Identification of ferroptotic genes and phenotypes in idiopathic nonobstructive azoospermia.

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

Kinetically and thermodynamically controlled one-pot growth of gold nanoshells with NIR-II absorption for multimodal imaging-guided photothermal therapy.

Since the successful clinical trial of AuroShell for photothermal therapy, there is currently intense interest in developing gold-based core-shell structures with near-infrared (NIR) absorption ranging from NIR-I (650-900 nm) to NIR-II (900-1700 nm). Here, we propose a seed-mediated successive growth approach to produce gold nanoshells on the surface of the nanoscale metal-organic framework (NMOF) of UiO-66-NH2 (UiO = the University of Oslo) in one pot. The key to this strategy is to modulate the proportion of the formaldehyde (reductant) and its regulator / oxidative product of formic acid to harness the particle nucleation and growth rate within the same system. The gold nanoshells propagate through a well-oriented and controllable diffusion growth pattern (points → facets → octahedron), which has not been identified. Most strikingly, the gold nanoshells prepared hereby exhibit an exceedingly broad and strong absorption in NIR-II with a peak beyond 1300 nm and outstanding photothermal conversion efficiency of 74.0%. Owing to such superior performance, these gold nanoshells show promising outcomes in photoacoustic (PA), computed tomography (CT), and photothermal imaging-guided photothermal therapy (PTT) for breast cancer, as demonstrated both in vitro and in vivo.

Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex.

Alkaloids having acetylcholinesterase (AChE) inhibitory activity are commonly found in traditional Chinese medicine (TCM); for example, berberine from Coptis chinensis, galantamine from Lycoris radiata, and huperzine A from Huperzia serrata. In practice of TCM, Stephaniae Tetrandrae Radix (STR) is often combined with Coptidis Rhizoma (CR) or Phellodendri Chinensis Cortex (PCC) as paired herbs during clinical application. Fangchinoline from STR and coptisine and/or berberine from CR and/or PCC are active alkaloids in inhibiting AChE. The traditional usage of paired herbs suggests the synergistic effect of fangchinoline-coptisine or fangchinoline-berberine pairing in AChE inhibition. HPLC was applied to identify the main components in herbal extracts of STR, CR, and PCC, and the AChE inhibition of their main components was determined by Ellman assay. The synergism of herb combination and active component combination was calculated by median-effect principle. Molecular docking was applied to investigate the underlying binding mechanisms of the active components with the AChE protein. It was found that fangchinoline showed AChE inhibitory potency; furthermore, fangchinoline-coptisine/berberine pairs (at ratios of 1:5, 1:2, 1:1, and 2:1) synergistically inhibited AChE; the combination index (CI) at different ratios was less than one when Fa = 0.5, suggesting synergistic inhibition of AChE. Furthermore, the molecular docking simulation supported this enzymatic inhibition. Therefore, fangchinoline-coptisine/berberine pairs, or their parental herbal mixtures, may potentially be developed as a possible therapeutic strategy for Alzheimer's patients.

Polysaccharide deriving from Ophiopogonis Radix promotes metabolism of ginsenosides in the present of human gut microbiota based on UPLC-MS/MS assay.

The combined usage of Ginseng Radix et Rhizoma (ginseng) and Ophiopogonis Radix is common in oriental countries for thousands of years. The major active constituents of ginseng are ginsenosides, and the conversion of ginsenosides to different metabolites by gut microbiota has been reported. However, the effect of Ophiopogonis Radix, especially its polysaccharides, on the metabolism of ginsenosides by gut microbiota is not known. Here, an in vitro metabolism of ginseng extract, or ginsenosides, in combination with or without Ophiopogon polysaccharide was conducted. A sensitive and reliable UPLC-MS/MS approach using multiple reaction monitoring (MRM) in positive ion mode was developed simultaneously to quantify 22 ginsenosides in the broth of gut microbiota. After fermentation with the microbiota, 15 ginsenosides were detected and quantified, including 6 primary ginsenosides, i.e. Rb1, Rc, Rb2, Rb3, Rd and Re, and 9 metabolites, i.e. F2, Rg3, compound K, Rh2, PPD, Rg1, Rh1, Rg2 and PPT. The quantitative results therefore revealed the elimination of primary ginsenosides and the formation of their metabolites in time-dependent manners. Furthermore, Ophiopogon polysaccharide was shown to stimulate the metabolism of ginsenosides, triggered by gut microbiota. Our study can be extended to investigate the metabolism of different Panax species by gut microbiota when combining with other herbs.

[Dynamic evolution of landscape spatial pattern in Taihu Lake basin, China]. / å¤ªæ¹–æµåŸŸæ™¯è§‚ç©ºé—´æ ¼å±€åŠ¨æ€æ¼”å˜.

Based on the land-use satellite image datasets of 2000, 2010 and 2015, the landscape index, dynamic change model, landscape transfer matrix and CLUE-S model were integrated to analyze the dynamic evolution of the landscape spatial pattern of Taihu Lake basin. The results showed that the landscape type of the basin was dominated by cultivated land and construction land, and the degree of landscape fragmentation was strengthened from 2000 to 2015, and the distribution showed a uniform trend. From the point of transfer dynamic change, the cultivated land and construction land changed significantly, which was reduced by 6761 km2 (2.1%) and increased by 6615.33 km2 (8.4%), respectively. From the landscape transfer, it could be seen that the main change direction of the cultivated land reduction was the construction land, and the cultivated land with 7866.30 km2 was converted into construction land, accounting for 91.6% of the cultivated land change, and the contribution to the construction land was 96.5%. The trend of dynamic changes of cultivated and construction land in the counties and cities was the same as that of the whole Taihu Lake basin. For Shanghai Central Urban, as well as Pudong District, Lin'an City, Baoshan District, Minhang District, Jiading District and Changzhou City, the area of the cultivated land and construction land changed more prominently. However, compared with the CLUE-S model for the landscape pattern change in 2030, the change of cultivated and construction lands would be the largest in the natural development scenario. Under the ecological protection scenario, the area of grassland would increase and the dynamic degree would reach 54.5%. Under the situation of cultivated land protection, the conversion of cultivated land to construction land would be decreased.

[Ecological risk assessment of Taihu Lake basin based on landscape pattern]. / åŸºäºŽæ™¯è§‚æ ¼å±€çš„å¤ªæ¹–æµåŸŸç”Ÿæ€é£Žé™©è¯„ä¼°.

Taihu Lake basin was selected as the study site. Based on the landscape data of 2000, 2005, 2010 and 2015, the Markov and CLUE-S models were used to simulate the landscape types with different scenarios in 2030, and landscape ecological risk index was constructed. The shift of gravity center and spatial statistics were used to reveal landscape ecological risk of Taihu Lake basin with temporal and spatial characteristics. The results showed that the ecological risk mainly was at medium and low levels in Taihu Lake basin, and the higher ecological risk areas were mainly distributed at the Taihu Lake area during 2000 to 2015, and the low ecological risk was transferred from the southwest and south of Taihu Lake to the developed areas in the northern part of Taihu Lake area. Spatial analysis showed that landscape ecological risk had negative correlation with natural factors, which was weakened gradually, while the correlation with socioeconomic factors trended to become stronger, with human disturbance affecting the landscape ecological risk significantly. The impact of socioeconomic factors on landscape ecological risks differed in different urbanization stages. In the developing area, with the economic development, the landscape was increasingly fragmented and the ecological risk was correspondingly increased. While in the developed area, with the further development of the economy, the aggregation index was increased, and fragmentation and separation indexes were decreased, ecological construction was restored, and the landscape ecological risk began to decline. CLUE-S model simulation showed that the ecological risk of Taihu Lake basin would be reduced in future, mainly on the low and relatively low levels. Taihu Lake area, both in history and the future, is a high ecological risk zone, and its management and protection should be strengthened.

[Dynamic evolution of wetland landscape spatial pattern in Nansi Lake, China]. / å—å››æ¹–æ¹¿åœ°æ™¯è§‚ç©ºé—´æ ¼å±€åŠ¨æ€æ¼”å˜.

Based on Landsat images in 1987, 2002 and 2014 from Nansi Lake located in Shandong Province, landscape pattern index, dynamic index, landscape gradient and gridding model were used for analysis of the wetland distribution in the lake. The results showed that the landscape contagion index and aggregation index gradually decreased from 1987 to 2014, while the landscape diversity index and evenness index gradually increased. The distribution of landscape area was more uniform while its patterns trended to be fragmented. Human activities impacted Nansi wetland distribution and the disturbance presented an increasing trend. The total area of Nansi wetland gradually increased during the study period. The area of lake first decreased then increased, and the area reached the maximum in 2014. The area of the ponds along the riparian zone had increased gradually, but the increasing speed slowed down. The area of the rivers remained stable, while the area of the swamps decreased continually during the period. The change of landscape pattern of Nansi Lake wetland mainly resulted from agricultural activities, establishment of Nansi Lake Natural Reserve, and the South-to-North Water Diversion Project.

[Diagnosis and surgical management of 209 cases of orbital cavernous hemangioma].

OBJECTIVE: To study the clinical features, preoperative diagnosis and surgical choice of orbital cavernous hemangioma. METHODS: Records of all cavernous hemangioma patients (209 cases) who were seen in Eye Hospital, Zhongshan Ophthalmic Center, Sun Yat-sen University from January 1, 1986 to December 31, 2000 were reviewed. RESULTS: Among 209 cases, 123 patients were females and 86 were males. The left orbit was affected in 123 cases and the right orbit in 86 cases. No case was bilaterally involved. The mean age was 39.2 years old, ranging from 5 to 68 years. A painless, gradually progressive proptosis and visual disturbance were the main clinical signs. Ninety-five percent (199/209) of them could be accurately diagnosed preoperatively based on ultrasound scan and CT/MRI examination. The tumors were removed successfully by the surgical procedure of standard lateral orbitotomy in 36% (75/209) of patients and anterior orbitotomy in 64% cases (134/209). CONCLUSIONS: Nearly all patients with cavernous hemangioma could be correctly diagnosed by preoperative image studying. The simple surgical procedure of anterior orbitotomy can be successfully used in about two third of cases with less surgical complication.

[Clinical analysis of 339 cases of thyroid-associated ophthalmopathy].

OBJECTIVE: To summarize the clinical manifestation of thyroid-associated ophthalmopathy (TAO), to analyze the thyroid function and to monitor the therapeutic effect of anti-hyperthyroidism on the progression of TAO. METHODS: Three hundred and thirty nine TAO cases (597 eyes) were collected from 1994 to 2001 and their clinical manifestations were summarize and analyzed. RESULTS: TAO occurred mostly in individuals over 40 years with no gender preference. Exophthalmos and diplopia were the major manifestations and main reasons for ophthalmic examination. Retraction of eyelids and involvement of extraocular muscle were present in over 70% cases. In 339 TAO cases, euthyroidism was found in 93 cases and abnormal thyroid function (hyperthyroidism or hypothyroidism) was present in 246 cases. The V and VI grade of TAO occurred more frequently in patients with abnormal thyroid function than those with euthyroidism. (131)I, oral anti-hyperthyroidism drug, or thyroidectomy was used for all patients with abnormal thyroid function. TAO occurred in 39.3% cases treated with (131)I, in 15.6% cases with oral anti-hyperthyroidism drug, and in 14% cases with thyroidectomy. All ocular pathologic changes occurred after hyperthyroidism had been controlled and hypothyroidism was found in most of these cases. CONCLUSIONS: The condition of thyroid function has a certain relationship to the severity of TAO. Over-fast and undue anti-hyperthyroidism therapy may impact an untoward effect on TAO; immediate and appropriate treatment can improve the effect of therapy on TAO.