Metatranscriptomics revealed the molecular characterization of circulating enterovirus strains causing aseptic meningitis in children in Wuxi, China.

Enteroviruses are major etiological agents of aseptic meningitis globally, however information on circulating enterovirus types associated with this disease in Wuxi, China is limited. In this study, cerebrospinal fluid samples were collected from 20 pediatric aseptic meningitis cases in a Wuxi hospital in 2020 and subjected to metagenomic analysis to detect pathogens. Enterovirus B was detected in 9 cases, including 7 echovirus 18 (E18) and 2 echovirus 11 (E11) strains. The E18 strains exhibited 87.5-98.2% nucleotide identity and phylogenetically clustered with other China E18 strains, while the E11 strains showed 97.59% identity and clustered within the D5 subgroup along with other China E11 strains. One E18 strain was identified as a novel recombinants with a distinct recombination breakpoint within 3D gene. These findings expand knowledge on enteroviruses associated with pediatric aseptic meningitis in Wuxi, and highlight the circulation of genetically diverse E18 and E11 strains, including novel E18 recombinants. Characterization of enterovirus diversity by metagenomic analysis is important for molecular diagnosis and epidemiological tracking of aseptic meningitis cases. Continued surveillance of circulating enterovirus strains in Wuxi that may cause future outbreaks is warranted.

Hypoxia induces mitochondrial protein lactylation to limit oxidative phosphorylation.

Oxidative phosphorylation (OXPHOS) consumes oxygen to produce ATP. However, the mechanism that balances OXPHOS activity and intracellular oxygen availability remains elusive. Here, we report that mitochondrial protein lactylation is induced by intracellular hypoxia to constrain OXPHOS. We show that mitochondrial alanyl-tRNA synthetase (AARS2) is a protein lysine lactyltransferase, whose proteasomal degradation is enhanced by proline 377 hydroxylation catalyzed by the oxygen-sensing hydroxylase PHD2. Hypoxia induces AARS2 accumulation to lactylate PDHA1 lysine 336 in the pyruvate dehydrogenase complex and carnitine palmitoyltransferase 2 (CPT2) lysine 457/8, inactivating both enzymes and inhibiting OXPHOS by limiting acetyl-CoA influx from pyruvate and fatty acid oxidation, respectively. PDHA1 and CPT2 lactylation can be reversed by SIRT3 to activate OXPHOS. In mouse muscle cells, lactylation is induced by lactate oxidation-induced intracellular hypoxia during exercise to constrain high-intensity endurance running exhaustion time, which can be increased or decreased by decreasing or increasing lactylation levels, respectively. Our results reveal that mitochondrial protein lactylation integrates intracellular hypoxia and lactate signals to regulate OXPHOS.

Minimal adverse outcomes of postnatal cytomegalovirus infection in term or moderate and late preterm infants.

Objective: The aim of study was to investigate at what extent breastfeeding and vaginal delivery can increase mother-to-child transmission of cytomegalovirus (CMV) and to observe the clinical outcomes of postnatal infection in term or moderate and late preterm infants. Methods: In this retrospective study of prospectively collected clinical data and serum samples, during 2012-2015, 380 women with CMV IgG positive/IgM negative and their 384 infants (4 twin pairs) with gestational age ≥32 weeks were included. CMV IgG and IgM were measured with enzyme-linked immunosorbent assay. Results: Of 384 infants followed up at 10.2 ± 2.3 months age, 177 (46.1%) were defined with CMV infection based on the presence of higher CMV IgG levels than in their mothers. The infection rate in 190 breastfed infants was higher than in 194 formula-fed infants (62.6% vs. 29.9%, P < 0.001). Vaginally delivered infants (172) had higher CMV infection rate than 212 infants delivered by caesarean section (55.2% vs. 38.7%, P = 0.001). Compared with formula feeding and caesarean section, breastfeeding and vaginal delivery increased postnatal CMV infection respectively (OR = 3.801, 95% CI 2.474-5.840, P < 0.001; OR = 1.818, 95% CI 1.182-2.796, P = 0.007). Nevertheless, compared to uninfected infants, CMV-infected infants had comparable height and body weight and showed no adverse effect on the liver enzymes. Conclusion: Breastfeeding and vaginal delivery can increase postnatal CMV infection; however, the infection does not influence the growth of the term infants or preterm infants with gestational age ≥32 weeks. Thus, breastfeeding should be encouraged in these infants regardless of maternal CMV IgG status.

Towards quantum simulation of Sachdev-Ye-Kitaev model.

We study a simplified version of the Sachdev-Ye-Kitaev (SYK) model with real interactions by exact diagonalization. Instead of satisfying a continuous Gaussian distribution, the interaction strengths are assumed to be chosen from discrete values with a finite separation. A quantum phase transition from a chaotic state to an integrable state is observed by increasing the discrete separation. Below the critical value, the discrete model can well reproduce various physical quantities of the original SYK model, including the volume law of the ground-state entanglement, level distribution, thermodynamic entropy, and out-of-time-order correlation (OTOC) functions. For systems of size up to N=20, we find that the transition point increases with system size, indicating that a relatively weak randomness of interaction can stabilize the chaotic phase. Our findings significantly relax the stringent conditions for the realization of SYK model, and can reduce the complexity of various experimental proposals down to realistic ranges.