Clinical observation of a modified technique for intrascleral fixation of flanged three-piece foldable intraocular lenses through a Hoffman pocket.

Purpose: To present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision. Materials and methods: We retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique. Results: The follow-up period ranged 3-12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure. Conclusion: Our novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients' recovery.

WW domains form a folded type of nuclear localization signal to guide YAP1 nuclear import.

The nuclear translocation of YAP1 is significantly implicated in the proliferation, stemness, and metastasis of cancer cells. Although the molecular basis underlying YAP1 subcellular distribution has been extensively explored, it remains to be elucidated how the nuclear localization signal guides YAP1 to pass through the nuclear pore complex. Here, we define a globular type of nuclear localization signal composed of folded WW domains, named as WW-NLS. It directs YAP1 nuclear import through the heterodimeric nuclear transport receptors KPNA-KPNB1, bypassing the canonical nuclear localization signal that has been well documented in KPNA/KPNB1-mediated nuclear import. Strikingly, competitive interference with the function of the WW-NLS significantly attenuates YAP1 nuclear translocation and damages stemness gene activation and sphere formation in malignant breast cancer cells. Our findings elucidate a novel globular type of nuclear localization signal to facilitate nuclear entry of WW-containing proteins including YAP1.

Regulation of Rhesus glycoprotein-related genes in large-scale loach Paramisgurnus dabryanus during ammonia loading.

Waterborne ammonia is one of the crucial issues that limited production and animal health in aquaculture. Ammonia-tolerant varieties are highly desired in intensive fish farming. Screening for the key regulatory genes of ammonia tolerance is essential for variety breeding. According to the previous hypothesis, Rh glycoproteins play an important role in ammonia excretion in teleosts. However, the ammonia defensive mechanisms are not well described at present for large-scale loach (Paramisgurnus dabryanus), a typical air-breathing and commercially important fish in East Asia. Here we show that the transcription of Rh glycoprotein-related genes was significantly affected by ammonia exposure in this species. Probit analysis showed that 96 h-LC50 of NH4Cl at 23 â„ƒ and pH 7.2 was 92.64 mmol/L. A significant increase of Rhcg expression in gills was observed after 48 h of 60 mmol/L and 36 h of 80 mmol/L NH4Cl exposure, suggesting that Rhcg present on the apical side of the branchial epithelium facilitates NH3 excretion out of gills. A high concentration of acute ammonia exposure induced elevated Rhbg transcript in the gills of large-scale loaches, while a slight change in Rhbg expression was observed in response to lower ammonia, suggesting that transcriptions of Rhbg genes are activated by a considerably high level of ambient ammonia to eliminate excessive endogenous nitrogen. The Rhag mRNA level in gills of large-scale loaches increased markedly with the prolonging of exposure time from 0 to 36 h of ammonia loading, suggesting Rhag localized in gills may be primarily associated with ammonia handling. During 7-21 days of ammonia exposure, the expression of most Rh glycoproteins-related genes in the gills decreased, indicating that the functional role of Rh glycoproteins is not primarily associated with ammonia defense over a long period (more than 7 days). Although a significant transcript of Rhbg was found in the skin of a large-scale loach, the lack of Rhcg and down-regulation of Rhag may indicate that the skin is not an essential location of ammonia excretion, at least when submerged to high levels of ammonia in the environment. In conclusion, Rh glycoproteins localized in gills as ammonia transporters play a momentous role in ammonia detoxification in this species during acute ammonia loading. However, it does not show a positive function during long-term ammonia exposure. Furthermore, the physiological function of Rh glycoproteins localized in the skin is still unclear and deserves further study.

FNDC5/irisin facilitates muscle-adipose-bone connectivity through ubiquitination-dependent activation of runt-related transcriptional factors RUNX1/2.

In the past decade, the cleavage protein irisin derived from fibronectin type III domain-containing protein 5 (FNDC5) in exercise-stimulated skeletal muscle has increasingly become a biomarker associated with metabolic syndrome and osteoporosis in humans. However, it is unclear how this protein facilitates muscle-adipose-bone connectivity in metabolic and skeletal homeostasis. In this study, we unexpectedly observed that the FNDC5 gene can be markedly activated during the differentiation of brown adipocytes but not white adipocytes, and that FNDC5 is specifically expressed in mouse brown adipose tissues (BATs). But unlike it in the skeletal muscles, the expression of FNDC5/irisin in BAT is promoted by cold exposure rather than exercise in mice. Analysis of promoter activity and chromatin immunoprecipitation further showed that peroxisome proliferator-activated receptor γ coactivator-1α and thyroid hormone receptors cooperate on the FNDC5 gene promoter to induce its transcription. We found that FNDC5/irisin stimulates the runt-related transcriptional factors RUNX1/2 via a focal adhesion kinase-dependent pathway in both bone and subcutaneous white adipose tissues. Mechanistically, focal adhesion kinase is stimulated by FNDC5/irisin and then facilitates E3 ubiquitin-protein ligase WW domain-containing protein 2 to ubiquitinate and subsequently activate RUNX1/2, culminating in the activation of osteoblast-related or thermogenesis-related genes. Interestingly, the PR domain containing protein 16 that is crucial for subcutaneous white adipose "browning" and skeletal development was found to form a complex with RUNX1/2 in a WW domain-containing protein 2-dependent manner. These findings elucidate a signaling mechanism by which FNDC5/irisin supports the muscle-adipose-bone connectivity, especially BAT-bone connectivity.

Transcriptomic analyses of the acute aerial and ammonia stress response in the gill and liver of large-scale loach (Paramisgurnus dabryanus).

The large-scale loach (Paramisgurnus dabryanus) is one of the most commercially important cultured species. Ammonia nitrogen accumulation is one of the key issue which limited production and animal health in aquaculture, but few of information is available on the molecular mechanisms of ammonia detoxification. We performed transcriptomic analyses of the gill and liver of large-scale loach subjected to 48 h of aerial and ammonia exposure. We obtained 47,473,424 to 56,791,496 clean reads from the aerial exposure, ammonia exposure and control groups, assembled and clustered a total of 92,658 unigenes with an average length of 909 bp and N50 of 1787 bp. Totals of 489/145 and 424/140 differentially expressed genes (DEGs) were detected in gill/liver of large-scale loach after aerial and ammonia exposure through comparative transcriptome analyses, respectively. In addition, totals of 43 gene ontology (GO) terms and 266 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified. After aerial and ammonia exposure, amino acid metabolism pathways in liver of large-scale loach were significantly enriched, suggesting that large-scale loach responded to high exogenous and endogenous ammonia stress by enhancing amino acid metabolism. Besides, the expression of several ammonia transporters (i.e., Rhesus glycoproteins and Aquaporins) in gill of large-scale loach were markedly changed after 48 h of aerial exposure, suggesting that large-scale loach responded to high endogenous ammonia stress by regulating the expression of Rh glycoproteins and Aqps related genes in gill. The results provide valuable information on the molecular mechanism of ammonia detoxification of large-scale loach to endogenous and environmental ammonia loading, will facilitate the molecular assisted breeding of ammonia resistant varieties, and will offer beneficial efforts for establishing an environmental-friendly and sustainable aquaculture industry.

A Middle Eocene lowland humid subtropical "Shangri-La" ecosystem in central Tibet.

Tibet's ancient topography and its role in climatic and biotic evolution remain speculative due to a paucity of quantitative surface-height measurements through time and space, and sparse fossil records. However, newly discovered fossils from a present elevation of ∼4,850 m in central Tibet improve substantially our knowledge of the ancient Tibetan environment. The 70 plant fossil taxa so far recovered include the first occurrences of several modern Asian lineages and represent a Middle Eocene (∼47 Mya) humid subtropical ecosystem. The fossils not only record the diverse composition of the ancient Tibetan biota, but also allow us to constrain the Middle Eocene land surface height in central Tibet to ∼1,500 ± 900 m, and quantify the prevailing thermal and hydrological regime. This "Shangri-La"-like ecosystem experienced monsoon seasonality with a mean annual temperature of ∼19 °C, and frosts were rare. It contained few Gondwanan taxa, yet was compositionally similar to contemporaneous floras in both North America and Europe. Our discovery quantifies a key part of Tibetan Paleogene topography and climate, and highlights the importance of Tibet in regard to the origin of modern Asian plant species and the evolution of global biodiversity.

Overexpression a "fruit-weight 2.2-like" gene OsFWL5 improves rice resistance.

BACKGROUND: Rice (Oryza sativa) feeds half of the world's population. Rice grain yield and quality which are constrained by diseases and mineral nutritions have important human healthy impacts. Plant "fruit-weight 2.2-like" (FWL) genes play key roles in modulating plant fruit weight, organ size and iron distribution. Previous work has uncovered that the grains of OsFWL5-oeverexpressing rice accumulated more beneficial element zinc (Zn) and less toxic element cadmium (Cd) content. However, whether FWL genes play roles in rice resistance remains unknown. FINDINGS: Here, we validated that one of rice FWL genes OsFWL5 plays a positive role in defense to Xanthomonas oryzae pv. oryzae (Xoo). Overexpresion of OsFWL5 promotes H2O2 accumulation and cell death. The OsFWL5-overexpresing plants show activated flg22-induced reactive oxygen species (ROS) generation, and increased resistance to Xoo, indicating that OsFWL5 functions to increase pathogen-associated molecular pattern (PAMP)-triggered immunity in rice. The activated defense response is associated with increased the expression of genes involved in jasmonic acid (JA)-related signaling. Furthermore, Cd can induce rice resistance to Xoo, and OsFWL5 is required for Cd-induced rice defense response. CONCLUSION: Putting our finds and previous work together, OsFWL5 could be a candiate gene for breeders to genetically improve rice resistance and grain quality.

Jasmonic Acid-Involved OsEDS1 Signaling in Rice-Bacteria Interactions.

BACKGROUND: The function of Arabidopsis enhanced disease susceptibility 1 (AtEDS1) and its sequence homologs in other dicots have been extensively studied. However, it is unknown whether rice EDS1 homolog (OsEDS1) plays a role in regulating the rice-pathogen interaction. RESULTS: In this study, a OsEDS1-knouckout mutant (oseds1) was characterized and shown to have increased susceptibility to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc), suggesting the positive role of OsEDS1 in regulating rice disease resistance. However, the following evidence suggests that OsEDS1 shares some differences with AtEDS1 in its way to regulate the host-pathogen interactions. Firstly, OsEDS1 modulates the rice-bacteria interactions involving in jasmonic acid (JA) signaling pathway, while AtEDS1 regulates Arabidopsis disease resistance against biotrophic pathogens depending on salicylic acid (SA) signaling pathway. Secondly, introducing AtEDS1 could reduce oseds1 mutant susceptibility to Xoo rather than to Xoc. Thirdly, exogenous application of JA and SA cannot complement the susceptible phenotype of the oseds1 mutant, while exogenous application of SA is capable of complementing the susceptible phenotype of the ateds1 mutant. Finally, OsEDS1 is not required for R gene mediated resistance, while AtEDS1 is required for disease resistance mediated by TIR-NB-LRR class of R proteins. CONCLUSION: OsEDS1 is a positive regulator in rice-pathogen interactions, and shares both similarities and differences with AtEDS1 in its way to regulate plant-pathogen interactions.

Hd3a and OsFD1 negatively regulate rice resistance to Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.

In rice, Hd3a, GF14 and OsFD1 proteins, forming florigen activation complex, are key components in flowering time regulation. GF14 genes in rice response to biotic and abiotic stress has also been well addressed. The role of GF14e in rice defense has been well studied. However, whether Hd3a and OsFD1 play roles in defense is unclear. In present study, we identified that Hd3a and OsFD1 expression is repressed by Xoo and JA, and validated that Hd3a and OsFD1 negatively regulate resistance to Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas oryzae pv. oryzicola (Xoc). hd3a and osfd1 mutants increase resistance to Xoo and Xoc, and activate JA responsive genes expression. Our data also demonstrate that OsFD1 binds to the promoters of and activates the expression of JAZ genes; Hd3a, cooperating with GF14e, promotes OsFD1 action on JAZ gene expression. The functional confirmation of Hd3a and OsFD1 in rice defense makes them to be promising targets in molecular rice breeding.