Morphological Transformation and Surface Engineering of Glycovesicles Driven by Bioinspired Hydrogen Bonds of Nucleobases.

Glycopolymer-based supramolecular glycoassemblies with signal-driven cascade morphological deformation and accessible surface engineering toward bioinspired functional glycomaterials have attracted much attention due to their diverse applications in fundamental and practical scenarios. Herein, we achieved the cascade morphological transformation and surface engineering of a nucleobase-containing polymeric glycovesicle through exploiting the bioinspired complementary multiple hydrogen bonds of complementary nucleobases. First, the synthesized thymine-containing glycopolymers (PGal30-b-PTAm249) are capable of self-assembling into well-defined glycovesicles. Several kinds of amphiphilic adenine-containing block copolymers with neutral, positive, and negative charges were synthesized to engineer the glycovesicles through the multiple hydrogen bonds between adenine and thymine. A cascade of morphological transformations from vesicles to ruptured vesicles with tails, to worm-like micelles, and finally to spherical micelles were observed via continuously adding the adenine-containing polymer into the thymine-containing glycovesicles. Furthermore, the surface charge properties of these glyconano-objects can be facilely regulated through incorporating various adenine-containing polymers. This work demonstrates the potential application of a unique bioinspired approach to precisely engineer the morphology and surface properties of glycovesicles for boosting their biological applications.

One-Pot Fabrication of Supramolecular Synthetic Protein Hydrogel with Tissue-like Integrated Dynamic Features.

Protein-incorporated soft networks have received remarkable attention during the past several years. They possess desirable properties similar to native tissues and organs and exhibit unique advantages in applications. However, fabrication of protein-based hydrogels usually suffers from complex protein mutation and modification or chemical synthesis, which limited the scale and yield of production. Meanwhile, the lack of rationally designed noncovalent interactions in networks may result in a deficiency of the dynamic features of materials. Therefore, a highly efficient method is needed to include supramolecular interactions into protein hydrogel to generate a highly dynamic hydrogel possessing integrated tissue-like properties. Here, we report the design and construction of native protein-based supramolecular synthetic protein hydrogels through a simple and efficient one-pot polymerization of acrylamide and ligand monomers in the presence of a ligand-binding protein. The supramolecular interactions in the network yield integrated dynamic properties, including remarkable stretchability over 10,000% of their original length, ultrafast self-healing abilities within 3-4 s, tissue-like fast stress relaxation, satisfactory ability of adhesion to different living and nonliving substrates, injectability, and high biocompatibility. Furthermore, this material demonstrated potential as a biosensor to monitor small finger movements. This strategy provides a new avenue for fabricating synthetic protein hydrogels with integrated features.

FA2H controls cool temperature sensing through modifying membrane sphingolipids in Drosophila.

Animals have evolved the ability to detect ambient temperatures, allowing them to search for optimal living environments. In search of the molecules responsible for cold-sensing, we examined a Gal4 insertion line in the larvae of Drosophila melanogaster from previous screening work, which has a specific expression pattern in the cooling cells (CCs). We identified that the targeted gene, fa2h, which encodes a fatty acid 2-hydroxylase, plays an important role in cool temperature sensing. We found that fa2h mutants exhibit defects in cool avoidance behavior and that this phenotype could be rescued by genetically re-introducing the wild-type version of FA2H in CCs but not the enzymatically disabled point mutation version. Calcium imaging data showed that CCs require fa2h to respond to cool temperature. Lipidomic analysis revealed that the 2-hydroxy sphingolipids content in the cell membranes diminished in fa2h mutants, resulting in increased fluidity of CC neuron membranes. Furthermore, in mammalian systems, we showed that FA2H strongly regulates the function of the TRPV4 channel in response to its agonist treatment and warming. Taken together, our study has uncovered a novel role of FA2H in temperature sensing and has provided new insights into the link between membrane lipid composition and the function of temperature-sensing ion channels.

Supportive care needs of women with gynaecological cancer: A systematic review and synthesis of qualitative studies.

AIMS: To synthesize existing qualitative research evidence on the supportive care needs of women with gynaecological cancer. DESIGN: Qualitative systematic review. DATA SOURCES: A comprehensive literature search was performed using nine databases (PubMed, Web of Science, PsycINFO, CINAHL, Embase, CBM, CNKI, VIP and WanFang) without restrictions regarding publication date; qualitative studies published in English or Chinese were included. Initial search in December 2021 and updated in October 2022. REVIEW METHODS: This study was conducted according to the Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidelines. The Critical Appraisal Skills Programme tool for qualitative research was used to assess the quality of all included papers. Finally, we adopted a thematic synthesis method, synthesized the main findings, and constructed themes. RESULTS: Eleven studies published between 2010 and 2021 were included in the review. Based on the thematic synthesis method, 10 descriptive themes were generated and five analytical themes were derived: psychological support, information support, social support, disease-specific symptom management and form of care. Women with gynaecological cancer expressed a desire for psychological support from empathetic healthcare professionals; information support included access to adequate and appropriate information, as well as communication and involvement; social support highlighted women's desire for peer support, family-related support and financial support; disease-specific symptom management described women's desire for support in coping with reproduction/sexual issues and form of care highlighted the need for continuity of care and holistic care. CONCLUSION: The supportive care needs of women with gynaecological cancer are multidimensional and complex. The future care practice should take women's needs as a starting point and provide ongoing holistic and individualized support. Healthcare providers' understanding and support of these needs are critical to improving women's clinical outcomes and quality of care. IMPACT: The present findings can help further develop supportive care programmes and make nursing interventions more targeted and effective. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Drosophila proboscis extension response and GCaMP imaging for assaying food appeal based on grittiness.

Fruit flies sense the features of food that are driven by particle size, including smoothness versus grittiness, by deflection of sensilla decorating the labellum, and md-L neurons. We describe adaptation of the Drosophila proboscis extension response assay, including steps to perform the taste tests and score behavioral responses, to determine preferences to foods with different sized particles. We also describe calcium imaging in GCaMP-expressing flies to assess the responses of md-L neurons to different levels of taste sensilla deflection. For complete details on the use and execution of this protocol, please refer to Li and Montell. (2021).

Mechanism for food texture preference based on grittiness.

An animal's decision to accept or reject a prospective food is based only, in part, on its chemical composition. Palatability is also greatly influenced by textural features including smoothness versus grittiness, which is influenced by particle sizes. Here, we demonstrate that Drosophila melanogaster is endowed with the ability to discriminate particle sizes in food and uses this information to decide whether a food is appealing. The decision depends on a mechanically activated channel, OSCA/TMEM63, which is conserved from plants to humans. We found that tmem63 is expressed in a multidendritic neuron (md-L) in the fly tongue. Loss of tmem63 impairs the activation of md-L by mechanical stimuli and the ability to choose food based on particle size. These findings reveal the first role for this evolutionarily conserved, mechanically activated TMEM63 channel in an animal and provide an explanation of how flies can sense and behaviorally respond to the texture of food provided by particles.

Temperature and Sweet Taste Integration in Drosophila.

Sugar-containing foods offered at cooler temperatures tend to be less appealing to many animals. However, the mechanism through which the gustatory system senses thermal input and integrates temperature and chemical signals to produce a given behavioral output is poorly understood. To study this fundamental problem, we used the fly, Drosophila melanogaster. We found that the palatability of sucrose is strongly reduced by modest cooling. Using Ca2+ imaging and electrophysiological recordings, we demonstrate that bitter gustatory receptor neurons (GRNs) and mechanosensory neurons (MSNs) are activated by slight cooling, although sugar neurons are insensitive to the same mild stimulus. We found that a rhodopsin, Rh6, is expressed and required in bitter GRNs for cool-induced suppression of sugar appeal. Our findings reveal that the palatability of sugary food is reduced by slightly cool temperatures through different sets of thermally activated neurons, one of which depends on a rhodopsin (Rh6) for cool sensation.

Selection and identification of novel peptides specifically targeting human cervical cancer.

Cervical cancer is the second most commonly diagnosed cancer and the third leading cause of cancer deaths among females in underdeveloped countries. This study aimed to identify several novel cervical cancer-specific targeting peptides (CSPs) to provide new methods for the effective diagnosis and treatment of cervical cancer. Peptide library screening in vivo was performed on human cervical cancer xenografts with Ph.D.™-12 and C7C phage display peptide libraries. Two specific peptide sequences (GDALFSVPLEVY and KQNLAEG), which were enriched in tumors, were screened, and respectively, named CSP-GD and CSP-KQ through three rounds of biopanning. The in vivo tumor-targeting ability of these peptides was identified by injecting them into mice with cervical cancer xenograft. CSPs were compounded and labeled with fluorescein isothiocyanate (FITC). The specificity and affinity of FITC-CSPs were evaluated in human cervical cancer cell lines and tissue microarrays in vitro by immunofluorescent staining. Results showed that FITC-CSP-GD and FITC-CSP-KQ evidently and specifically bound to the cell membrane and cytoplasm of SiHa, ME-180, and C-33A cells in vitro. In human cervical cancer tissue, FITC-CSP-GD and FITC-CSP-KQ strongly targeted human cervical adenocarcinoma and cervical squamous cell carcinoma tissues, respectively. A bright FITC signal was located mainly on the cell membrane and cytoplasm of tumor cells. In conclusion, the novel 12-residue peptide CSP-GD and 7-residue peptide CSP-KQ could specifically target human cervical cancer and may have the potential to be used in the diagnosis and targeted therapy of cervical cancer.

Cold-sensing regulates Drosophila growth through insulin-producing cells.

Across phyla, body size is linked to climate. For example, rearing fruit flies at lower temperatures results in bigger body sizes than those observed at higher temperatures. The underlying molecular basis of this effect is poorly understood. Here we provide evidence that the temperature-dependent regulation of Drosophila body size depends on a group of cold-sensing neurons and insulin-producing cells (IPCs). Electrically silencing IPCs completely abolishes the body size increase induced by cold temperature. IPCs are directly innervated by cold-sensing neurons. Stimulation of these cold-sensing neurons activates IPCs, promotes synthesis and secretion of Drosophila insulin-like peptides and induces a larger body size, mimicking the effects of rearing the flies in cold temperature. Taken together, these findings reveal a neuronal circuit that mediates the effects of low temperature on fly growth.