Nonsynchronous rotation of icy moon ice shells: The thermal wind perspective.

The ice shells of icy satellites have been hypothesized to undergo nonsynchronous rotation (NSR) under the influence of tidal torques and/or ocean currents. In this work, the author proposes that the thermal wind relationship can be combined with geostrophic turbulence theory to predict ocean stress onto the ice shell inside the tangent cylinder. High-resolution numerical simulations validate the prediction within a factor of 2. For the prediction to be valid, the rotation effect must dominate (Rossby number < 1), and the upper ocean should be stratified. The latter can be achieved with sufficiently large ice thickness variations [the threshold for Europa is O(100) m]. Using this framework, once the ice rheology, thickness variations and NSR rate are determined, one may be able to estimate the ocean overturn timescale and put constraints on the ocean vertical diffusivity or the heat flux originating from the silicate core.

The Hadley circulation in the Pangea era.

The Pangea era is an exceptional phase in Earth's history. It is characterized by its hothouse climate state and the latest supercontinent. Thus, it is expected that atmospheric circulation in the Pangea era was largely different from that of the modern world. Here, we study the Hadley circulation in the Pangea era and compare it with that of the present, by performing climate simulations. Our results show that the annual mean Hadley cells are about 20% and 45% weaker than that in the pre-industrial (PI) climate, and their poleward edges are about 2° wider in latitude. The austral winter cell is weakened by 27% and expanded by 2.6°, while the changes of the boreal winter cell are not significant. One distinctive feature is that the ascending branches of the boreal and austral winter cells shift to 23°S and 18°N, respectively, which are much more poleward than their present locations. Our analyses demonstrate that the weakening and widening of the Hadley circulation is due to increasing tropical and subtropical static stability, and that the poleward shifts of the ascending branches of the winter cells are associated with the geographic configuration of the supercontinent Pangea.

MADET: a Manually Curated Knowledge Base for Microbiomic Effects on Efficacy and Toxicity of Anticancer Treatments.

A plethora of studies have reported the associations between microbiota and multiple diseases, leading to the development of at least four databases to demonstrate microbiota-disease associations, i.e., gutMDisorder, mBodyMap, Gmrepo, and Amadis. Moreover, gut microbiota mediates drug efficacy and toxicity, whereas a comprehensive database to elucidate the microbiota-drug associations is lacking. Here, we report an open-access knowledge base, MADET (Microbiomics of Anticancer Drug Efficacy and Toxicity), which harbors 483 manually annotated microbiota-drug associations from 26 studies. MADET provides user-friendly functions allowing users to freely browse, search, and download data conveniently from the database. Users can customize their search filters in MADET using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy), and cancer type (e.g., lung cancer) with different types of experimental evidence of microbiota-drug association and causation. We have also enabled user submission to further enrich the data documented in MADET. The MADET database is freely available at https://www.madet.info. We anticipate that MADET will serve as a useful resource for a better understanding of microbiota-drug associations and facilitate the future development of novel biomarkers and live biotherapeutic products for anticancer therapies. IMPORTANCE Human microbiota plays an important role in mediating drug efficacy and toxicity in anticancer treatment. In this work, we developed a comprehensive online database, which documents over 480 microbiota-drug associations manually curated from 26 research articles. Users can conveniently browse, search, and download the data from the database. Search filters can be customized using different types of keywords, including bacterial name (e.g., Akkermansia muciniphila), anticancer treatment (e.g., anti-PD-1 therapy), and cancer type (e.g., lung cancer), with different types of experimental evidence of microbiota-drug association. We anticipate that this database will serve as a convenient platform for facilitating research on microbiota-drug associations, including the development of novel biomarkers for predicting drug outcomes as well as novel live biotherapeutic products for improving the outcomes of anticancer drugs.

Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer.

Anti-PD-1 immunotherapy has saved numerous lives of cancer patients; however, it only exerts efficacy in 10-15% of patients with colorectal cancer. Fecal microbiota transplantation (FMT) is a potential approach to improving the efficacy of anti-PD-1 therapy, whereas the detailed mechanisms and the applicability of this combination therapy remain unclear. In this study, we evaluated the synergistic effect of FMT with anti-PD-1 in curing colorectal tumor-bearing mice using a multi-omics approach. Mice treated with the combination therapy showed superior survival rate and tumor control, compared to the mice received anti-PD-1 therapy or FMT alone. Metagenomic analysis showed that composition of gut microbiota in tumor-bearing mice treated with anti-PD-1 therapy was remarkably altered through receiving FMT. Particularly, Bacteroides genus, including FMT-increased B. thetaiotaomicron, B. fragilis, and FMT-decreased B. ovatus might contribute to the enhanced efficacy of anti-PD-1 therapy. Furthermore, metabolomic analysis upon mouse plasma revealed several potential metabolites that upregulated after FMT, including punicic acid and aspirin, might promote the response to anti-PD-1 therapy via their immunomodulatory functions. This work broadens our understanding of the mechanism by which FMT improves the efficacy of anti-PD-1 therapy, which may contribute to the development of novel microbiota-based anti-cancer therapies.

Effects of microbiota on anticancer drugs: Current knowledge and potential applications.

Over the last decade, mounting evidence has revealed the key roles of gut microbiota in modulating the efficacy and toxicity of anticancer drugs, via mechanisms such as immunomodulation and microbial enzymatic degradation. As such, human microbiota presents as an exciting prospect for developing biomarkers for predicting treatment outcomes and interventional approaches for improving therapeutic effects. In this review, we analyze the current knowledge of the interplays among gut microorganisms, host responses and anticancer therapies (including cytotoxic chemotherapy and targeted therapy), with an emphasis on the immunomodulation function of microbiota which facilitates the efficacy of immune checkpoint inhibitors. Moreover, we propose several microbiota-modulating strategies including fecal microbiota transplantation and probiotics, which can be pursued to optimize the use and development of anticancer treatments. We anticipate that future clinical and preclinical studies will highlight the significance of human microbiome as a promising target towards precision medicine in cancer therapies. FUNDING: National Key Research and Development Program of China (2020YFA0907800), Shenzhen Science and Technology Innovation Program (KQTD20200820145822023) and National Natural Science Foundation of China (31900056 and 32000096).

How does salinity shape ocean circulation and ice geometry on Enceladus and other icy satellites?

Of profound astrobiological interest, Enceladus appears to have a global saline subsurface ocean, indicating water-rock reaction at present or in the past, an important mechanism in the moon's potential habitability. Here, we investigate how salinity and the partition of heat production between the silicate core and the ice shell affect ocean dynamics and the associated heat transport-a key factor determining equilibrium ice shell geometry. Assuming steady-state conditions, we show that the meridional overturning circulation of the ocean, driven by heat and salt exchange with the poleward-thinning ice shell, has opposing signs at very low and very high salinities. Regardless of these differing circulations, heat and fresh water converge toward the equator, where the ice is thick, acting to homogenize thickness variations. Among scenarios explored here, the pronounced ice thickness variations observed on Enceladus are most consistent with heating that is predominantly in the ice shell and a salinity of intermediate range.

Sociocultural-psychological predictors influencing parents' decision-making regarding HPV vaccination for their adolescent daughters in mainland China: An extended TPB model.

Introduction: Enhancing human papillomavirus (HPV) vaccine uptake rates to protect women's health is an important public health issue worldwide. China has taken a series of measures in recent years to promote HPV vaccination among school-aged girls, but the vaccine uptake rate remains low. Investigating the factors influencing vaccination-related decision-making of adolescent girls' parents is key to solving the problem. This study aimed to examine the influence of sociocultural-psychological predictors, including exposure to HPV-related stories (positive/negative), affective reactions (pride/regret), injunctive norms on the Internet and perceived moral obligation, on parents' HPV vaccination-related decision-making for girls aged 13-15 years in mainland China. Methods: A cross-sectional online survey using quota sampling was conducted in February 2022. Four hundred and five valid and qualified questionnaires were obtained. Partial least squares structural equation modeling was performed by SmartPLS 3 (i) to evaluate the reliability and validity of the measurement models of 11 constructs, and (ii) to test the effect relationships of the sociocultural-psychological predictors on parents' intention to vaccinate their daughters. Results: The study findings showed that parental decision-making regarding HPV vaccination was influenced by sociocultural and psychological factors. At the level of individual psychological factors, exposure to positive stories was significantly associated with perceived vaccine effectiveness (ß = 0.331, t = 8.448, p < 0.001), which strongly predicted the attitude toward vaccination (ß = 0.521, t = 8.133, p < 0.001); anticipated pride had more positive influence on vaccination-related decision-making (ß = 0.156, t = 2.176, p < 0.05) than anticipated regret. In terms of social influence, injunctive norms on the Internet had a significantly positive influence on vaccination intention (ß = 0.127, t = 2.382, p < 0.05), similar to descriptive norms (ß = 0.135, t = 3.358, p < 0.01). Perceived moral obligation at the cultural level was the strongest predictor of parental decision-making regarding HPV vaccination (ß = 0.193, t = 2.139, p < 0.05). Discussion: This study is the first in mainland China to systematically examine the sociocultural-psychological predictors of parents' decision-making to vaccinate their 13-15-year-old daughters against HPV. A new extended TPB model with a sociocultural-psychological approach was developed. This model can support the investigation of factors affecting HPV vaccine uptake rates in the mainland Chinese population and similar populations and help to understand the differences in vaccination-related decision-making between Eastern and Western cultures. Furthermore, the study provided some suggestions for HPV vaccination communication campaigns targeting adolescent girls' parents.

Spontaneous formation of geysers at only one pole on Enceladus's ice shell.

The ice shell on Enceladus, an icy moon of Saturn, exhibits strong asymmetry between the northern and southern hemispheres, with all known geysers concentrated over the south pole, even though the expected pattern of tidal forced deformation should be symmetric between the north and south poles. Using an idealized ice-evolution model, we demonstrate that this asymmetry may form spontaneously, without any noticeable a priori asymmetry (such as a giant impact or a monopole structure of geological activity), in contrast to previous studies. Infinitesimal asymmetry in the ice shell thickness due to random perturbations are found to be able to grow indefinitely, ending up significantly thinning the ice shell at one of the poles, thereby allowing fracture formation there. Necessary conditions to trigger this hemispheric symmetry-breaking mechanism are found analytically. A rule of thumb we find is that, for Galilean and Saturnian icy moons, the ice shell can undergo hemispheric symmetry breaking only if the mean shell thickness is around 10 to 30 km.