Adherence to the low-fat diet pattern reduces the risk of lung cancer in American adults aged 55 years and above: a prospective cohort study.

OBJECTIVES: There is little evidence on the association between low-fat dietary patterns and lung cancer risk among middle-aged and older adults. To fill this gap, we comprehensively investigated the association of adherence to a low-fat diet (LFD) and intake of different fat components including saturated, monounsaturated, and polyunsaturated fatty acids with incidence of lung cancer and its subtypes [non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)] among adults aged 55 years and older. DESIGN: A prospective cohort study with a mean follow-up time of 8.8 years. SETTING AND PARTICIPANTS: This study used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. The study population included 98,459 PLCO participants age 55 and over at baseline who completed food frequency questionnaires providing detailed dietary information and had no history of cancer. METHODS: Dietary intake was assessed using a validated food frequency questionnaire at baseline. A LFD score was calculated based on fat, protein, and carbohydrate intake as a percentage of total calories. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between LFD score and intake of fat components (in quartiles) and incident lung cancer and its subtypes over follow-up. Restricted cubic spline analyses were conducted to examine possible nonlinear relationships. Subgroup analyses were performed to evaluate potential effect modifiers, and several sensitivity analyses were conducted to assess the stability of the findings. RESULTS: During a follow-up of 869,807.9 person-years, 1,642 cases of lung cancer were observed, consisting of 1,408 (85.75%) cases of NSCLC and 234 (14.25%) cases of SCLC. The highest versus the lowest quartiles of the LFD score were found to be associated with a reduced risk of lung cancer (HR, 0.76; 95% CI, 0.66-0.89), NSCLC (HR, 0.79; 95% CI, 0.67-0.93), and SCLC (HR, 0.59; 95% CI, 0.38-0.92). The restricted cubic spline plots demonstrated a linear dose-response relationship between the LFD score and the risk of lung cancer as well as its subtypes. This risk reduction association for overall lung cancer was more pronounced in smokers (HR, 0.71; 95% CI, 0.60-0.84; P for interaction = 0.003). For fat components, high consumption of saturated fatty acids was associated with an increased lung cancer risk (HR, 1.35; 95% CI, 1.10-1.66), especially for SCLC (HR, 2.05; 95% CI, 1.20-3.53). No significant association was found between consumption of monounsaturated or polyunsaturated fatty acids and incident lung cancer and its subtypes. CONCLUSIONS: Our findings suggest that adherence to LFD may reduce the lung cancer risk, particularly in smokers; while high saturated fatty acids consumption may increase lung cancer risk, especially for SCLC, among middle-aged and older adults in the US population.

Genomic characterisation of blaNDM-5-IncX3 plasmid in an ST4 Klebsiella aerogenes clinical isolate.

OBJECTIVES: The dissemination of New Delhi metallo-ß-lactamase-5 (NDM-5) among various species of Enterobacterales has attracted serious global attention. Here, we characterise the genomic characterisation of blaNDM-5-IncX3 plasmid (pNDM-KA3) in an ST4 Klebsiella aerogenes (KA3) strain isolated from a neonate with pneumonia. METHODS: Antimicrobial susceptibility and multilocus sequence typing was performed for the KA3. The plasmid conjugation assay and plasmid stability of the KA3 (pNDM-KA3) were also analysed. The pNDM-KA3 plasmid was further analysed by whole-genome sequencing and comparative analysis to determine the genetic environment of blaNDM-5. RESULTS: The KA3 strain belongs to ST4 and shows high resistance to ß-lactam antibiotics, including carbapenems, but is susceptible to ciprofloxacin, amikacin, tigecycline, and colistin. The pNDM-KA3 was successfully transferred to the recipient E. coli J53 and showed strong stability in K. aerogenes. Genomic sequencing revealed that the pNDM-KA3 plasmid was assigned to plasmid incompatibility group X3 with 43367 bp, and a conserved structure sequence of △IS3000-△ISAba125-IS5-blaNDM-5-bleMBL- trpF-dsbC-IS26 was detected upstream and downstream of the blaNDM-5 gene. Further analysis revealed that insertion sequences mediated the dissemination of blaNDM-5 from other species of Enterobacterales. The pNDM-KA3 showed high similarity to blaNDM-5-harbouring plasmids in other species of Enterobacterales, with these plasmids carrying genes for replication (repB), partitioning (parA and parB), stability (hns), and conjugative transfer (virB and virD). CONCLUSIONS: Continued monitoring for the dissemination of blaNDM-5 among uncommon Enterobacterales species should be further reinforced.

Altered intestinal microbiota enhances adenoid hypertrophy by disrupting the immune balance.

Introduction: Adenoid hypertrophy (AH) is a common upper respiratory disorder in children. Disturbances of gut microbiota have been implicated in AH. However, the interplay of alteration of gut microbiome and enlarged adenoids remains elusive. Methods: 119 AH children and 100 healthy controls were recruited, and microbiome profiling of fecal samples in participants was performed using 16S rRNA gene sequencing. Fecal microbiome transplantation (FMT) was conducted to verify the effects of gut microbiota on immune response in mice. Results: In AH individuals, only a slight decrease of diversity in bacterial community was found, while significant changes of microbial composition were observed between these two groups. Compared with HCs, decreased abundances of Akkermansia, Oscillospiraceae and Eubacterium coprostanoligenes genera and increased abundances of Bacteroides, Faecalibacterium, Ruminococcus gnavus genera were revealed in AH patients. The abundance of Bacteroides remained stable with age in AH children. Notably, a microbial marker panel of 8 OTUs were identified, which discriminated AH from HC individuals with an area under the curve (AUC) of 0.9851 in the discovery set, and verified in the geographically different validation set, achieving an AUC of 0.9782. Furthermore, transfer of mice with fecal microbiota from AH patients dramatically reduced the proportion of Treg subsets within peripheral blood and nasal-associated lymphoid tissue (NALT) and promoted the expansion of Th2 cells in NALT. Conclusion: These findings highlight the effect of the altered gut microbiota in the AH pathogenesis.

Pathogenicity and Interspecies Transmission of Cluster 3 Tembusu Virus Strain TMUV HQ-22 Isolated from Geese.

Since 2010, the Tembusu virus (TMUV) has been highly prevalent in China, causing significant economic losses to the poultry industry. In 2022, a suspected outbreak of TMUV occurred at a goose farm located in Anhui Province. A strain of TMUV, TMUV HQ-22, was isolated from the infected geese. Phylogenetic analysis using the E gene of the HQ-22 strain demonstrated its affiliation with cluster 3, a less commonly reported cluster in comparison to the main circulating cluster, cluster 2. Through a comparison of the envelope (E) protein of HQ-22 with other typical TMUV strains, a mutation at the 157th amino acid position was identified, wherein valine (V) in cluster 3 changed to alanine (A), a characteristic that is unique to cluster 2. These findings highlight the diversity and complexity of the TMUV strains circulating in China. In our experimental analysis, an injection of TMUV HQ-22 into the muscles of 3-day-old goslings resulted in severe neurological symptoms and a mortality rate of 60%. Similarly, the intracranial or intranasal infection of 3-week-old ICR mice with TMUV HQ-22 led to severe neurological symptoms and respective mortality rates of 100% or 10%. In summary, our study isolated a TMUV strain, TMUV HQ-22, from geese that belongs to cluster 3 and exhibits significant pathogenicity in both goslings and ICR mice. These results emphasize the genetic diversity of the TMUV circulating in China and expand the host range beyond mosquitoes to include ducks, chickens, geese, and even mice. It is crucial to not underestimate the risk of TMUV infection in mammals, warranting our utmost attention.

Recent Advances in Bacterial Persistence Mechanisms.

The recurrence of bacterial infectious diseases is closely associated with bacterial persisters. This subpopulation of bacteria can escape antibiotic treatment by entering a metabolic status of low activity through various mechanisms, for example, biofilm, toxin-antitoxin modules, the stringent response, and the SOS response. Correspondingly, multiple new treatments are being developed. However, due to their spontaneous low abundance in populations and the lack of research on in vivo interactions between persisters and the host's immune system, microfluidics, high-throughput sequencing, and microscopy techniques are combined innovatively to explore the mechanisms of persister formation and maintenance at the single-cell level. Here, we outline the main mechanisms of persister formation, and describe the cutting-edge technology for further research. Despite the significant progress regarding study techniques, some challenges remain to be tackled.

Identification Strategy of Biological Half Sibling Relationship.

OBJECTIVES: To compare the application value of the likelihood ratio (LR) method and identity by state (IBS) method in the identification involving half sibling relationships, and to provide a reference for the setting of relevant standards for identification of half sibling relationship. METHODS: (1) Based on the same genetic marker combinations, the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score (CIBS) and combined full sibling index in actual cases with the distributions in simulated cases. (2) In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters, were calculated. (3) The application value of LR method was compared with that of IBS method, by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. (4) According to the existing simulation data, the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. RESULTS: (1) After the rank sum test, under the premise that the real relationship and the genetic marker combination tested were the same, there was no significant difference between the simulation method and the results obtained in the actual case. (2) In most cases, under the same conditions, the system effectiveness obtained by LR method was greater than that by IBS method. (3) According to the existing data, the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. CONCLUSIONS: When distinguishing half sibling from full sibling pairs or unrelated pairs, it is recommended to give preference to the LR method, and estimate the required number of markers according to the identification types and the population data, to ensure the identification effect.

Silibinin alleviates ferroptosis of rat islet ß cell INS-1 induced by the treatment with palmitic acid and high glucose through enhancing PINK1/parkin-mediated mitophagy.

Type 2 diabetes (T2DM) is induced by the abundance of glucose and lipids, which causes glucolipotoxicity to the pancreatic ß-cells. Silibinin is a natural flavonoid possessing the regulatory activity on insulin production and therapeutic activity in diabetic mice; however, its effect on glucolipotoxicity is not fully explained. This in vitro study investigates the effects of silibinin on palmitic acid (PA) and high glucose (HG)-induced cell loss and ferroptosis of rat insulinoma INS-1 cells. In the cells treated with PA and HG, expressions of glucose transporter 4 (Glut4) and carnitine acyltransferase I (CPT1) for ß-oxidation of fatty acids are reduced. Mitochondria are the metabolic organelles for glucose and fatty acids. The mitochondrial membrane potential (MMP) and ATP production were decreased, while the ROS level was elevated in the cells treated with PA and HG, indicating an induction of mitochondrial disorder. Cell loss was partially rescued by ferroptosis inhibition, suggesting an involvement of ferroptosis in the cells treated with PA and HG. More importantly, the increases in total iron, lipid ROS, MDA and COX-2, and the decrease in ferroptosis inhibitory molecules GSH, GPX4 and FSP1 appeared in the cells treated with PA and HG, confirming the occurrence of ferroptosis. Moreover, PINK1/parkin-mediated mitophagy, a vital process for selective elimination of damaged mitochondria, was blocked. Interestingly, silibinin rescued the mitochondria, restricted the ferroptosis and restored the mitophagy. By using the pharmacological stimulator and inhibitor of mitophagy, and si-RNA transfection to silence PINK1 expression, silibinin's protective effect against ferroptosis caused by PA and HG treatment was found to depend on mitophagy. Collectively, our current study reveals the new mechanisms for the protection of silibinin against the injury of INS-1 cells treated with PA and HG, elucidates the participation of ferroptosis in glucolipotoxicity, highlighting the involvement of mitophagy in defense against ferroptotic cell death.

Genotype-phenotype pattern analysis of pathogenic PAX9 variants in Chinese Han families with non-syndromic oligodontia.

Background: Non-syndromic oligodontia is characterized by the absence of six or more permanent teeth, excluding third molars, and can have aesthetic, masticatory, and psychological consequences. Previous studies have shown that PAX9 is associated with autosomal dominant forms of oligodontia but the precise molecular mechanisms are still unknown. Methods: Whole-exome and Sanger sequencing were performed on a cohort of approximately 28 probands with NSO, for mutation analysis. Bioinformatic analysis was performed on the potential variants. Immunofluorescence assay, western blotting, and qPCR were used to explore the preliminary functional impact of the variant PAX9 proteins. We reviewed PAX9-related NSO articles in PubMed to analyze the genotype-phenotype correlations. Results: We identified three novel PAX9 variants in Chinese Han families: c.152G>T (p.Gly51Val), c.239delC (p.Thr82Profs*3), and c.409C>T (q.Gln137Ter). In addition, two previously reported missense variants were identified: c.140G>C (p.Arg47Pro) and c.146C>T (p.Ser49Leu) (reference sequence NM_006194.4). Structural modeling revealed that all missense variants were located in the highly conserved paired domain. The other variants led to premature termination of the protein, causing structural impairment of the PAX9 protein. Immunofluorescence assay showed abnormal subcellular localizations of the missense variants (R47P, S49L, and G51V). In human dental pulp stem cells, western blotting and qPCR showed decreased expression of PAX9 variants (c.140G>C, p.R47P, and c.152G>T, p.G51V) compared with the wild-type group at both the transcription and translation levels. A review of published papers identified 64 PAX9 variants related to NSO and found that the most dominant feature was the high incidence of missing upper second molars, first molars, second premolars, and lower second molars. Conclusion: Three novel PAX9 variants were identified in Chinese Han families with NSO. These results extend the variant spectrum of PAX9 and provide a foundation for genetic diagnosis and counseling.

Development and evaluation of a novel panel containing 188 microhaplotypes for 2nd-degree kinship testing in the Hebei Han population.

Distant kinship identification is one of the critical problems in forensic genetics. As a new type of genetic marker defined and discussed in the last decade, the microhaplotype (MH) has drawn much attention in such identification owing to its specific advantages to traditional short tandem repeat (STR) or single nucleotide polymorphism (SNP) markers. In this study, MH markers were screened step by step from the 1000 Genomes Project database, and a novel multiplex panel containing 188 MHs (in which 181 are reported the first time, while 1 was reported in a previous study and the other 6 have partial overlaps with known markers) was constructed for application in 2nd- and 3rd-degree kinship identification. Along with the construction, a novel MH nomenclature was proposed, in which the SNP position information they contained was taken into account to eliminate the possibility that the same locus was named differently interlaboratory. After a series of evaluations, the panel was shown to have good sequencing accuracy, high sensitivity, species specificity, and resistance to anti-PCR inhibitors or degradation. Population data of the 188 MHs were calculated based on the genetic information of 221 unrelated Hebei Han individuals, and the effective number of alleles (Ae) ranged from 2.0925 to 8.2634 (with an average of 2.9267). For the whole system, the cumulative matching probability (CMP), the cumulative power of exclusion in paternity testing of duos (CPEduo) and that of trios (CPEtrio) reached 2.8422 × 10-137, 1-1.3109 × 10-21, and 1-2.8975 × 10-39, respectively, indicating that this panel was satisfactory for individual identification and paternity testing. Then, the efficiency of the 188 MHs in 2nd- and 3rd-degree kinship testing was studied based on 30 extended families consisting of 179 2nd-degree and 121 3rd-degree relatives, as well as simulations of 0.5 million pairs of those two kinships. The results showed that clear opinions would be given in 83.36% of 2nd-degree identifications with a false rate less than 10-5, when the confirming and excluding thresholds of cumulative likelihood ratio (CLR) were set as 104 and 10-4, respectively. This panel is still not sufficient to solve the problem of 3rd-degree kinship identification alone, and approximately 300 or 870 MH loci would be needed in 2nd- or 3rd-degree kinship identification, respectively, to achieve a system efficiency not less than 0.99 with such a threshold set; such necessary numbers would be used only as a reference in further research.

Association between Intestinal Colonization and Extraintestinal Infection with Carbapenem-Resistant Klebsiella pneumoniae in Children.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a critical public health threat. However, the association between intestinal colonization and parenteral infection among pediatric patients has not been elucidated. We collected 8 fecal CRKP strains and 10 corresponding CRKP strains responsible for extraintestinal infection from eight patients who did not manifest infection upon admission to the hospital. Paired isolates showed identical resistance to antimicrobials and identical virulence in vitro and in vivo. wzi capsule typing, multilocus sequence typing, and whole-genome sequencing (WGS) indicated high similarity between paired colonizing and infecting isolates. Mutations between colonizing and infecting isolate pairs found by WGS had a distinctive molecular signature of a high proportion of complex structural variants. The mutated genes were involved in pathways associated with infection-related physiological and pathogenic functions, including antibiotic resistance, virulence, and response to the extracellular environment. The latter is important for bacterial infection of environmental niches. Various mutations related to antibiotic resistance, virulence, and colonization that were not associated with any particular mutational hot spot correlated with an increased risk of extraintestinal infection. Notably, novel subclone carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) KL19-ST15 exhibited hypervirulence in experimental assays that reflected the severe clinical symptoms of two patients infected with the clonal strains. Taken together, our findings indicate the association between CRKP intestinal colonization and extraintestinal infection, suggesting that active screening for colonization on admission could decrease infection risk in children. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) causes an increasing number of nosocomial infections, which can be life-threatening, as carbapenems are last-resort antibiotics. K. pneumoniae is part of the healthy human microbiome, and this provides a potential advantage for infection. This study demonstrated that CRKP intestinal colonization is strongly linked to extraintestinal infection, based on the evidence given by whole-genome sequencing data and phenotypic assays of antimicrobial resistance and virulence. Apart from these findings, our in-depth analysis of point mutations and chromosome structural variants in patient-specific infecting isolates compared with colonizing isolates may contribute insights into bacterial adaptation underlying CRKP infection. In addition, a novel subclone of carbapenem-resistant hypervirulent K. pneumoniae (CR-hvKP) was observed in the study. This finding highlights the importance of CRKP active surveillance among children, targeting in particular the novel high-risk CR-hvKP clone.

Unbiased molecular dynamics simulation of a first-in-class small molecule inhibitor binds to oncostatin M.

Small molecule inhibitors (SMIs) targeting oncostatin M (OSM) signaling pathway represent new therapeutics to combat cancer, inflammatory bowel disease (IBD) and CNS disease. Recently, the first-in-class SMI named SMI-10B that target OSM and block its interaction with receptor (OSMR) were reported. However, the binding pocket and interaction mode of the compound on OSM remain poorly understood, which hampering the rational design of SMIs that target OSM. Here, using SMI-10B as a probe, the multiple pockets on OSM for small molecules binding were extensively explored by unbiased molecular dynamics (MD) simulations. Then, the near-native structure of the complex was identified by molecular mechanics generalized Born surface area (MM/GBSA) binding energy funnel. Moreover, the binding stabilities of the protein-ligand complexes in near- and non-native conformations were verified by additional independent MD runs and absolute free energy perturbation (FEP) calculation. In summary, the unique feature of SMI-10B spontaneously binds to OSM characterized here not only provide detailed information for understanding the molecular mechanism of SMI-10B binding to OSM, but also will facilitate the rational design of novel and more potent SMIs to block OSM signaling.

The gut microbiome and obstructive sleep apnea syndrome in children.

Obstructive sleep apnea syndrome (OSAS) in children has become a major public health problem that affects the physical and mental growth of children. OSAS can result in adverse outcomes during growth and development, inhibiting the normal development of the metabolic, cardiovascular, and immune systems. OSAS is characterized by partial or complete obstruction of the upper airway, and prolonged obstruction that causes intermittent hypoxia and sleep fragmentation in children. The human microbiota is a complex community that is in dynamic equilibrium in the human body. Intermittent hypoxia and sleep fragmentation induced by childhood OSAS alter the composition of the gut microbiome. At the same time, changes in the gut microbiome affect sleep patterns in children through immunomodulatory and metabolic mechanisms, and induce further comorbidities, such as obesity, hypertension, and cardiovascular disease. This article discusses recent progress in research into the mechanisms of OSAS-induced changes in the gut microbiota and its pathophysiology in children.

Nosocomial dissemination of hypervirulent Klebsiella pneumoniae with high-risk clones among children in Shanghai.

Objectives: Although hypervirulent Klebsiella pneumoniae (hvKp) is an increasing public health problem, there remains limited epidemiological information regarding hvKp infections in children. Here, we conducted a clinical, molecular and phenotypic surveillance of hvKp strains in a pediatric population. Methods: Non-repetitive K. pneumoniae (Kp) strains consecutively collected during 2019-2020 were screened for hypervirulence genes (prmpA, prmpA2, iucA, iroB, and peg344) using PCR. Positive strains were further characterized by four phenotypic assays (string test, serum killing assay, siderophore production, Galleria mellonella lethality assay), followed by murine sepsis model to determine virulence in vitro and in vivo. Also, capsular types, sequence types, plasmid replicon types, antimicrobial resistance determinants and susceptibility were analyzed. Results: A total of 352 isolates were collected, wherein 83 (23.6%) were hypervirulence genes-positive Kp (hgKp). A significant increase in KPC-2-producing KL47-ST11 among hgKp strains was observed, from 5.3% (1/19) in 2019 to 67.6% (25/37) in 2020 (P<.0001), suggesting the potential dissemination of the hybrid virulence and carbapenem-resistance encoding plasmid among children. Further, hgKp isolates were classified into hvKp (n = 27) and hgKp-low virulence (hgKp-Lv) (n = 56) based on virulence phenotypic assays. In hvKp, diverse genetic clones were observed and K1-ST23 or K2-ST25 strains with sensitivity to multiple antibiotics were prevalent (25.9%, 7/27). Compared with hgKp-Lv, hvKp infection had a higher propensity to involve severe pneumonia (22.2% vs. 12.5%) in elder children and significant higher mortality in mice (P = 0.0086). Additionally, either hvKp or hgKp-Lv infections were mostly healthcare-associated and hospital-acquired (74.1% vs. 91.9%). Conclusions: These data suggest that K1-ST23 and K2-ST25 are high-risk clones of hvKp, and the genetic convergence of virulence and carbapenem-resistance is increasing among children. Control measures are needed to prevent the dissemination in clinical settings.

Interactions between anthropogenic pollutants (biodegradable organic nitrogen and ammonia) and the primary hydrogeochemical component Mn in groundwater: Evidence from three polluted sites.

Anthropogenic pollutants (organic nitrogen and ammonia) can change the dynamic balances of hydrogeochemical components of groundwater, and this can affect the fates of the pollutants and groundwater quality. The aim of this paper is to assess the long-term impact of pollutants on groundwater component concentrations and species in three sites that has been polluted with illegal discharge wastewater containing organic nitrogen and ammonia, in order to reveal the interactions between nitrogen species and Mn. We analyzed semi-monthly groundwater data from three sites in northwestern China over a long period of time (2015-2020) by using statistical analyses, correlation analyses, and a correlation co-occurrence network method. The results showed that wastewater entering groundwater from surface changed the hydrogeochemical component concentrations and species significantly. The main form of inorganic nitrogen species changed from nitrate to ammonia. The Mn concentration increased from undetectable (<0.01 mg/L) to 1.64 mg/L (the maximum), which surpassed the guideline value suggested by China and WHO. The main mechanism for Mn increase is the reductive dissolution of Mn oxide caused by the oxidation of organic nitrogen. Mn­nitrogen species interaction complicates the transformation of nitrogen components. Chemoautotrophic denitrification and dissimilatory nitrate reduction to ammonium (DNRA) mediated by Mn are the major mechanisms of nitrate attenuation when dissolved oxygen is greater than 2 mg/L. Mn oxides reductive dissolution and reoxidation of Mn by nitrate reduction cause Mn to circulate in groundwater. The results provide field evidence for interactions between nitrogen species transformation and Mn cycle in groundwater. This has important implications for pollution management and groundwater remediation, particularly monitored natural attenuation.

A novel EDAR missense mutation identified by whole-exome sequencing with non-syndromic tooth agenesis in a Chinese family.

BACKGROUND: Causative variants in genes of the EDA/EDAR/NF-κB pathway, such as EDA and EDARADD, have been widely identified in patients with non-syndromic tooth agenesis (NSTA). However, few cases of NSTA are due to ectodysplasin-A receptor (EDAR) variants. In this study, we investigated NSTA-associated variants in Chinese families. METHODS: Peripheral blood samples were collected from the family members of 24 individuals with NSTA for DNA extraction. The coding region of the EDA gene of the 24 probands was amplified by PCR and sequenced to investigate new variants. Whole-exome sequencing and Sanger sequencing were then performed for probands without EDA variants detected by PCR. RESULTS: A novel missense variant EDAR c.338G>A (p.(Cys113Tyr)) was identified in one family. In addition, three known EDA variants (c.865C>T, c.866G>A, and c.1013C>T) were identified in three families. Genotype-phenotype correlation analysis of EDAR gene mutation showed that NSTA patients were most likely to lose the maxillary lateral incisors and the maxillary central incisors were the least affected. The phenotype of mutations at codon 289 of EDA in NSTA affected patients was characterized by lateral incisors loss, rarely affecting the maxillary first molars. CONCLUSION: A novel EDAR missense variant c.338G>A (p.(Cys113Tyr)) was identified in a family with NSTA, extending the mutation spectrum of the EDAR gene. Genotype-phenotype correlation analyses of EDAR and EDA mutations could help to improve disease status prediction in NSTA families.

Cross-reactivity of two human IL-6 family cytokines OSM and LIF explored by protein-protein docking and molecular dynamics simulation.

BACKGROUND: Oncostatin M (OSM) and leukemia inhibitory factor (LIF) are two important pro-inflammatory cytokines of the interleukin-6 (IL-6) family. The two cytokines mediated signaling was recently found to be closely associated with cancer and chronic inflammation, which represent promising therapeutic targets for the treatment of many solid tumors and inflammatory disease. As the most closely related members, cross-reactivity of them may result in undesired activation of off-target cells, leading to toxicity or lack of efficacy of the therapeutic effects. However, the mechanism of the cross-reactivity of OSM and LIF is not well understood. METHODS: In this work, protein-protein docking, molecular dynamics (MD) simulations with explicit solvent and post endpoints binding free energy (BFE) analysis were carried out to further understand the structural and energetic principles of interactions between the two cytokines and the shared receptor LIFR. RESULTS: For the first time, the simulation given a computational model of OSM-LIFR interaction, and provided significant insights into the mechanism of OSM and LIF cross-react with LIFR. The identified common features shared by OSM and LIF bind to LIFR involving 10 "conserved" residues (90% similarity) distributed at the binding site III comprised of AB loop, BC loop and D helix. In addition, 11 shared residues were identified in LIFR contribute 77.85% and 84.63% energies for OSM and LIF binding, which play a critical role in the formation of the two cytokine-receptor complexes. Moreover, the "nonconserved" residues at the same position of cytokines such as Asp41 in OSM and Pro51 in LIF as well as the three residues (Glu338, Asn201 and Glu260) in LIFR were also discovered. CONCLUSIONS: These important information may facilitate the rational design of novel chemical or biological agents with less toxicity and improved efficacy.

Rapid biosynthesis of fluorescent CdSe QDs in Bacillus licheniformis and correlative bacterial antibiotic change assess during the process.

Cadmium selenide (CdSe) quantum dots (QDs) were biosynthesized rapidly in 18 h in Bacillus licheniformis ATCC 11946 (B. licheniformis); this process benefited from the cellular machinery of bacteria metal metabolism, in which inorganic Na2 SeO3 and CdCl2 were chosen as raw materials to produce high quality CdSe QDs by a designed two-step protocol. Research outcomes demonstrated that the purified CdSe QDs possessed maximum fluorescence intensities at weak alkalinity solutions and had good fluorescence stabilities at 4°C as well as at room temperature after standing for 1 week. Glutathione (GSH) concentration and superoxide dismutase (SOD) content, both of which were reported to be greatly related to biosynthetic activities in some bacterial matrices, were monitored during the biosynthetic process in B. licheniformis. Bacterial resistance research further showed that the change in rates in bacterial inhibition zone diameter to seven different antibiotics was less than 9% after B. licheniformis was used to manufacture CdSe QDs, showing a relative lower environmental risk in short-term heavy metal exposure.

Quality change mechanism and drinking safety of repeatedly-boiled water and prolonged-boil water: a comparative study.

Quality, safety and potability of repeatedly-boiled water (RBW) and prolonged-boil water (PBW) lead to concern and even misgivings in the public from time to time, especially in China, and other societies have a habit of drinking boiled water, with improvements of living standards and owing to increasing concerns for human health. This phenomenon is mainly attributed to the fact that the conclusions drawn from existing scientific experiments could not respond well to the concerns. In order to make up for this deficiency, tap water was selected to carry out RBW and PBW experiments independently. The quality changes of RBW and PBW show very similar trends that are not as great as might be imagined, and both are impacted by the tap water quality and the physiochemical effects. The dominating physiochemical effects are the water evaporation and the resulting concentration of unreactive components (most dissolved components), which can be easily explained by the existing evaporation-concentration theory. The results show that tap water will be still safe and potable after being frequently boiled or after having undergone prolonged boiling, as long as it satisfies the sanitary standards of drinking water prior to heating. Therefore, there is no need to worry about drinking RBW or PBW in daily life.

A high activity zinc transporter OsZIP9 mediates zinc uptake in rice.

Zinc (Zn) is an essential micronutrient for most organisms including humans, and Zn deficiency is widespread in human populations, particularly in underdeveloped regions. Cereals such as rice (Oryza sativa) are the major dietary source of Zn for most people. However, the molecular mechanism underlying Zn uptake in rice is still not fully understood. Here, we report that a member of the ZIP (ZRT, IRT-like protein) family, OsZIP9, contributes to Zn uptake in rice. It was expressed in the epidermal and exodermal cells of lateral roots, localized in the plasma membrane and induced during Zn deficiency. Yeast-expressed OsZIP9 showed much higher Zn influx transport activity than other rice ZIP proteins in a wide range of Zn concentrations. OsZIP9 knockout rice plants showed a significant reduction in growth at low Zn concentrations, but could be rescued by a high Zn supply. Compared with the wild type, accumulation of Zn in root, shoot and grain was much lower in knockout lines, particularly with a low supply of Zn under both hydroponic and paddy soil conditions. OsZIP9 also showed Co uptake activity. Natural variation of OsZIP9 expression level is highly associated with Zn content in milled grain among rice varieties in the germplasm collection. Taken together, these results show that OsZIP9 is an important influx transporter responsible for the take up of Zn and Co from external media into root cells.