RNA-RNA Interactomes of ProQ and Hfq Reveal Overlapping and Competing Roles.

Base pairing RNAs modulate gene expression in all studied organisms. In many bacteria, the base pairing between most small regulatory RNAs (sRNAs) and their targets is mediated by the Hfq RNA chaperone. However, recent studies have shown FinO-domain proteins also bind sRNAs. To examine the global contribution of the FinO-domain ProQ protein in Escherichia coli, we carried out RIL-seq to identify RNA pairs bound to this protein. The RNA-RNA interactome for ProQ contains hundreds of pairs. Intriguingly, a significant fraction of the ProQ-bound RNA pairs are also found associated with Hfq, indicating overlapping, complementary, or competing roles for the two proteins. Characterization of one novel RNA pair bound by both chaperones revealed that while Hfq is required for RNA sponge-mediated downregulation of the sRNA, ProQ can inhibit this regulation. Overall, our results uncover increased complexity in RNA regulatory networks involving RNA chaperone proteins, RNases, sRNAs, and mRNAs.

An acetyltranferase moonlights as a regulator of the RNA binding repertoire of the RNA chaperone Hfq in Escherichia coli.

Bacterial small RNAs (sRNAs) regulate gene expression by base-pairing with their target mRNAs. In Escherichia coli and many other bacteria, this process is dependent on the RNA chaperone Hfq, a mediator for sRNA-mRNA annealing. YhbS (renamed here as HqbA), a putative Gcn5-related N-acetyltransferase (GNAT), was previously identified as a silencer of sRNA signaling in a genomic library screen. Here, we studied how HqbA regulates sRNA signaling and investigated its physiological roles in modulating Hfq activity. Using fluorescent reporter assays, we found that HqbA overproduction suppressed all tested Hfq-dependent sRNA signaling. Direct interaction between HqbA and Hfq was demonstrated both in vivo and in vitro, and mutants that blocked the interaction interfered with HqbA suppression of Hfq. However, an acetylation-deficient HqbA mutant still disrupted sRNA signaling, and HqbA interacted with Hfq at a site far from the active site. This suggests that HqbA may be bifunctional, with separate roles for regulating via Hfq interaction and for acetylation of undefined substrates. Gel shift assays revealed that HqbA strongly reduced the interaction between the Hfq distal face and low-affinity RNAs but not high-affinity RNAs. Comparative RNA immunoprecipitation of Hfq and sequencing showed enrichment of two tRNA precursors, metZWV and proM, by Hfq in mutants that lost the HqbA-Hfq interaction. Our results suggest that HqbA provides a level of quality control for Hfq by competing with low-affinity RNA binders.

Dual-function AzuCR RNA modulates carbon metabolism.

SignificanceWhile most small, regulatory RNAs are thought to be "noncoding," a few have been found to also encode a small protein. Here we describe a 164-nucleotide RNA that encodes a 28-amino acid, amphipathic protein, which interacts with aerobic glycerol-3-phosphate dehydrogenase and increases dehydrogenase activity but also base pairs with two mRNAs to reduce expression. The coding and base-pairing sequences overlap, and the two regulatory functions compete.

Kerr nonlinearity assisted magnetically induced transparency in cavity magnon polaritons.

We investigate optical transmission in cavity magnon polaritons and discover a complex multi-window magnetically induced transparency and a bistability with magnetic and optical characteristics. With the regulation of Kerr nonlinear effects and driven fields, a complex multi-window resonant transmission with fast and slow light effects appears, which includes transparency and absorption windows. The magnetically induced transparency and absorption can be explained by the destructive and constructive interference between different excitation pathways. Moreover, we demonstrate the bistability of magnons and photons with a hysteresis loop, where magnetic and optical bistabilities can induce and control each other. Our results pave a new way, to the best of our knowledge, for implementing a room-temperature multiband quantum memory.

Research progress on ion channels and their molecular regulatory mechanisms in the human sperm flagellum.

The ion channels in sperm tail play an important role in triggering key physiological reactions, e.g., progressive motility, hyperactivation, required for successful fertilization. Among them, CatSper and KSper have been shown to be important ion channels for the transport of Ca2+ and K+ . Moreover, the voltage-gated proton channel Hv1, the sperm-specific sodium-hydrogen exchanger (sNHE), the epithelial sodium channel (ENaC), members of the temperature-sensitive TRP channel family, and the cystic fibrosis transmembrane regulator (CFTR) are also found in the flagellum. This review focuses on the latest advances in ion channels located at the flagellum, describes how they affect sperm physiological function, and summarizes some primary mutual regulation mechanism between ion channels, including PH, membrane potential, and cAMP. These ion channels may be promising targets for clinical application in infertility.

Multiple in vivo roles for the C-terminal domain of the RNA chaperone Hfq.

Hfq, a bacterial RNA chaperone, stabilizes small regulatory RNAs (sRNAs) and facilitates sRNA base-pairing with target mRNAs. Hfq has a conserved N-terminal domain and a poorly conserved disordered C-terminal domain (CTD). In a transcriptome-wide examination of the effects of a chromosomal CTD deletion (Hfq1-65), the Escherichia coli mutant was most defective for the accumulation of sRNAs that bind the proximal and distal faces of Hfq (Class II sRNAs), but other sRNAs also were affected. There were only modest effects on the levels of mRNAs, suggesting little disruption of sRNA-dependent regulation. However, cells expressing Hfq lacking the CTD in combination with a weak distal face mutation were defective for the function of the Class II sRNA ChiX and repression of mutS, both dependent upon distal face RNA binding. Loss of the region between amino acids 66-72 was critical for this defect. The CTD region beyond amino acid 72 was not necessary for distal face-dependent regulation, but was needed for functions associated with the Hfq rim, seen most clearly in combination with a rim mutant. Our results suggest that the C-terminus collaborates in various ways with different binding faces of Hfq, leading to distinct outcomes for individual sRNAs.

Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas.

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective ß-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.

Utility of the capability, opportunity, and motivation behaviour (COM-B) model in explaining the negative association between pre-pregnancy body mass index and exclusive breastfeeding at six weeks postpartum.

The mechanisms underlying the negative associations between pre-pregnancy body mass index (BMI) and exclusive breastfeeding remain poorly understood. Thus, the study aimed to determine whether the negative associations between high pre-pregnancy BMI and exclusive breastfeeding at six weeks postpartum are mediated by components of the capability, opportunity, and motivation behaviour (COM-B) model. In this prospective observational study, we assigned 360 primiparous women to a pre-pregnancy overweight/obese group (n = 180) and a normal-BMI group (n = 180). A structural equation model was designed to study how capabilities (onset of lactogenesis II, perceived milk supply, breastfeeding knowledge, and postpartum depression), opportunities (pro-breastfeeding hospital practices, social influence, social support), and motivations (breastfeeding intention, breastfeeding self-efficacy, and attitudes towards breastfeeding) affected exclusive breastfeeding at six weeks postpartum in groups of women with different pre-pregnancy BMIs. In all, 342 participants (95.0%) possessed complete data. Women with high pre-pregnancy BMI were less likely to exclusively breastfeed at six weeks postpartum than women with a normal BMI were. We observed a significant negative direct effect of high pre-pregnancy BMI on exclusive breastfeeding at six weeks postpartum and a significantly negative indirect effect of high pre-pregnancy BMI via the explanatory mediating variables of capabilities (onset of lactogenesis II, perceived milk supply, and breastfeeding knowledge) and motivations (breastfeeding self-efficacy) on exclusive breastfeeding at six weeks postpartum. Our findings support certain capabilities (onset of lactogenesis II, perceived milk supply, and breastfeeding knowledge) and motivations (breastfeeding self-efficacy), partially explaining the negative association between high pre-pregnancy BMI and exclusive breastfeeding outcome. We suggest that interventions aimed at promoting exclusive breastfeeding among women with high pre-pregnancy BMI should address the capacity and motivation factors specific to this population.

Association Between Social Networking Site Use Intensity and Depression Among Chinese Pregnant Women: Cross-sectional Study.

BACKGROUND: Despite extensive debates about the mental health impacts of the use of social networking sites (SNSs), including WeChat, the association and mechanisms between social interaction of WeChat use intensity and antenatal depression are unclear. OBJECTIVE: We aimed to test the mediating roles of upward social comparison on social interaction of WeChat and rumination in the association between social interaction of WeChat use intensity and antenatal depression. METHODS: A cross-sectional survey was conducted in four hospitals with the self-reported measures of social interaction of WeChat use intensity, upward social comparison on social interaction of WeChat, rumination, antenatal depression, and control variables. The mediation analysis was performed through Model 6 from the PROCESS macro 4.0 in SPSS 26. RESULTS: Results from 2661 participants showed that antenatal depression was unrelated to social interaction of WeChat use intensity (P=.54), but was significantly positively related to the attitude toward social interaction of WeChat (P=.01). The direct effect of attitude toward social interaction of WeChat use on antenatal depression was not statistically significant (ß=-.03, P=.05). The results supported an indirect relationship between attitude toward social interaction of WeChat use and antenatal depression via (1) upward social comparison on social interaction of WeChat (indirect effect value=0.04, 95% CI 0.03 to 0.06); (2) rumination (indirect effect value=-0.02, 95% CI -0.04 to -0.01); and (3) upward social comparison on social interaction of WeChat and rumination in sequence (indirect effect value=0.07, 95% CI 0.06 to 0.08). CONCLUSIONS: Our findings highlight the necessity of focusing on attitudes toward SNS use, and the importance of upward social comparison and rumination in understanding the effect of SNS use on antenatal depression.

Moroidin, a Cyclopeptide from the Seeds of Celosia cristata That Induces Apoptosis in A549 Human Lung Cancer Cells.

Interference of microtubule dynamics with tubulin-targeted drugs is a validated approach for cancer chemotherapy. Moroidin (1) is an Urticaceae-type cyclopeptide having a potent inhibitory effect on purified tubulin polymerization. So far, moroidin has not been chemically synthesized, and its effect on cancer cells remains unknown. Herein, the cyclopeptide moroidin was isolated and identified from the seeds of Celosia cristata, and a revised assignment of its NMR data was presented. For the first time, moroidin (1) was demonstrated as having cytotoxic effects for several cancer cells, especially A549 lung cancer cells. The cellular evidence obtained showed that moroidin disrupts microtubule polymerization and decreases ß-tubulin protein levels, but is not as potent as colchicine. Molecular docking indicated that 1 has a high binding potential to the vinca alkaloid site on tubulin. Moreover, moroidin arrested A549 cells in the G2/M phase and induced cell apoptosis. The intrinsic mitochondrial pathway and AKT were involved in the moroidin-induced cell apoptosis. In addition, moroidin (1) inhibited the migration and invasion of A549 cells at sublethal concentrations.