Different conformational dynamics of SNARE protein Ykt6 among yeast and mammals.

Ykt6 is one of the most conserved SNARE (N-ethylmaleimide-sensitive factor attachment protein receptor) proteins involved in multiple intracellular membrane trafficking processes. The membrane-anchoring function of Ykt6 has been elucidated to result from its conformational transition from a closed state to an open state. Two ways of regulating the conformational transition were proposed: the C-terminal lipidation and the phosphorylation at the SNARE core. Despite many aspects of common properties, Ykt6 displays differential cellular localizations and functional behaviors in different species, such as yeast, mammals, and worms. The structure-function relationship underlying these differences remains elusive. Here, we combined biochemical characterization, single-molecule FRET measurement, and molecular dynamics simulation to compare the conformational dynamics of yeast and rat Ykt6. Compared to rat Ykt6 (rYkt6), yeast Ykt6 (yYkt6) has more open conformations and could not bind dodecylphosphocholine that inhibits rYkt6 in the closed state. A point mutation T46L/Q57A was shown to be able to convert yYkt6 to a more closed and dodecylphosphocholine-bound state, where Leu46 contributes key hydrophobic interactions for the closed state. We also demonstrated that the phospho-mutation S174D could shift the conformation of rYkt6 to a more open state, but the corresponding mutation S176D in yYkt6 leads to a slightly more closed conformation. These observations shed light on the regulatory mechanism underlying the variations of Ykt6 functions across species.

Semi-Coherent Heterointerface Engineering via In Situ Phase Transition for Enhanced Sodium/Lithium-Ions Storage.

To improve ion transport kinetics and electronic conductivity between the different phases in sodium/lithium-ion battery (LIB/SIB) anodes, heterointerface engineering is considered as a promising strategy due to the strong built-in electric field. However, the lattice mismatch and defects in the interphase structure can lead to large grain boundary resistance, reducing the ion transport kinetics and electronic conductivity. Herein, monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface embedded in 3D connected Nitrogen-doped carbon yolk-shell matrix (Fe3Se4-Fe7Se8@NC) is obtained via an in situ phase transition process. Such semi-coherent heterointerface between Fe3Se4 and Fe7Se8 shows the matched interfacial lattice and strong built-in electric field, resulting in the low interface impedance and fast reaction kinetics. Moreover, the yolk-shell structure is designed to confine all monometallic selenide Fe3Se4-Fe7Se8 semi-coherent heterointerface nanoparticles, improving the structural stability and inhibiting the volume expansion effect. In particular, the 3D carbon bridge between multi-yolks shell structure improves the electronic conductivity and shortens the ion transport path. Therefore, the efficient reversible pseudocapacitance and electrochemical conversion reaction are enabled by the Fe3Se4-Fe7Se8@NC, leading to the high specific capacity of 439 mAh g-1 for SIB and 1010 mAh g-1 for LIB. This work provides a new strategy for constructing heterointerface of the anode for secondary batteries.

Sleep Quality in Patients With Ocular Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

OBJECTIVES: To investigate the sleep quality in patients with ocular graft-versus-host disease (oGVHD) compared with patients without oGVHD after allogeneic hematopoietic stem cell transplantation (alloHCT) and healthy controls. METHODS: This cross-sectional study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. Fifty healthy controls were also enrolled. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. Sleep quality was assessed by the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI). Poor sleep quality was defined as CPQSI score greater than 6. RESULTS: Patients after alloHCT demonstrated a significantly higher CPQSI score than those of controls {7.0 [interquartile range (IQR) 5.0-10.0] vs. 5.5 [IQR 4.8-7.0], P =0.002}, especially in the oGVHD subgroup (7.5 [IQR 5.0-11.0] vs. 6.0 [IQR 5.0-8.0], P =0.04) with nearly double prevalence of poor sleep quality (58 [62%] vs. 18 [37%], P =0.006). Poor sleep quality was strikingly correlated with oGVHD diagnosis (adjusted odds ratio [OR]=2.55, 95% confidence interval [CI]: 1.02-6.34, P =0.04) and systemic immunosuppressants (adjusted OR=2.61, 95% CI: 1.32-5.71, P =0.02). Among the ocular parameters, poor sleep quality was significantly associated with higher ICOGCG score (adjusted OR=1.20, 95% CI: 1.03-1.39, P =0.02) and lower tear film break-up time (adjusted OR=0.85, 95% CI: 0.74-0.99, P =0.05). CONCLUSIONS: Poor sleep quality was associated with an increased severity of oGVHD and tear film instability in the long-term alloHCT survivorship.

Vision-specific and cancer-specific quality of life in ocular graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

PURPOSE: To compare the vision-specific and cancer-specific quality of life (QOL) between patients with and without ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (alloHCT). METHODS: This cross-sectional observational study analyzed 142 patients after alloHCT including 94 patients with oGVHD and 48 without. oGVHD was diagnosed according to International Chronic Ocular GVHD Consensus Group (ICOGCG) criteria. QOL was assessed by using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). RESULTS: Compared with non-oGVHD patients, patients with oGVHD had worse vision-specific (NEI VFQ-25: 64.3 ± 20.3 vs. 77.6 ± 19.3, P < 0.001) and cancer-specific (EORTC QLQ-C30: 59.9 ± 20.3 vs. 67.4 ± 17.5, P = 0.03) QOL, as well as impaired cognitive function (72.7 ± 22.1 vs. 82.3 ± 19.0, P = 0.01). The vision-specific QOL was significantly correlated with ICOGCG score (ß = - 1.88, 95%CI: - 3.35 to - 0.41, P = 0.01) and post-alloHCT medical expense (ß = - 5.70, 95%CI: - 10.35 to - 1.05, P = 0.02), while cancer-specific QOL was strikingly correlated with post-alloHCT medical expense (ß = - 9.91, 95%CI: - 14.43 to - 5.39, P < 0.001), frequency of ophthalmic medication (ß = - 0.93, 95%CI: - 1.64 to - 0.21, P = 0.01), education (ß = - 6.97, 95%CI: - 13.31 to - 0.62, P = 0.03), and peripheral blood stem cell use (ß = - 6.42, 95%CI: - 12.59 to - 0.25, P = 0.04). CONCLUSIONS: Patients with oGVHD experienced significant impairment in both vision-specific and cancer-specific QOL including cognitive function when compared with those without after alloHCT. Multidimensional QOL assessment should be included in the long-term alloHCT survivorship care.

Dissecting the Protein Dynamics Coupled Ligand Binding with Kinetic Models and Single-Molecule FRET.

Protein-ligand interactions are crucial to many biological processes. Ligand binding and dissociation are the basic steps that allow proteins to function. Protein conformational dynamics have been shown to play important roles in ligand binding and dissociation. However, it is challenging to determine the ligand binding kinetics of dynamic proteins. Here, we undertook comprehensive single-molecule FRET (smFRET) measurements and kinetic model analysis to characterize the conformational dynamics coupled ligand binding of glutamine-binding protein (GlnBP). We showed that hinge and T118A mutations of GlnBP affect its conformational dynamics as well as the ligand binding affinity. Based on smFRET measurements, the kinetic model of ligand-GlnBP interactions was constructed. Using experimentally measured parameters, we solved the rate equations of the model and obtained the undetectable parameters of the model which allowed us to understand the ligand binding kinetics fully. Our results demonstrate that modulation of the conformational dynamics of GlnBP affects the ligand binding and dissociation rates. This study provides insights into the binding kinetics of ligands, which are related to the protein function itself.

Association between HLA-A gene polymorphism and early-onset preeclampsia in Chinese pregnant women early-onset.

BACKGROUND: Preeclampsia is an idiopathic disease during pregnancy. This study explores the correlation between HLA-A polymorphism and the onset of preeclampsia. METHODS: The Illumina HiSeq2500 sequencing platform was used to genotyping HLA-A allele in venous blood DNA of 50 preeclampsia pregnant women and 48 normal pregnant women and umbilical cord blood DNA of their children of Han nationality in China. The frequencies and distributions of alleles and genotypes among the mothers and their children were compared between the two groups. The differences of frequencies and distributions of genotypes were compared between the two groups according to the mothers' genotype compatibility. RESULTS: Twenty HLA-A alleles were detected in preeclampsia pregnant women and normal pregnant women; 21 HLA-A alleles were found in preeclampsia group fetuses and 22 HLA-A alleles in control group fetuses. There was no statistical difference in the HLA-A genes' frequency between the two groups of pregnant women and their fetuses. When the sharing antigen was 1, the number of maternal-fetal pairs in the preeclampsia group was more than that in the control group; the difference was statistically significant (P < 0.05). The frequency of neither mother nor fetus carrying the HLA-A * 24: 02 gene in the preeclampsia group was significantly lower than that in the control group (P < 0.05). HLA-A gene homozygosity in fetuses of early-onset preeclampsia group was substantially higher than that of the control group (P = 0.0148); there is no significant difference in pregnant women's genes homozygosity between early-onset preeclampsia group and the control group. CONCLUSIONS: HLA-A * 24: 02 may be a susceptibility gene for early preeclampsia.

Quantitative proteomic analysis of down syndrome biomarkers in maternal serum using isobaric tags for relative and absolute quantification (iTRAQ).

Prenatal diagnosis of Down syndrome (DS) is based on calculated risk involving maternal age, biochemical and ultrasonographic markers, and, more recently, cell-free DNA (cfDNA). The present study was designed to identify Down Syndrome biomarkers in maternal serum. We quantified the changes in maternal serum protein levels between 10 non-pregnant women, 10 pregnant women with healthy fetuses, and 10 pregnant women with DS fetuses using isobaric tags for relative and absolute quantification (iTRAQ). We subsequently conducted a Gene Ontology (GO) analysis. A total of 470 proteins were identified, 11 of which had significantly different serum levels between the DS fetus group and Healthy fetuses group. Our data shows the identified proteins may be relevant to DS and constitute potential DS biomarkers.

Lipidomic profiling of amniotic fluid and its application in fetal lung maturity prediction.

BACKGROUND: The pulmonary surfactant especially lipids in amniotic fluid can reflect the development stage of fetal lung maturity (FLM). However, the conventional lecithin/sphingomyelin (L/S) ratio method by thin layer chromatography (TLC) is insufficient and inconvenient for FLM prediction in clinical practice. METHODS: The amniotic fluid samples were collected from the pregnant women in labor or undergoing amniocentesis and analyzed for its lipid contents with the liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) method and the lamellar body count (LBC) method. To reveal the lipidomic profiling of different FLM stages, three groups of amniotic fluid samples including 8 from premature group (gestational week (GW) < 37), 10 from mature group (GW < 37), and 10 from mature group (GW > 38) were compared with the control group (n = 6) of 18 GWs separately. RESULTS: In the FLM prediction study, the sensitivity of the LC-HRMS method and LBC method was 91% and 73%, respectively; the specificity was 100% and 95%, respectively. The most significant metabolic pathway was linoleic acid metabolism between the premature group and the control group. Both glycerophospholipid metabolism and glycosylphosphatidylinositol-anchor biosynthesis were enriched in the mature groups. In search of potential FLM prediction markers in amniotic fluid, 8 phosphatidylcholines, 1 sphingomyelin, and 1 phosphatidylethanolamine were significantly increased in the mature groups compared with the premature group. CONCLUSION: An efficient LC-HRMS method for L/S ratio in predicting FLM was established. The linoleic acid metabolism may play an important role in the fetal lung development.

A revisit of the conformational dynamics of SNARE protein rYkt6.

N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins are involved in the fusion of vesicles with their target membranes. R-SNARE protein Ykt6 is one of the most conserved SNARE in eukaryotes. The conformational state of Ykt6 is regulated by the lipidations at its C-terminal motif. Previous studies show that the binding of dodecylphosphocholine (DPC) can stabilize a closed conformation of rat Ykt6 (rYkt6) and mimic the farnesylated rYkt6. Despite this model, the detailed conformational dynamics of Ykt6 is still unclear. Here, we combined smFRET and MD simulation to demonstrate that the un-lipidated rYkt6 adopts five major conformational states. DPC binding shifts the conformational distribution toward the more closed states. At the same time, there remain considerable fractions of open and semi-open conformations in the presence of DPC. These newly revealed dynamic features of rYkt6 are consistent with its unique functional diversity in neuronal cells.

Associations of breast milk adiponectin, leptin, insulin and ghrelin with maternal characteristics and early infant growth: a longitudinal study.

Breast milk (BM) hormones have been hypothesised as a nutritional link between maternal and infant metabolic health. This study aimed to evaluate hormone concentrations in BM of women with and without gestational diabetes mellitus (GDM), and the relationship between maternal factors, BM hormones and infant growth. We studied ninety-six nulliparous women with (n 48) and without GDM and their exclusively breastfed term singletons. Women with GDM received dietary therapy or insulin injection for euglycaemia during pregnancy. Hormone concentrations in BM, maternal BMI and infant growth were longitudinally evaluated on postnatal days 3, 42 and 90. Mothers with GDM had decreased concentrations of adiponectin (P colostrum<0·001; P mature-milk=0·009) and ghrelin (P colostrum=0·011; P mature-milk<0·001) and increased concentration of insulin in BM (P colostrum=0·047; P mature-milk=0·021). Maternal BMI was positively associated with adiponectin (ß=0·06; 95 % CI 0·02, 0·1; P=0·001), leptin (ß=0·16; 95 % CI 0·12, 0·2; P<0·001) and insulin concentrations (ß=0·06; 95 % CI 0·02, 0·1; P<0·001), and inversely associated with ghrelin concentration in BM (ß=-0·08; 95 % CI -0·1, -0·06; P<0·001). Among the four hormones, adiponectin was inversely associated with infant growth in both the GDM (ß weight-for-height=-2·49; 95 % CI -3·83, -1·15; P<0·001; ß head-circumference=-0·39; 95 % CI -0·65, -0·13; P=0·003) and healthy groups (ß weight-for-height=-1·42; 95 % CI -2·38, -0·46; P=0·003; ß head-circumference=-0·15; 95 % CI -0·27, -0·03; P=0·007). Maternal BMI and GDM are important determinants of BM hormone concentrations. Milk-borne adiponectin is determined by maternal metabolic status and plays an independent down-regulating role in early infant growth.

High normal blood pressure in early pregnancy also contribute to early onset preeclampsia and severe preeclampsia.

OBJECTIVE: This study was to evaluate effects of high normal blood pressure (HNBP) in early pregnancy on total preeclampsia, early preeclampsia, and severe preeclampsia. METHODS: We conducted a multicenter, national representative retrospective cohort study. HNBP was defined as systolic blood pressure between 130 and 140 mmHg or diastolic blood pressure between 85 and 90 mmHg. We used multivariable logistic regression to examine the associations of HNBP and the risks of above three types of preeclampsia. RESULTS: We included 58 054 women who were normotensive and nulliparous in early pregnancy. 4 809 (8.3%) fulfilled the definition of having HNBP, 16 682 (28.7%) were in normal blood pressure group, and 36 563 (63.0%) were in optimal blood pressure group. The incidence rates of total preeclampsia, early preeclampsia, and severe preeclampsia were 2.1% (1 217), 0.8% (491), and 1.4% (814), respectively. Compared to having optimal blood pressure, women with HNBP had significantly higher odds of total preeclampsia (odds ratio (OR) = 4.028, 95% confidence interval (CI) 3.377, 4.804), severe preeclampsia (OR = 3.542, 95% CI 2.851, 4.400), and early preeclampsia (OR = 8.163, 95% CI 6.219, 10.715). Our restricted cubic spline results supported the dose-response relationship between continuous blood pressure and the odds ratio of three types of preeclampsia. The fraction of early preeclampsia associated with prehypertension was 58.6%, which was higher than those of total preeclampsia (42.2%) or severe preeclampsia (40.5%). CONCLUSION: Women in early pregnancy with HNBP more likely develop total preeclampsia, early preeclampsia and severe preeclampsia, compared to those with optimal blood pressure. HNBP contribute more to early preeclampsia than severe preeclampsia. Our study provided robust epidemiological evidences for monitoring HNBP in early pregnancy to reduce the risks of preeclampsia.

The Dynamic Multisite Interactions between Two Intrinsically Disordered Proteins.

Protein interactions involving intrinsically disordered proteins (IDPs) comprise a variety of binding modes, from the well-characterized folding upon binding to dynamic fuzzy complexes. To date, most studies concern the binding of an IDP to a structured protein, while the interaction between two IDPs is poorly understood. In this study, NMR, smFRET, and molecular dynamics (MD) simulation are combined to characterize the interaction between two IDPs, the C-terminal domain (CTD) of protein 4.1G and the nuclear mitotic apparatus (NuMA) protein. It is revealed that CTD and NuMA form a fuzzy complex with remaining structural disorder. Multiple binding sites on both proteins were identified by molecular dynamics and mutagenesis studies. This study provides an atomic scenario in which two IDPs bearing multiple binding sites interact with each other in dynamic equilibrium. The combined approach employed here could be widely applicable for investigating IDPs and their dynamic interactions.

Conformational Dynamics of apo-GlnBP Revealed by Experimental and Computational Analysis.

The glutamine binding protein (GlnBP) binds l-glutamine and cooperates with its cognate transporters during glutamine uptake. Crystal structure analysis has revealed an open and a closed conformation for apo- and holo-GlnBP, respectively. However, the detailed conformational dynamics have remained unclear. Herein, we combined NMR spectroscopy, MD simulations, and single-molecule FRET techniques to decipher the conformational dynamics of apo-GlnBP. The NMR residual dipolar couplings of apo-GlnBP were in good agreement with a MD-derived structure ensemble consisting of four metastable states. The open and closed conformations are the two major states. This four-state model was further validated by smFRET experiments and suggests the conformational selection mechanism in ligand recognition of GlnBP.

Biphenyl tetracarboxylic acid-based metal-organic frameworks: a case of topology-dependent thermal expansion.

The large inherent flexibility and highly modular nature of metal-organic frameworks (MOFs) make them ideal candidates for the study of negative thermal expansion (NTE). Among diverse organic ligands, the biphenyl unit, which can unrestrictedly rotate along its C-C single bond, can largely enhance the structural flexibility. Herein, we explored the thermal expansion behaviors of four indium biphenyl tetracarboxylates (BPTCs). Owing to the different dihedral angles of BPTC ligands and coordination mode of In3+, they show distinct topologies: InOF-1 (nti), InOF-2 (unc), InOF-12 (pts) and InOF-13 (nou). Intriguingly, it is found that the thermal expansion is highly dependent on the specific topology. The MOFs featuring mononuclear nodes show normal positive thermal expansion (PTE), and the magnitudes of coefficients follow the trend of InOF-2 < InOF-12 < InOF-13, inversely related to averaged molecular volumes. In contrast, the InOF-1, composed of a 1D chain of corner-shared InO6 octahedrons, shows pronounced NTE. Detailed high-resolution synchrotron powder X-ray diffraction and lattice dynamic analyses shed light on the fact that NTE in the InOF-1 is a synergy effect of the spring-like distortion of the inorganic 1D helical chain and twisting of the BPTC ligands. The present work shows how the topological arrangement of building blocks governs the thermal expansion behaviors.

Therapeutic Efficacy and Safety of Intense Pulsed Light for Meibomian Gland Dysfunction in Patients with Chronic Ocular Graft-Versus-Host Disease.

PURPOSE: To evaluate the efficacy and safety of intense pulsed light combined with meibomian gland expression (IPL-MGX) for treating meibomian gland dysfunction (MGD) associated with chronic ocular graft-versus-host disease (oGVHD). METHODS: This retrospective study included 18 patients (18 eyes) with Fitzpatrick skin type ≤ IV, who underwent 3 to 8 sessions of IPL-MGX. Dry eye symptomology, ocular surface parameters, and adverse events were evaluated. RESULTS: Of 18 eyes, 83.3% and 66.7% showed severe oGVHD and severe MGD, respectively. At 4 weeks after the final session, significant improvements in the OSDI (P < 0.001), SPEED (P = 0.001), meibum expressibility (P < 0.001), and meibum quality (P = 0.016) were observed. At 12 weeks after, the OSDI (P = 0.009), SPEED (P = 0.002), and meibum expressibility (P = 0.008) significantly improved. No adverse events owing to IPL were reported. CONCLUSION: IPL-MGX may improve the ocular symptoms, ameliorate meibomian gland secretion, and is considered as a safe treatment for MGD in oGVHD patients.

Posterior segment complications and the risk factors after allogeneic hematopoietic stem cell transplantation.

PURPOSE: To study the posterior segment complications (PSC) and the risk factors in patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This cross-sectional, case-control study enroled 143 patients who received allogeneic HSCT. Comprehensive ocular examinations were performed to evaluate PSC and ocular Graft-versus-Host Disease (oGVHD). PSC was diagnosed based on the characteristic fundus findings and auxiliary examinations. Visual-evoked potential was examined in patients with unexplained visual loss and suspected visual pathway pathology (VPP). Ocular surface disease index, corneal fluorescein staining, conjunctival injection and Schirmer's test were scored to diagnose oGVHD. RESULTS: PSC was detected in 36 (25.2%) patients, while 107 (74.8%) patients were not. Among them, 102 (71.3%) patients were diagnosed with oGVHD. The most common PSC included cytomegalovirus retinitis (13/143, 9.1%) and VPP (7/143, 4.9%). Central nervous system relapse of leukaemia was detected in four out of seven cases of VPP. Patients with PSC had worse visual acuity, lower prevalence and milder severity of oGVHD, and more donors from unrelated and human leucocyte antigen (HLA)-mismatch (all P < 0.05). PSC was associated with transplant from unrelated (OR = 6.494, 95% CI: 1.635-25.794, P = 0.008) and HLA-mismatched (OR = 7.193, 95% CI: 2.829-18.291, P < 0.001) donor but not with the occurrence of systemic GVHD or oGVHD. CONCLUSIONS: PSC in post-HSCT patients was more common than previously noted, deserving the concern of ophthalmologists, especially in patients with unrelated or HLA-mismatched donors.

Integrated metabolomics and lipidomics analyses suggest the temperature-dependent lipid desaturation promotes aflatoxin biosynthesis in Aspergillus flavus.

Temperature is one of the main factors affecting aflatoxin (AF) biosynthesis in Aspergillus flavus. Previous studies showed that AF biosynthesis is elevated in A. flavus at temperatures between 28°C-30°C, while it is inhibited at temperatures above 30°C. However, little is known about the metabolic mechanism underlying temperature-regulated AF biosynthesis. In this study, we integrated metabolomic and lipidomic analyses to investigate the endogenous metabolism of A. flavus across 6 days of mycelia growth at 28°C (optimal AF production) and 37°C (no AF production). Results showed that both metabolite and lipid profiles were significantly altered at different temperatures. In particular, metabolites involved in carbohydrate and amino acid metabolism were up-regulated at 37°C on the second day but down-regulated from days three to six. Moreover, lipidomics and targeted fatty acids analyses of mycelia samples revealed a distinct pattern of lipid species and free fatty acids desaturation. High degrees of polyunsaturation of most lipid species at 28°C were positively correlated with AF production. These results provide new insights into the underlying metabolic changes in A. flavus under temperature stress.

p53 and Sp1 cooperate to regulate the expression of Epstein-Barr viral Zta protein.

Epstein-Barr virus (EBV) belongs to the gammaherpesvirus family. To produce infectious progeny, EBV reactivates from latency into the lytic cycle by expressing the determinative lytic transactivator, Zta. In the presence of histone deacetylase inhibitor (HDACi), p53 is a prerequisite for the initiation of the EBV lytic cycle by facilitating the expression of Zta. In this study, a serial mutational analysis of Zta promoter (Zp) indicated an important role for the ZID element in responding to HDACi induction and p53 binds to this ZID element together with Sp1, a universal transcription factor. Abolition of the DNA-binding ability of Sp1 reduces the inducibility of ZID by HDACi and also reduces the amount of p53 binding to ZID. Finally, it was shown that EBV in p53-positive-lymphoblastoid cell lines (LCLs) can enter into the lytic cycle spontaneously; however, knockdown of p53 in LCLs leads to retardation of EBV reactivation.

Methionine addition improves the acid tolerance of Lactiplantibacillus plantarum by altering cellular metabolic flux, energy distribution, lipids composition.

This paper reported a wine-derived lactic acid bacterium, Lactiplantibacillus plantarum XJ25, which exhibited higher cell viability under acid stress upon methionine supplementation. Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation. Transcriptional analysis showed L. plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress. Subsequent overexpression assays proved that methionine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress. Finally, L. plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids (SFAs) in membrane. These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.