Search

The main characteristics of panic disorder (PD) include recurrent panic attacks and persistent worry, accompanied by other physical and cognitive symptoms. While recent studies have revealed that gut bacteria play an important role in anxiety and depression, little is known about the relationship between oral microbiota and PD. Therefore, the objective of this study was to explore a possible correlation between oral microbiota and PD. We conducted 16S rRNA sequencing to compare differences in the oral microbiota of patients with PD (n = 26) and healthy controls (n = 40). Patients with PD exhibited higher alpha diversity (abundance and evenness) in their oral microbiota than healthy controls, while analysis of beta diversity revealed that the two groups differed in microbial community composition. Moreover, the relative abundance of 61 genera differed between them. Overall, PD resulted in distinct oral microbial profiles that could be potential diagnostic markers and therapeutic targets.

Posaconazole is the second-generation triazole antifungal agent with widespread clinical application. Posaconazole exposure is influenced by various factors such as drug interactions, disease state and diet, resulting in a high interindividual variability in many patients and failure to ensure therapeutic efficacy. Therefore, it is necessary to conduct individualized therapy on posaconazole to ensure the efficacy and safety of treatment.Articles were identified through PubMed using the keywords such as "posaconazole," "therapeutic drug monitoring" and "Population pharmacokinetics" from 1 January 2001 to 30 April 2022.In this paper, we review the individualized treatment studies of posaconazole from the three aspects of therapeutic drug monitoring, population pharmacokinetic study and Monte Carlo simulation to provide reference for in-depth individualized posaconazole dosing studies.This review suggests that therapeutic drug monitoring should be performed in patients taking posaconazole to adjust the dosage and assess the efficacy and cost-effectiveness of posaconazole under different clinical conditions and different dosing regimens through Monte Carlo simulations. In the future, a more detailed delineation and comprehensive examination of posaconazole PPK for specific populations requires further study.

Chemical-induced hematotoxicity is an important concern in the drug discovery, since it can often be fatal when it happens. It is quite useful for us to give special attention to chemicals which can cause hematotoxicity. In the present study, we focused on in silico prediction of chemical-induced hematotoxicity with machine learning (ML) and deep learning (DL) methods. We collected a large data set contained 632 hematotoxic chemicals and 1525 approved drugs without hematotoxicity. Computational models were built using several different machine learning and deep learning algorithms integrated on the Online Chemical Modeling Environment (OCHEM). Based on the three best individual models, a consensus model was developed. It yielded the prediction accuracy of 0.83 and balanced accuracy of 0.77 on external validation. The consensus model and the best individual model developed with random forest regression and classification algorithm (RFR) and QNPR descriptors were made available at https://ochem.eu/article/135149 , respectively. The relevance of 8 commonly used molecular properties and chemical-induced hematotoxicity was also investigated. Several molecular properties have an obvious differentiating effect on chemical-induced hematotoxicity. Besides, 12 structural alerts responsible for chemical hematotoxicity were identified using frequency analysis of substructures from Klekota–Roth fingerprint. These results should provide meaningful knowledge and useful tools for hematotoxicity evaluation in drug discovery and environmental risk assessment.

The resistance of Candida albicans (C. albicans) to classical antifungals has been increasing significantly and poses great challenges to clinical treatment. The objective of this research is to ev...

Botulinum neurotoxins (BoNTs) block the release of a series of neurotransmitters, which are pivotal for neuron action. Intrahippocampal administration of BoNTs inhibits glutamate release, protects neurons against cell death, and attenuates epileptic seizures. Compared with intrahippocampal administration, intranasal delivery is less invasive and more practical for chronic drug administration. To assess whether intranasal administration is feasible, we examined the role of botulinum neurotoxin A (BoNT/A) in hippocampal neuronal injury after status epilepticus (SE) induced by pilocarpine. Our data showed BoNT/A could bypass the blood-brain barrier (BBB) and entered the olfactory bulb and hippocampal neurons. In addition, SE could result in up-regulation of pro-apoptotic proteins (Caspase-3, Bax), down-regulation of anti-apoptotic protein Bcl-2 and neuronal death in hippocampus. BoNT/A could suppress the expression of Caspase-3 and Bax, attenuate the decrease of Bcl-2, and inhibit hippocampal neuron death induced by SE. Meanwhile, there was no significant difference in cognitive behavior between the BoNT/A-pretreated rats and normal rats. Thus, we provided a more convenient and less invasive route for taking advantage of BoNT/A in the field of anti-epilepsy.

To analyze the characteristics and relative factors of headache and neck pain due to cervicocerebral artery dissection (CAD). A total of 146 consecutive patients with CAD in Zhengzhou, China (2010–2017) were observed and registered prospectively. There were 60 (60/146) cases who complained of headache and neck pain, and we analyzed the characteristics of pain according to their clinical features. For the 130 (130/146) patients with complete clinical laboratory data, they were divided into two groups according to pain, and the relative factors of pain were analyzed. The headache and neck pain in 60 CAD patients was mostly acute onset (98.3%), 70.6% (12/17) of patients with anterior circulation dissection and 88.4% (38/43) of patients with posterior circulation dissection complained of moderate to severe pain. 41.2% (7/17) of patients with anterior circulation dissection had temporal pain, while 46.5% (20/43) of the patients with posterior circulation dissection had occipital pain. There were 23.5% (4/17) and 32.6% (14/43) of patients with anterior and posterior circulation dissection complained of throbbing pain, respectively, 23.5% (4/17) and 20.9% (9/43) of patients with anterior and posterior circulation dissection complained of pulsating pain. The pain could occur in the ipsilateral (40.0%), bilateral (52.7%), or contralateral (7.3%) sites of the dissection. In the 130 patients, there were 56 cases (43.1%) in the pain group, and 74 cases (56.9%) in the non-pain group. Multivariate logistic regression analysis showed that female gender (OR 4.01, 95% CI 1.63–9.85, P = 0.002), posterior circulation (OR 3.18, 95% CI 1.39–7.28, P = 0.006), history of headache (OR 4.72, 95% CI 1.08–20.52, P = 0.039), and low-density lipoprotein less than 1.8 mmol/L (OR 2.90, 95% CI 1.15–7.34, P = 0.025) were risk factors of the occurrence of the pain related to CAD. The headache and neck pain caused by CAD is a moderate to severe pain occurring suddenly. The pain nature may be diverse but mostly like throbbing and pulsating. When the dissected artery is located in the posterior circulation, the pain is mostly in the occipital region, and mostly in the temporal region when the dissected artery is located in the anterior circulation. The pain can occur in ipsilateral, bilateral, or contralateral of the dissection. In addition, several factors might contribute to the occurrence of headache and neck pain.

Cervicocerebral artery dissection (CAD) is a major cause of ischemic stroke in young adults. There are many existing studies on determinants for CAD; however, they are still not totally defined. We conduct the study to further investigate the determinants for CAD based on ischemic stroke patients. 81 ischemic stroke patients with CAD were enrolled in the CAD stroke group and 84 ischemic stroke patients without CAD were enrolled in the non-CAD stroke group. Their clinical data, such as age, gender, vascular risk factors, headache and neck pain and clinical laboratory data, were collected to analyze the differences between the two groups. A total of 165 ischemic stroke patients were included. The mean age of CAD stroke group was (51.6 ± 12.4) years, and (55.5 ± 8.1) years in non-CAD stroke group, with a statistically significant difference (P = 0.017). The average level of triglycerides in CAD stroke group was (1.3 ± 0.7) mmol/L, and (1.7 ± 1.1) mmol/L in non-CAD stroke group, with a statistically significant difference (P = 0.012). There were 42.0% (34/81) of headache and neck pain in CAD stroke group and 22.6% (19/84) in non-CAD stroke group, with a statistically significant difference (P = 0.008). The key findings with significant difference were stratified and multivariate logistic regression analysis showed that age

The resistance ofThe antifungal effect on resistant planktonicLND in combination with FLC exhibited synergistic antifungal effects against resistant planktonicLND combined with FLC exhibited synergistic antifungal activity against resistantThe emergence of fluconazole-resistant

Dynamically vulcanized thermoplastic olefin based on polypropylene (PP)/ethylene–propylene–diene (EPDM) with different dicumyl peroxide (DCP) content was prepared by twin-screw extruder. The effect...

Objective: To identify the predictors of ischemic events secondary to cervicocerebral artery dissection (CAD). Methods: Consecutive patients with cervicocerebral artery dissection from 2010 to 2017 were registered as study subjects, who were classified as patients with and without ischemic events. Clinical data were collected prospectively, such as demographics, vascular risk factors, headache and neck pain, dissection site and laboratory test. A case-control study was performed to compare the clinical data between two groups. Results: A total of 130 patients with cervicocerebral artery dissection were included, in which 70.0% (91/130) suffered from ischemic events, including 81 ischemic strokes and 10 transient ischemic attacks. There were 46.2% (42/91) and 25.6% (10/39) of the artery dissections located in the anterior circulation in the CAD patients with and without ischemic events respectively (p=0.029). The average level of HDL was (1.14±0.38) mmol/L in the CAD patients with ischemic events, and (1.28±0.48) mmol/L in the CAD patients without ischemic events (p=0.083). However, no significant differences were found in the other clinical data. Multivariate logistic regression analysis showed that there was a positive correlation between anterior circulation and ischemic events (OR=3.204, 95% CI 1.305-7.863, p=0.011) and HDL level was negatively correlated with ischemic events (OR=0.335, 95% CI 0.130-0.867, p=0.024) in CAD patients. Conclusion: Ischemic events are common complications of cerebrovascular disease in CAD patients, especially for those with an artery dissection located in the anterior circulation and low serum HDL level. Key Word: cervicocerebral artery dissection, ischemic event, HDL, anterior circulation, predictor

Readily available 1-sulfonyl-1,2,3-triazoles were converted into α-imino carbenes in the presence of catalytic amounts of rhodium(II) salts. The carbenes underwent a tandem reaction with salicylaldehydes to provide a series of functionalized 2,5-epoxybenzo[f][1,4]oxazepines in high yields.

合成了双水杨醛缩二乙烯三胺席夫碱（H 2 L）及其Cu 2+ 配合物（CuL·H 2 O），并对其进行了表征. 利用分光光度法考查了CuL·H 2 O催化降解甲基橙和酸性蓝9 的性能，利用HPLC法测定了降解产物. CuL·H 2 O 能催化甲基橙降解，但效果较差，催化降解产物为顺式丁烯二酸. 该配合物能催化酸性蓝9 降解，37℃条件下降解脱色率达到90%以上，其降解动力学符合酶促反应特征，具有明显的延滞期、线性期和缓慢期. 测得米氏常数 K m = 2.006 × 10 -5 mol/L，降解产物为顺式丁烯二酸. 推测了CuL·H 2 O 作为仿酶催化剂的催化机理和酸性蓝9的降解机制. 说明CuL·H 2 O 具有优良的仿酶特性和底物选择性.

Sodium iodide is used for the first time as a nucleophile to trap an α-imino rhodium carbene, which triggers a tandem process involving intermolecular nucleophilic attack and intramolecular SN2 reaction. A series of 5-iodo-1,2,3,4-tetrahydropyridines are obtained in high yield, and the synthetic utility of the products is demonstrated in cross-coupling reactions and the construction of biorelated polycyclic compounds.

Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the α-imino rhodium carbene formed in the presence of the rhodium catalyst.

Readily available 1-sulfonyl-1,2,3-triazoles were converted into α-imino carbenes in the presence of catalytic amounts of rhodium(II) salts. The carbenes underwent a tandem reaction with salicylaldehydes to provide a series of functionalized 2,5-epoxybenzo[f][1,4]oxazepines in high yields.

Highly functionalized 4-bromo-1,2-dihydroisoquinolines were synthesized from readily available 4-(2-(bromomethyl)phenyl)-1-sulfonyl-1,2,3-triazoles. A bromonium ylide is proposed as the key intermediate, which can be formed by the intramolecular nucleophilic attack of the benzyl bromide on the α-imino rhodium carbene formed in the presence of the rhodium catalyst.

In the presence of a Rh(II) catalyst and β-(methylthio)-α,β-unsaturated ketones, 1-sulfonyl-1,2,3-triazoles can be converted into functionalized β-amino-α,β-unsaturated ketones via formation of α-imino rhodium carbene/sulfur ylide and subsequent rearrangement. The products decompose to useful 2-methylthiopyrrole derivatives conveniently in high yield.

In the presence of a Rh(II) catalyst and β-(methylthio)-α,β-unsaturated ketones, 1-sulfonyl-1,2,3-triazoles can be converted into functionalized β-amino-α,β-unsaturated ketones via formation of α-imino rhodium carbene/sulfur ylide and subsequent rearrangement. The products decompose to useful 2-methylthiopyrrole derivatives conveniently in high yield.

R&D outsourcing is another management form which can relieve enterprises from complexly daily activities and strengthen enterprises' competitiveness with the exception of human resources outsourcing and financial outsourcing. However, there are great risks involved in R&D outsourcing. The paper aimed at determining key risks of R&D outsourcing and making countermeasures for avoiding them. The paper, based on the concept and connotation of R&D outsourcing, analyzed risks during outsourcing at a strategic level and concluded that risks of R&D outsourcing should focus on risk of business strategic analysis, risk of decision-making on R&D outsourcing, risk of selection and management of service provider and risk of performance evaluation on R&D outsourcing. Finally the paper proposed preventive measure against the risks.

To perform apple polyploid breeding the ways of inducing polyploidy pollen with temperature and chemicals were studied. Materials include 13 diploid cultivars: Red Chief, Dai Hong, Rose Red, Golden Delicious, Mollie's Delicious, Gala, Bella, Jonathan, Fuji, Qiu Kou Hong, and Yan Qing, OBIR-2T-47. Chemicals: Chloroform, N-nitroso-ethylurea. At the beginning of PMC meiosis, fruiting branching groups were covered with plastic bags to raise temperature or were treated with chemical. After covering, temperature during the day increased 2 °C, generally not lower than 0 °C. Whether branches received high temperature or chemicals treatment, polyploidy pollen was induced to produce. The pollen grain of CK is tricolporat, its polar view is triangular, and its diameter almost 40 μm, showing no difference in size. Rate of empty pollen grain is low. Pollen grains that were treated were different in size, and rate of empty pollen is high, part of pollen grains germinating colporat change into tetracolporat with a few polycolporat, its polar view is square, round, and oval. The diameter of large pollen grains was 45-48 μm, increased by 11-12%. Giant pollen grain are 50-68 μm, increased by 25%-70%. Rate of induction is different in different cultivars. For most cultivars, giant pollen grain is 0.3%-0.5%. Gala and OBIR-2T-47 were higher, reaching 2.5%-7%. Chemicals caused damage on cultivars. Delicious strains were easily damaged.

Laiyang dwarf cherry (Prunus pseudocerasus Lindl. Var. Laiyang dwary cherry) is an important dwarf type of Chinese cherry. It is both directly used for production and used as rootstock of sweet cherry (P. avium L.). Material used in this study was Laiyang dwarf cherry seed, which is open-pollinated. The fruit surface is sterilized with 70% ethanol on sterile working table, the seed is removed from fruit, and embryo is taken out of cracking seed shell. Explants include whole embryo, embryo without cotyledons, and cotyledons. Basal media are MS and 1/4MS major elements, sugar 30 g·L–1, agar 5.5 g·L–1, adjusted pH 5.8. Hormone used included 6-BA,IBA and 2,4-D for a total eight treatments. Culture temperature was 25° ±2°C, and photoperiod was 14 h. Results show 1) the plant regeneration rate from cotyledons is highest, second is from embryo without cotyledons, lowest is from whole embryo; 2) when BA is in the range of 0.7 to 5 ppm, plant regeneration is higher at a high concentration than that at low concentration; 3) at the same concentration, plant regeneration rate on the medium supplemented with 2,4-D is higher than that on the medium supplemented with IBA; 4) plant regeneration rate is higher on the medium containing cytokinin and auxin is higher than that on the medium only containing cytokinin; and 5) plant regeneration rate of continuous light culture cotyledons is higher than that of first dark culture 2 weeks cotyledons. Effects of light and dark/hormone and explant type on plant regeneration rate is discussed.

Plant mutation induced with colchicine, disturbance of chimeras has long been unsolved. Authors used embryo culture in vitro induced with colchicine for inducing genome of embryonic cells of diploid apple to be doubled, cell doubled differentiated into adventitious shoots, and then were culture into plantlets. By morphological preselection, plants induced hundreds of genotypes had been obtained. To identify ploidy variation of three histogenic layers of shoot apices, sections of shoot apices of 284 plants were identified. Two-hundred-forty-nine tetraploid plants were selected. Entire mutants accounted for 98%, chimeras 2%. This proved that induction in vitro could indeed eliminate disturbance of chimeras and was a new induction technique simply and effectively. Accurate rate of morphological preselection was confirmed by 87.7% by sections of shoot apices. The identification of ploidy of mutated plants of apple in vitro induced with colchicine, the method of combining morphological preselection with sections of shoot apices had advantages over that of chromosome count. First, the method is simple, saving time and labor, with a high success rate and reliable results. Second, whether the mutated plants were chimeras and chimera structures could be known. Main criteria of identifying ploidy by sections of shoot apices are the size of cells, nuclei, and nucleoli and numbers of nucleoli of three histogenic layers of shoot apices. Morphological characters of tetraploid were dumpy, thick, and strong stem with short internodes; small petiole angle; broad-round thick leaves with dark green color; round leaf base; thick and sharp-pointed sawteeth; protruding and clear main vein.

Feicheng peach is a famous cultivar of Prunus persica. Not only the fruits which are giant with superfine flavour are out of ordinary, but also the meiotic behaviour of PMC is abnormal. About 40–100% of the anthers were found to have a few binucleate microsporocytes in company with normal single ones. The binucleate microsporocyte is about 2 times as large as single microsporocyte. It is neither an end product of cytomixis nor a giant microsporocyte and is characterized by having two nuclei in a common elliptical cell wall. The two protoplasts divide independently and consequently to give octads instead of tetrads. Poly—nuclei and poly—nucleoli were observed in some microsporocytes at prophase I. At telophase I. II. nearly all the microsporocytes contained poly—nuclei and poly—nucleoli. This is also true in some of the microspores. Both the number and the size of poly-nuclei in each microsporocyte and of poly—nucleoli in each nucleus were diverse. At telophase II, about 74% of single microsporocytes produced tetrads, and the rest formed diads. triads, unequal tetrads, pentads, hexads, heptads or octads. The microspores formed were unequal in size except those formed from diads. Most binucleate microsporocytes produced octads. and a few formed hexads, heptads. enneads or decads. Their microspores are nearly equal in size.

In the 1980' s, a Bartlett pear giant fruit sport was found in Pingdu, Shandong. The characteristics of mutation are larger fruit, thicker branch, shorter internode and much more spur. By grafting propagation, the clones began to bear fruit in 1990, and maintain the characteristics of variable mother plant. From microspore formation to blossom and spreading pollen, the cytohistological observation of sport flowering organs indicates: in every phase of pollen development, the size of florets, anthers and pollen grains are similar to CK; their pollen types both belong to tricolporat, pollen grains are nearly equal in size. This indicates that sport sporogenous tissue do not mutate. The observation of shoot apex sections showes: for CK, the cells of three histogenic layers range regularly; the size of cells, nuclei, and nucleoli among LI, LII, LIII are similar. For sport, the cells of LI, LII are no difference from CK, but in LIII and inner tissue, cells, nuclei, nucleoli all become larger clearly. This indicates LIII had mutated. So this sport is a 2–2–4 type chimera.