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Family communication patterns and adolescent depressive symptoms: sequential mediating effects of hedonic capacity and anger expression.

OBJECTIVE: Depression is increasingly prevalent among adolescents, highlighting the need to explore its underlying developmental mechanisms to inform effective prevention. This study examined how different family communication patterns longitudinally impact adolescent depressive symptoms, with a focus on the mediating roles of diminished hedonic capacity and anger expression. METHOD: A total of 729 Chinese adolescents from five high schools participated in this two-wave longitudinal study over a six-month period. Participants completed the Family Communication Patterns Scale (FCPS), the Children's Depression Inventory (CDI), the Anhedonia Scale for Adolescents (ASA), and the Children's Inventory of Anger (ChIA). Mediation analyses were conducted using Hayes' PROCESS macro, alongside cross-lagged panel analyses to explore longitudinal effect. RESULTS: Cross-sectional analyses indicated that diminished hedonic capacity and anger experience sequentially mediated the relationship between family communication patterns and adolescent depressive symptoms. Specifically, this mediating effect existed for conversation orientation in junior high school students and female senior high school students, as well as for conformity orientation among female junior and senior high school students. In addition, longitudinal analyses revealed that diminished hedonic capacity mediated the associations at Wave 2. CONCLUSION: Our findings suggest that enhanced hedonic capacity and reduced anger expression may play a key role in the relationship between family communication patterns and adolescent depression, and hedonic capacity should be prioritized in practical interventions. These results support the potential value of interventions that promote positive family communication patterns as a means of mitigating adolescent depression, particularly for families with daughters.

anger expression

Insertion of CG repeats and 3' terminus overhangs drive B-to-Z transition: A case study with NF-κB bearing DNA nanostructures.

Z-DNA, a non-canonical helical structure of DNA plays a vital role in various biological processes, including transcription and genomic stability. Though low concentration of trivalent cations is known to induce B-Z transition, the effect of short CG repeats, overhangs sequences, loop length and order of nucleotides on Z-DNA formation in larger DNA is utterly unknown. Earlier, a series of self-assembled branched DNA (bDNA) nanostructures having 5T in the loop are reported to be resistant to B-to-Z DNA transition irrespective of the overhang sequences. Since the presence of alternative purine/pyrimidine sequences and direction of oligonucleotides play a vital role during replication and transcription, we hypothesize that the insertion of a small number of CG repeats, or a change in direction of overhang sequences may influence the B-to-Z DNA transition. Here, we show that Z-DNA formation was induced by inserting CG repeats into bDNA structures that were previously resistant to B-Z transition. Moreover, B-Z transition was also observed when overhangs were introduced at the 3' terminus. The generality of the approach of B-Z transition was demonstrated in a series of bDNA structures including the bDNA having NF-kβ sequences. Different dye binding experiments suggest the formation of Z-DNA in bDNA having overhangs at the 3' terminus against the control of bDNA with 5' overhangs. Interestingly, the melting temperature (Tm) was substantially reduced to 55 °C in the Z-DNA as compared to the LaCl3-induced condensed DNA having Tm of 77 °C. Fluorescence study also supports the presence of minor groove in Z-DNA which binds Hoechst. ITC indicates an entropy- and enthalpy-driven favorable binding between lanthanide cations and bDNA. Thus, the present study establishes a synthetic bDNA nanotechnology platform for systematically investigating how local sequence architecture, including the insertion of CG repeats, loop length, and overhang orientation influences B-to-Z conformational switching under controlled experimental conditions.

B-Z transition

Multidimensional Protein Corona Analysis Toward Predictive Nano-Bio Interface Design.

Nanoparticles entering biological fluids are rapidly coated by proteins and other biomolecules, converting their synthetic surfaces into biologically active nano-bio interfaces. These coronas regulate colloidal stability, immune recognition, cellular uptake, biodistribution, pharmacokinetics, cargo delivery, and toxicity. Yet a protein list obtained by mass spectrometry captures only part of this interface. Corona identity and function are also shaped by protein organization, binding stability, exchange dynamics, conformational changes, and molecular accessibility. Here, we discuss recent progress in protein corona isolation and analysis from a question-oriented analytical perspective, with emphasis on how centrifugation, magnetic recovery, affinity- or chemistry-enabled capture, chromatography, filtration, and field-flow fractionation (FFF) influence the fidelity, integrity, and comparability of recovered coronas. We then examine how proteomic profiling can be integrated with binding measurements, interfacial structural analysis and functional validation to distinguish descriptive corona signatures from biologically meaningful mechanisms. We further consider how biofluid composition, disease state, tissue interfaces and cellular environments remodel corona identity, presentation, and bioactivity. Finally, we argue that standardized reporting, computational modeling, and AI-enabled approaches are essential for converting protein corona datasets into reproducible and predictive knowledge that can guide the design of drug delivery systems and precision nanomedicines.

Protein Corona

A structural bridge between dengue virus tandem xrRNAs facilitates coordination of exonuclease resistance.

Orthoflavivirus RNA genomes resist host 5'-3' exoribonucleases to produce subgenomic flaviviral RNAs (sfRNAs). This resistance is conferred by exoribonuclease-resistant RNA (xrRNA) structures within the viral 3' untranslated region that often occur in tandem, and whose function can be coupled. In dengue virus serotype 2 (DENV2), this coupling results in changing patterns of sfRNA identity and abundance associated with the ability of the virus to adapt to host vs. vector infections. The physical basis of this coupling was unknown. Using a combination of virology, biochemistry, bioinformatics, structural biology, and biophysics, we explored the structural and sequence determinants of tandem xrRNA coupling in DENV2. We discovered that the spatial proximity, order, and structural integrity of the tandem xrRNAs are all important for coupling. Furthermore, an unpaired A-rich linker that lies between the two xrRNAs is essential in stabilizing a specific structure that correlates to coupling. This A-rich sequence likely forms tertiary contacts with an adjacent stem-loop structure to form a physical bridge between the two xrRNAs, a finding that is supported by a mid-resolution cryo-electron microscopy (cryo-EM) map of the DENV2 tandem xrRNAs. Disruption of the structure of this bridge by mutation changes the relative orientation or spacing between the tandem xrRNAs, which is correlated to their functional coupling. These findings help provide an explanation for the coupling between tandem xrRNAs, suggesting a new mechanistic hypothesis in which the two tandem xrRNAs can simultaneously encounter Xrn1.IMPORTANCEDengue virus (DENV) generates non-coding subgenomic flaviviral RNAs (sfRNAs) that affect several cellular pathways and are important for successful infection. These sfRNAs are formed by structured RNA elements in the viral genome called exoribonuclease-resistant RNAs (xrRNAs), which fold into a distinct three-dimensional topology to block degradation by host cell exoribonucleases and often occur in tandem. Specific patterns of sfRNAs made during infection are important for host vs. vector fitness, and in DENV2, this pattern depends on functional coupling between tandem xrRNAs. However, the source of this functional coupling was unknown. We determined that an unpaired A-rich linker between the tandem xrRNAs is necessary for creating a structural bridge between the tandem xrRNAs. This bridge appears to favor a specific orientation between the tandem xrRNAs that is correlated to coupling and therefore to the patterns and relative abundance of sfRNAs produced during infection.

Dengue Virus

Structural basis of β-arrestin coupling and transducer selectivity in PAC1R.

The pituitary adenylate cyclase-activating polypeptide receptor (PAC1R) is a class B G protein-coupled receptor (GPCR) that engages both G proteins and β-arrestins to mediate diverse signaling responses, yet how PAC1R adopts distinct intracellular conformations to achieve this transducer selectivity remains poorly understood. Here, we report the cryo-electron microscopy structure of PAC1R in complex with β-arrestin 1 (βarr1), revealing a core-engaged conformation. Comparison with the Gs-bound PAC1R structure shows that βarr1 engagement is associated with remodeling of the intracellular transmembrane bundle, including TM5 reorientation and inward movement of TM6, resulting in a receptor core geometry distinct from that of the G protein-bound state. Comparison with the βarr1-bound parathyroid hormone receptor 1 (PTH1R) structure further reveals both conserved and receptor-specific features of βarr1 engagement. Although outward displacement of the TM5 cytoplasmic end is observed in both PAC1R-βarr1 and PTH1R-βarr1 complexes, its specific direction and the resulting TM5-TM6 rearrangements differ between receptors, correlating with distinct βarr1 finger loop orientations within the receptor core. Together, these findings suggest that β-arrestin core engagement by class B GPCRs is accompanied by receptor-specific intracellular remodeling that may contribute to transducer selectivity in PAC1R.

Class B GPCR

The influence of 10n and 10n+5 linker lengths on chromatin fiber topologies explored by mesoscale modeling.

The structural organization of chromatin is intricately influenced by the length of linker DNA connecting nucleosomes. Some studies have suggested preferred linker lengths of 10n and 10n+5 base pairs (bp) (n = integer). Because these lengths dictate the rotational orientation of successive nucleosomes in the fiber axis, they can markedly affect chromatin fiber compaction and topology. Using a refined mesoscale chromatin model with 5-bp resolution, we investigate the influence of linker DNA periodicity, linker histone density, salt concentration, and starting fiber topology on chromatin architecture for regular fibers versus "life-like" fibers, the latter with irregular spacing between nucleosomes. Our results reveal that regular fibers with 10n linkers exhibit compact zigzag configurations, whereas 10n+5 linkers generate more open and flexible structures. However, these effects are pronounced only for short linker lengths, as longer linkers are more heterogeneous. Moreover, increased linker histone density further enhances compaction for long linker lengths, and lower salt concentration modifies chromatin topologies, diminishing periodicity-driven effects. In addition, any periodicity effect in tightly packed solenoid configurations is much less pronounced. All these trends for regular fibers are reduced in life-like fibers with irregularly spaced nucleosomes, despite having the same average spacing. Moreover, the trend details depend highly on specific features of the fiber architecture as designed in experiments and simulations. Overall, our study highlights how reported differences depend on modeling details and emphasizes the role of linker DNA length in regulating chromatin fiber architecture and its potential implications for genome accessibility and expression.

Chromatin