Efficacy of two different dosages of prednisone for treatment of subacute thyroiditis: a single-centre, prospective, randomized, open-label, non-inferiority trial.

INTRODUCTION: The study aimed to explore the efficacy and safety of low-dose (LD) and regular-dose (RD) prednisone (PDN) for the treatment of subacute thyroiditis (SAT). MATERIAL AND METHODS: Patients were randomly allocated using the block randomization method to the 2 groups. The primary outcome was the time required for PDN treatment. Secondary outcomes included percentages of relapse, mean score for the Morisky Medication Adherence Scale-8© (MMAS-8), time required for symptoms to resolve, cumulative PDN dose (mg), and mean erythrocyte sedimentation rate (ESR) at 2 weeks and at baseline. RESULTS: The study cohort included 77 patients, randomized 74 participants, and 68 completed the study. There was no significant difference in the treatment duration between the LD and RD groups (55.31 ± 14.05 vs. 61.25 ± 19.95 days, p = 0.053). The mean difference in the time required for PDN treatment between the LD and RD groups was -1.86 [95% confidence interval (CI) = -10.64 to 6.92] days, which was within the non-inferiority margin of 7 days. There was a significant difference in the mean score for MMAS-8 between the LD and RD groups (5.84 ± 0.88 vs. 5.33 ± 1.12, p = 0.031). Also, there was a significant difference in the cumulative PDN dose between the LD and RD groups (504.22 ± 236.86 vs. 1002.28 ± 309.86, p = 0.046). The ESR at 2 weeks was statistically significant compared to baseline values in both groups, with pre-treatment and post-treatment ESRs of 49.91 ± 24.95 and 17.91 ± 12.60/mm/h, (p < 0.0001) in the LD group and 65.08 ± 21.77 and 17.23 ± 13.61/mm/h (p < 0.0001) in the RD group. CONCLUSION: Low-dose PDN therapy may be sufficient to achieve complete recovery and better outcomes for SAT. This study is registered with the Chinese Clinical Trial Registry (02/10/2021 ChiCTR2100051762).

Mild thermotherapy and hyperbaric oxygen enhance sensitivity of TMZ/PSi nanoparticles via decreasing the stemness in glioma.

BACKGROUND: Glioma is a common brain tumor with a high mortality rate. A small population of cells expressing stem-like cell markers in glioma contributes to drug resistance and tumor recurrence. METHODS: Porous silicon nanoparticles (PSi NPs) as photothermal therapy (PTT) agents loaded with TMZ (TMZ/PSi NPs), was combined with hyperbaric oxygen (HBO) therapy in vitro and in vivo. To further investigate underlying mechanism, we detected the expression of stem-like cell markers and hypoxia related molecules in vitro and in vivo after treatment of TMZ/PSi NPs in combination with PTT and HBO. RESULTS: NCH-421K and C6 cells were more sensitive to the combination treatment. Moreover, the expression of stem-like cell markers and hypoxia related molecules were decreased after combination treatment. The in vivo results were in line with in vitro. The combination treatment presents significant antitumor effects in mice bearing C6 tumor compared with the treatment of TMZ, PTT or TMZ/PSi NPs only. CONCLUSION: These results suggested the TMZ/PSi NPs combined with HBO and PTT could be a potential therapeutic strategy for glioma.

Anions reversibly responsive luminescent nanocellulose hydrogels for cancer spheroids culture and release.

Artificial stimuli-responsive hydrogels that can mimic natural extracellular matrix for growth and release of cancer spheroids (CSs) have attracted much attention. However, such hydrogels still face a challenge in regulating CSs growth and controlled release as well as keeping CSs integrity. Herein, a new class of ClO-/SCN- reversibly responsive nanocellulose hydrogel with fluorescence on-off reporter is developed. Upon addition of ClO-, the gel network of nanocellulose hydrogel was destructed, accompanying by the fluorescent quenching. Notably, when introducing of SCN-, a red fluorescence filamentous hydrogel was recovered by coordination cross-linking. The hydrogel reforms in a completely reversible process through the regulation of ClO-/SCN-. Benefit from the above response features of the hydrogel, the growth of cancer spheroids (CSs) in the hydrogel and on demand release of CSs from the hydrogel could be easily achieved through ClO-/SCN- regulation. Importantly, the growth and release of CSs can be monitored in real time by fluorescence imaging. Overall, such design strategy based on ClO-/SCN--responsive fluorescent hydrogels provided a new type of multi-responsive hydrogels as main scaffolds for cancer research and cancer drug screening.

Drought losses in China might double between the 1.5 °C and 2.0 °C warming.

We project drought losses in China under global temperature increase of 1.5 °C and 2.0 °C, based on the Standardized Precipitation Evapotranspiration Index (SPEI) and the Palmer Drought Severity Index (PDSI), a cluster analysis method, and "intensity-loss rate" function. In contrast to earlier studies, to project the drought losses, we predict the regional gross domestic product under shared socioeconomic pathways instead of using a static socioeconomic scenario. We identify increasing precipitation and evapotranspiration pattern for the 1.5 °C and 2.0 °C global warming above the preindustrial at 2020-2039 and 2040-2059, respectively. With increasing drought intensity and areal coverage across China, drought losses will soar. The estimated loss in a sustainable development pathway at the 1.5 °C warming level increases 10-fold in comparison with the reference period 1986-2005 and nearly threefold relative to the interval 2006-2015. However, limiting the temperature increase to 1.5 °C can reduce the annual drought losses in China by several tens of billions of US dollars, compared with the 2.0 °C warming.

Hyperbaric oxygen as an adjuvant to temozolomide nanoparticle inhibits glioma growth by inducing G2/M phase arrest.

AIM: To study the effects of combinational treatment of hyperbaric oxygen (HBO) and nanotemozolomide in glioma. MATERIALS & METHODS: Temozolomide (TMZ)-loaded porous silicon nanoparticles (TMZ/PSi NPs) were prepared. In vitro and in vivo evaluations were performed. RESULTS: The cell uptake of TMZ/PSi NPs could be tracked by autofluorescence of porous silicon. The concentration of oxygen in tumor was improved and the antitumor rate was increased to 84.2% in the TMZ/PSi NPs combined with HBO group. The viability of hypoxia-induced glioma C6 cells was decreased and cell cycle was arrested at G2/M phase in response to TMZ/PSi NPs treatment with HBO compared with continuous treatment with hypoxia. CONCLUSION: The combinational treatment of TMZ/PSi NPs and HBO could be a promising therapeutic strategy for glioma.

Co-delivery nanoparticle to overcome metastasis promoted by insufficient chemotherapy.

Heterogeneous distribution of drug inside tumor is ubiquitous, causing regional insufficient chemotherapy, which might be the hotbed for drug resistance, tumor cell repopulation and metastasis. Herein, we verify, for the first time, that heterogeneous drug distribution induced insufficient chemotherapy would accelerate the process of epithelial mesenchymal transition (EMT), consequently resulting in the promotion of tumor metastasis. To eliminate the insufficient chemotherapy promoted metastasis, we conceived a co-delivery strategy by hydroxyethyl starch-polylactide (HES-PLA) nanoparticle, in which DOX and TGF-ß receptor inhibitor, LY2157299 (LY), were administered together. In vitro and in vivo studies demonstrate that this co-delivery strategy can simultaneously suppress primary tumor and distant metastasis. Further study on immunofluorescence images of primary tumor verifies that low dose of DOX exasperates the EMT process, whereas the co-delivery nanoparticle can dramatically inhibit the progression of EMT. We reveal the impact of heterogeneous drug distribution on tumor metastasis and develop an effective co-delivery strategy to suppress the metastasis, providing guidance for clinical cancer therapy.

Photocatalysis-Based Nanoprobes Using Noble Metal-Semiconductor Heterostructure for Visible Light-Driven in Vivo Detection of Mercury.

The development of sensitive and reliable methods to monitor the presence of mercuric ions in cells and organisms is of great importance to biological research and biomedical applications. In this work, we propose a strategy to construct a solar-driven nanoprobe using a 3D Au@MoS2 heterostructure as a photocatalyst and rhodamine B (RB) as a fluorescent and color change reporter molecule for monitoring Hg2+ in living cells and animals. The sensing mechanism is based on the photoinduced electron formation of gold amalgam in the 3D Au@MoS2 heterostructure under visible light illumination. This formation is able to remarkably inhibit the photocatalytic activity of the heterostructure toward RB decomposition. As a result, "OFF-ON" fluorescence and color change are produced. Such characteristics enable this new sensing platform to sensitively and selectively detect Hg2+ in water by fluorescence and colorimetric methods. The detection limits of the fluorescence assay and colorimetric assay are 0.22 and 0.038 nM for Hg2+, respectively; these values are well below the acceptable limits in drinking water standards (10 nM). For the first time, such photocatalysis-based sensing platform is successfully used to monitor Hg2+ in live cells and mice. Our work therefore opens a promising photocatalysis-based analysis methodology for highly sensitive and selective in vivo Hg2+ bioimaging studies.

SCRaMbLE generates designed combinatorial stochastic diversity in synthetic chromosomes.

Synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) generates combinatorial genomic diversity through rearrangements at designed recombinase sites. We applied SCRaMbLE to yeast synthetic chromosome arm synIXR (43 recombinase sites) and then used a computational pipeline to infer or unscramble the sequence of recombinations that created the observed genomes. Deep sequencing of 64 synIXR SCRaMbLE strains revealed 156 deletions, 89 inversions, 94 duplications, and 55 additional complex rearrangements; several duplications are consistent with a double rolling circle mechanism. Every SCRaMbLE strain was unique, validating the capability of SCRaMbLE to explore a diverse space of genomes. Rearrangements occurred exclusively at designed loxPsym sites, with no significant evidence for ectopic rearrangements or mutations involving synthetic regions, the 99% nonsynthetic nuclear genome, or the mitochondrial genome. Deletion frequencies identified genes required for viability or fast growth. Replacement of 3' UTR by non-UTR sequence had surprisingly little effect on fitness. SCRaMbLE generates genome diversity in designated regions, reveals fitness constraints, and should scale to simultaneous evolution of multiple synthetic chromosomes.

Changes and Relationships of Climatic and Hydrological Droughts in the Jialing River Basin, China.

The comprehensive assessment of climatic and hydrological droughts in terms of their temporal and spatial evolutions is very important for water resources management and social development in the basin scale. To study the spatial and temporal changes of climatic and hydrological droughts and the relationships between them, the SPEI and SDI are adopted to assess the changes and the correlations of climatic and hydrological droughts by selecting the Jialing River basin, China as the research area. The SPEI and SDI at different time scales are assessed both at the entire Jialing River basin and at the regional levels of the three sub basins. The results show that the SPEI and SDI are very suitable for assessing the changes and relationships of climatic and hydrological droughts in large basins. Based on the assessment, for the Jialing River basin, climatic and hydrological droughts have the increasing tendency during recent several decades, and the increasing trend of climatic droughts is significant or extremely significant in the western and northern basin, while hydrological drought has a less significant increasing trend. Additionally, climatic and hydrological droughts tend to increase in the next few years. The results also show that on short time scales, climatic droughts have one or two months lag impact on hydrological droughts in the north-west area of the basin, and have one month lag impact in south-east area of the basin. The assessment of climatic and hydrological droughts based on the SPEI and SDI could be very useful for water resources management and climate change adaptation at large basin scale.

Genomic signatures of near-extinction and rebirth of the crested ibis and other endangered bird species.

BACKGROUND: Nearly one-quarter of all avian species is either threatened or nearly threatened. Of these, 73 species are currently being rescued from going extinct in wildlife sanctuaries. One of the previously most critically-endangered is the crested ibis, Nipponia nippon. Once widespread across North-East Asia, by 1981 only seven individuals from two breeding pairs remained in the wild. The recovering crested ibis populations thus provide an excellent example for conservation genomics since every individual bird has been recruited for genomic and demographic studies. RESULTS: Using high-quality genome sequences of multiple crested ibis individuals, its thriving co-habitant, the little egret, Egretta garzetta, and the recently sequenced genomes of 41 other avian species that are under various degrees of survival threats, including the bald eagle, we carry out comparative analyses for genomic signatures of near extinction events in association with environmental and behavioral attributes of species. We confirm that both loss of genetic diversity and enrichment of deleterious mutations of protein-coding genes contribute to the major genetic defects of the endangered species. We further identify that genetic inbreeding and loss-of-function genes in the crested ibis may all constitute genetic susceptibility to other factors including long-term climate change, over-hunting, and agrochemical overuse. We also establish a genome-wide DNA identification platform for molecular breeding and conservation practices, to facilitate sustainable recovery of endangered species. CONCLUSIONS: These findings demonstrate common genomic signatures of population decline across avian species and pave a way for further effort in saving endangered species and enhancing conservation genomic efforts.