystal packing [F⋯Cg = 3.459 (4) Å; Cg is the centroid of the pyrimidine ring]. There is also an intra-molecular N-H⋯Br inter-action in the structure.

Rational design based on bioactive conformation analysis of pyrimidinylbenzoates as acetohydroxyacid synthase inhibitors by integrating molecular docking, CoMFA, CoMSIA, and DFT calculations.

Pyrimidinylthiobenzoates constitute an important kind of herbicides targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6), which catalyze the first common step in branched-chain amino acid biosynthesis. Due to the symmetry of 4,6-dimethoxypyrimidyl, there are two kinds of conformation of pyrimidinylthiobenzoates: one's phenyl is left-extending (named conformation-L); the other's phenyl is right-extending (named conformation-R). On the basis of the assumption that 3D quantitative structure-activity relationship (QSAR) models derived from the bioactive conformation should give the best result, a strategy of density-functional-theory-based 3D-QSAR was proposed to identify the bioactive conformation of pyrimidinylthiobenzoates by integrating the techniques of molecular docking, comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and density functional theory calculation. The combination of three criteria of q2, r2, and r2pred obtained from CoMFA and CoMSIA analyses clearly indicated that conformation-R rather than conformation-L might be the bioactive conformation for pyrimidinylthiobenzoates. A further comparison between the two binding modes indicated that pyrimidinylthiobenzoates and sulfonylureas have very similar binding sites, such as Trp586, Arg380, and Pro192. However, Lys251 formed H bonds with sulfonylureas rather than pyrimidinylthiobenzoates. In addition, the orientation of phenyl groups of the two classes of compounds in the binding pocket were revealed to be opposite, which explained why the mutation of Pro192 displayed different sensitivity to sulfonylureas and pyrimidinylthiobenzoates. On the basis of the understanding of interactions between pyrimidinyl-thiobenzoates and AHAS, we designed and synthesized six 8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives according to the 3D-QSAR models. The excellent correlation between the tested Ki values against wild-type A. thaliana acetohydroxyacid synthase and the predicted IC50 values demonstrated the high reliability of the established 3D-QSAR models. To our knowledge, this is the first report highlighting the binding mode of herbicidal pyrimidinylthiobenzoates, which consisted of the reported results of herbicide resistance.

Design and syntheses of novel phthalazin-1(2H)-one derivatives as acetohydroxyacid synthase inhibitors.

A series of 2-substituted-8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives, 7a-7w, were designed via an ortho-substituent cyclization strategy to discover a new herbicidal lead structure. These compounds were synthesized by a seven-step route using 3-hydroxy-acetophenone as a starting material. Determination of the Ki values against wild-type A. thaliana acetohydroxyacid synthase (AHAS) (EC 4.1.3.18) indicated that some of the compounds displayed good enzyme inhibition activity comparable to that of KIH-6127. The further preliminary bioassay data on weeds showed that the synthesized compounds exhibited typical injury symptoms of AHAS-inhibiting herbicides, and some of them showed broad-spectrum and high herbicidal activities in postemergence treatments against Echinochloa crusgalli, Digitaria sanguinalis, Setaria viridis, Brassica juncea, Amaranthus retroflexus, and Chenopodium album at an application rate of 150 g ai/ha. To our knowledge, this is the first report of methylphthalazin-1-one derivatives as AHAS inhibitors.

[Studies on character variation of parent of "Ganzaoxian 47" by space mutation].

OBJECTIVE: To breed a new variety from "86-70 selective line"--a late-maturing early indica rice variety with small spike, light grain and weak disease resistance by space mutation. METHOD: Dry seeds of "86-70 selective line" were carried by recoverable satellite, to a near earth orbit and sowed and planted on the earth after recovery, heritance and variation of the characters of SP1- SP9 generation were observed. RESULT: Because of comprehensive space mutation, the characters of their progenies were segregated and varied in many aspects and directions, and the segregated and varied characters were found to be heritable; by selecting early-maturing mutants from these progenies and cultivating them directionally, a new rice variety "Ganzaoxian 47 " was bred. In comparison with its parent, "Ganzaoxian 47" had superior agronomic and economic characters, significantly strong resistance to rice blast and so on, its filled grains per spike [correction of spile], kilo-grain weight and yield were increased by 37.9%, 5.3% and 22.5% respectively, but its growth and developmental duration were shortened by 14 d. CONCLUSION: This study provided a new demonstration for space mutation breeding by recoverable satellite, and indicated that space mutation was an effective and new approach to agricultural crops breeding.

[Rice breeding by space technology].

In order to inquire into the influences of space conditions on rice breeding,the dry seeds of 12 rice varieties were carried by recoverable satellite. After recovery,these seeds were showed in the yield, the inheritance and variation of the characters of their progenies were observed and analysed. The results showed that the characters of the progenies mutated under space conditions segregated and varied in many aspects and directions,and the segregated and varied characters were heritable. These progenies posoessed significant transgressive inheritance, a plenty of variation types and variation was characterized by short breeding period. The results in this study indicated that space technology breeding could be developed and used as a new method of mutation breeding.

Treatment of extremity infections with soft tissue defects with the ramified musculocutaneous flap pedicled with the descending branch of lateral circumflex femoral artery / 中华显微外科杂志

Objective To discuss the clinical effect of the ramified musculocutaneous flap pedicled with the descending branch of lateral circumflex femoral artery treatment of bones and arthrsis of extremity in- fections with soft tissue defects.Methods The muscle flap blooded with the muscular branch of lateral fem- oral muscle and musculocutaneous flap blooded with the musculocutaneous branch were designed,all of which were pedicled with the descending branch of lateral circumflex femoral arteryIn clinic24 cases of bones and arthrosis of extremity infections with soft tissue defects were treated with this kind of ramified musculocutaneous flap.Results Of the 24 cases23 cases were survived while 1 case was lost16 cases were healed at stageⅠ8 cases were healed at stageⅡSinus has formated in 3 casesone of which twicebut they were healed in one year with the treatment of debridmentsFour cases with osteomvelitis and bone defect were treated with bone grafting in the later 6～8 months after the wound has healedTwenty-two cases were followed-up for 6～20 monthsinfcetiou didn't recur.Conclusion This kind of ramified musculocutaneous flap has such ad- vantages as longer blood vessel pediclefilling the defects completely flexible application and stronger anti-in- fectionthat it may be an effective way in treating bones and arthrosises of extremity infections with soft tissue defects.