Landscape of RNA pseudouridylation in archaeon Sulfolobus islandicus.

Pseudouridine, one of the most abundant RNA modifications, is synthesized by stand-alone or RNA-guided pseudouridine synthases. Here, we comprehensively mapped pseudouridines in rRNAs, tRNAs and small RNAs in the archaeon Sulfolobus islandicus and identified Cbf5-associated H/ACA RNAs. Through genetic deletion and in vitro modification assays, we determined the responsible enzymes for these modifications. The pseudouridylation machinery in S. islandicus consists of the stand-alone enzymes aPus7 and aPus10, and six H/ACA RNA-guided enzymes that account for all identified pseudouridines. These H/ACA RNAs guide the modification of all eleven sites in rRNAs, two sites in tRNAs, and two sites in CRISPR RNAs. One H/ACA RNA shows exceptional versatility by targeting eight different sites. aPus7 and aPus10 are responsible for modifying positions 13, 54 and 55 in tRNAs. We identified four atypical H/ACA RNAs that lack the lower stem and the ACA motif and confirmed their function both in vivo and in vitro. Intriguingly, atypical H/ACA RNAs can be modified by Cbf5 in a guide-independent manner. Our data provide the first global view of pseudouridylation in archaea and reveal unexpected structures, substrates, and activities of archaeal H/ACA RNPs.

Bi-allelic human TEKT3 mutations cause male infertility with oligoasthenoteratozoospermia owing to acrosomal hypoplasia and reduced progressive motility.

Oligoasthenoteratozoospermia (OAT) can result in male infertility owing to reduced sperm motility and abnormal spermatozoan morphology. The Tektins are a family of highly conserved filamentous proteins expressed in the axoneme and associated structures in many different metazoan species. Earlier studies on mice identified Tektin3 (Tekt3) as a testis-enriched gene, and knockout of Tekt3 resulted in asthenozoospermia in the mice. Here, whole-exome sequencing of 100 males with asthenozoospermia from unrelated families was performed, followed by Sanger sequencing, leading to the identification of TEKT3 as a candidate gene in two of these patients and their associated family members. In total, three mutations in the TEKT3 gene were identified in both these patients, including one homozygous deletion-insertion mutation (c.543_547delinsTTGAT: p.Glu182*) and one compound heterozygous mutation (c.[548G > A]; [752A > C], p.[Arg183Gln]; [Gln251Pro]). Both of these mutations resulted in the complete loss of TEKT3 expression. The patients were both found to produce sperm that, although those showed no apparent defects in the flagellar structure, had reduced progressive motility. In contrast to mice, most sperm from these two patients exhibited acrosomal hypoplasia, although this did not prevent the use of the sperm for in vitro fertilization through an ICSI approach. TEKT3 was found to bind to other TEKT proteins, suggesting that these proteins form a complex within human spermatozoa. Overall, these results suggest that a loss of TEKT3 function can contribute to OAT incidence in humans. TEKT3 deficiencies can reduce sperm motility and contribute to severe acrosomal hypoplasia in spermatozoa, compromising their normal function.

The evolutionary path of chemosensory and flagellar macromolecular machines in Campylobacterota.

The evolution of macromolecular complex is a fundamental biological question, which is related to the origin of life and also guides our practice in synthetic biology. The chemosensory system is one of the complex structures that evolved very early in bacteria and displays enormous diversity and complexity in terms of composition and array structure in modern species. However, how the diversity and complexity of the chemosensory system evolved remains unclear. Here, using the Campylobacterota phylum with a robust "eco-evo" framework, we investigated the co-evolution of the chemosensory system and one of its important signaling outputs, flagellar machinery. Our analyses show that substantial flagellar gene alterations will lead to switch of its primary chemosensory class from one to another, or result in a hybrid of two classes. Unexpectedly, we discovered that the high-torque generating flagellar motor structure of Campylobacter jejuni and Helicobacter pylori likely evolved in the last common ancestor of the Campylobacterota phylum. Later lineages that experienced significant flagellar alterations lost some key components of complex scaffolding structures, thus derived simpler structures than their ancestor. Overall, this study revealed the co-evolutionary path of the chemosensory system and flagellar system, and highlights that the evolution of flagellar structural complexity requires more investigation in the Bacteria domain based on a resolved phylogenetic framework, with no assumptions on the evolutionary direction.

Modified Ion Migration via Multi-Ion Competitive Transportation for Stable Aqueous Zn Metal Batteries.

The application of metal batteries is seriously affected by active ions transport and deposition stability during operation. This article takes water-based Zn metal electrodes as an example to analyze the factors that affect ion distribution and the impact of ion distribution on electrodeposition morphology through electrochemical model simulation calculation, in situ observation and electrochemical experiment: 1) high concentration will reduce the concentration polarization and the overpotential; 2) The passage of active ions through channels are facilitated by small anion (Cl-) rather than bigger one (SO4 2-), which means small deposition overpotential; 3) The transportability-reaction properties of cations (Zn2+, Li+, Na+ and H+) depends on their concentration, solvent coordination structure, and the energy changes during redox reactions. Based on the diffusion and reaction properties, a Li+ coupled Zn2+ electrolyte is designed to achieve the rapid transportation of doped ions to cover uneven growth sites and maintain a stable interface for the steady deposition of active Zn2+, guiding the interface design for high stability metal batteries in addition to the traditional addition of organic solvents.

Critical Residues Involved in the Coassembly of L1 and L2 Capsid Proteins of Human Papillomavirus 16.

Human papillomaviruses (HPV) are small DNA viruses associated with cervical cancer, warts, and other epithelial tumors. Structural studies have shown that the HPV capsid consists of 360 copies of the major capsid protein, L1, arranged as 72 pentamers in a T=7 icosahedral lattice, coassembling with substoichiometric amounts of the minor capsid protein, L2. However, the residues involved in the coassembly of L1 and L2 remain undefined due to the lack of structure information. Here, we investigated the solvent accessibility surfaces (SASs) of the central cavity residues of the HPV16 L1 pentamer in the crystal structure because those internal exposed residues might mediate the association with L2. Twenty residues in L1 protein were selected to be analyzed, with four residues in the lumen of the L1 pentamer identified as important: F256, R315, Q317, and T340. Mutations to these four residues reduced the PsV (pseudovirus) infection capacity in 293FT cells, and mutations to R315, Q317, and T340 substantially perturb L2 from coassembling into L1 capsid. Compared with wild-type (WT) PsVs, these mutant PsVs also have a reduced ability to become internalized into host cells. Finally, we identified a stretch of negatively charged residues on L2 (amino acids [aa] 337 to 340 [EEIE]), mutations to which completely abrogate L2 assembly into L1 capsid and subsequently impair the endocytosis and infectivity of HPV16 PsVs. These findings shed light on the elusive coassembly between HPV L1 and L2. IMPORTANCE Over 200 types of HPV have been isolated, with several high-risk types correlated with the occurrence of cervical cancer. The HPV major capsid protein, L1, assembles into a T=7 icosahedral viral shell, and associates with the minor capsid protein, L2, which plays a critical role in the HPV life cycle. Despite the important role of the L2 protein, its structure and coassembly with L1 remain elusive. In this study, we analyzed the amino acid residues at the proposed interface between L1 and L2. Certain mutations at these sites decreased the amount of L2 protein assembled into the capsid, which, in turn, led to a decrease in viral infectivity. Knowledge about these residues and the coassembly of L1 and L2 could help to expand our understanding of HPV biology and aid in the development of countermeasures against a wide range of HPV types by targeting the L2 protein.

Dietary branched-chain amino acids intake and new-onset hypertension: a nationwide prospective cohort study in China.

OBJECTIVE: This study aimed to investigate the relationship between dietary branched-chain amino acids (BCAAs) and the risk of developing hypertension. METHODS: A cohort study of 14,883 Chinese adults without hypertension at baseline with were followed for an average of 8.9 years. Dietary intakes of BCAAs, including Ile, Leu, and Val, were collected using 3-day 24-h meal recall and household condiment weighing. Cox proportional hazards regression, restricted cubic splines, interaction analysis, and sensitivity analysis were used to assess the relationship between dietary BCAAs and risk of developing self-reported hypertension, adjusting for age, gender, region, body mass index (BMI), smoking and drinking status, physical activity, energy intake, salt intake. RESULTS: Among 14,883 study subjects, 6386(42.9%) subjects aged ≥ 45 years at baseline, 2692 (18.1%) had new-onset hypertension during the study period, with a median age of 56 years. High levels of dietary BCAAs were associated with an increased risk of new-onset hypertension. Compared with the 41st-60th percentile, multivariable adjusted hazard ratio (HR) for new-onset hypertension was 1.16 (95% CI 1.01-1.32) for dietary BCAAs 61st-80th percentiles, 1.30 (1.13-1.50) for 81st-95th, 1.60 (1.32-1.95) for 96th-100th. The cut-off value of new-onset hypertension risk, total BCAAs, Ile, Leu, and Val were 15.7 g/day, 4.1 g/day, 6.9 g/day, 4.6 g/day, respectively, and the proportion of the population above these intake values were 13.9%, 13.1%, 15.4%, and 14.4%, respectively. Age, BMI, and salt intake had an interactive effect on this relationship (P < 0.001). CONCLUSION: There was a significant positive association between total dietary BCAAs, Ile, Leu, Val intake and the risk of developing hypertension, after adjustment for confounders. This relationship was influenced by age, BMI, and salt intake. Further research is needed to clarify the mechanism and potential role of BCAAs in the pathogenesis of hypertension.

Association of the short-chain fatty acid levels and dietary quality with type 2 diabetes: a case-control study based on Henan Rural Cohort.

Evidence of the relationship between fecal short-chain fatty acids (SCFA) levels, dietary quality and type 2 diabetes mellitus (T2DM) in rural populations is limited. Here, we aimed to investigate the association between fecal SCFA levels and T2DM and the combined effects of dietar quality on T2DM in rural China. In total, 100 adults were included in the case-control study. Dietary quality was assessed by the Alternate Healthy Eating Index 2010 (AHEI-2010), and SCFA levels were analysed using the GC-MS system. Generalised linear regression was conducted to calculate the OR and 95 % CI to evaluate the effect of SCFA level and dietary quality on the risk of T2DM. Finally, an interaction was used to study the combined effect of SCFA levels and AHEI-2010 scores on T2DM. T2DM participants had lower levels of acetic and butyric acid. Generalised linear regression analysis revealed that the OR (95 % CI) of the highest acetic and butyric acid levels were 0·099 (0·022, 0·441) and 0·210 (0·057, 0·774), respectively, compared with the subjects with the lowest tertile of level. We also observed a significantly lower risk of T2DM with acetic acid levels > 1330·106 µg/g or butyric acid levels > 585·031 µg/g. Moreover, the risks of higher acetic and butyric acid levels of T2DM were 0·007 (95 % CI: 0·001, 0·148), 0·005 (95 % CI: 0·001, 0·120) compared with participants with lower AHEI-2010 scores (all P < 0·05). Acetate and butyrate levels may be important modifiable beneficial factors affecting T2DM in rural China. Improving dietary quality for body metabolism balance should be encouraged to promote good health.

Integrated Analysis of Per- and Polyfluoroalkyl Substance Exposure and Metabolic Profiling of Elderly Residents Living near Industrial Plants.

Per- and polyfluoroalkyl substances (PFASs) are widely used in industrial production, causing potential health risks to the residents living around chemical industrial plants; however, the lack of data on population exposure and adverse effects impedes our understanding and ability to prevent risks. In this study, we performed screening and association analysis on exogenous PFAS pollutants and endogenous small-molecule metabolites in the serum of elderly residents living near industrial plants. Exposure levels of 11 legacy and novel PFASs were determined. PFOA and PFOS were major contributors, and PFNA, PFHxS, and 6:2 Cl-PFESA also showed high detection frequencies. Association analysis among PFASs and 287 metabolites identified via non-target screening was performed with adjustments of covariates and false discovery rate. Strongly associated metabolites were predominantly lipid and lipid-like molecules. Steroid hormone biosynthesis, primary bile acid biosynthesis, and fatty-acid-related pathways, including biosynthesis of unsaturated fatty acids, linoleic acid metabolism, α-linolenic acid metabolism, and fatty acid biosynthesis, were enriched as the metabolic pathways associated with mixed exposure to multiple PFASs, providing metabolic explanation and evidence for the potential mediating role of adverse health effects as a result of PFAS exposure. Our study achieved a comprehensive screening of PFAS exposure and associated metabolic profiling, demonstrating the promising application for integrated analysis of exposome and metabolome.

Association of short-chain fatty acids and the gut microbiome with type 2 diabetes: Evidence from the Henan Rural Cohort.

BACKGROUND AND AIMS: Human studies about short-chain fatty acids (SCFAs), the gut microbiome, and Type 2 diabetes (T2DM) are limited. Here we explored the association between SCFAs and T2DM and the effects of gut microbial diversity on glucose status in rural populations. METHODS AND RESULTS: We performed a cross-sectional study from the Henan Rural Cohort and collected stool samples. Gut microbiota composition and faecal SCFA concentrations were measured by 16S rRNA and GC-MS. The population was divided based on the tertiles of SCFAs, and logistic regression models assessed the relationship between SCFAs and T2DM. Generalized linear models tested the interactions between SCFAs and gut microbial diversity on glucose indicators (glucose, HbAlc and insulin). Compared to the lowest tertile of total SCFA, acetate and butyrate, the highest tertile exhibited lower T2DM prevalence, with ORs and 95% CIs of 0.291 (0.085-0.991), 0.160 (0.044-0.574) and 0.171 (0.047-0.620), respectively. Restricted cubic spline demonstrated an approximately inverse S-shaped association. We also noted interactions of the ACE index with the highest tertile of valerate on glucose levels (P-interaction = 0.022) and the Shannon index with the middle tertile of butyrate on insulin levels (P-interaction = 0.034). Genus Prevotella_9 and Odoribacter were inversely correlated with T2DM, and the genus Blautia was positively associated with T2DM. These bacteria are common SCFA-producing members. CONCLUSIONS: Inverse S-shaped associations between SCFAs (total SCFA, acetate, and butyrate) and T2DM were observed. Valerate and butyrate modify glucose status with increasing gut microbial diversity.

Watermelon Flesh-Like Ni3 S2 @C Composite Separator with Polysulfide Shuttle Inhibition for High-Performance Lithium-Sulfur Batteries.

The shuttle effect limits the practical application of lithium-sulfur (Li-S) batteries with high specific capacity and cheap price. Herein, a three-dimensional carbon substrate containing Ni3 S2 nanoparticles is created to modify the separator. The in situ optical visualization battery proves that the material can realize the rapid conversion of Li2 S6 . Moreover, the impact of lithium-ion diffusion on the reactions in the cell is investigated, and the mechanism of Ni3 S2 @C in the cell is proposed based on the "adsorption-diffusion-conversion" mechanism. The "adsorption-diffusion-conversion" process of polysulfide is carried out on the surface of the composite separator, showing positive effects on the inhibition of polysulfide shuttle and the promotion of conversion. The separator is modified to improve sulfur utilization and reduce dead sulfur accumulation through a strategy of chemical immobilization and physical blocking. This helps to bridge the existing gaps of Li-S batteries.

LRRC23 deficiency causes male infertility with idiopathic asthenozoospermia by disrupting the assembly of radial spokes.

Asthenozoospermia (AZS) is the primary cause of infertility in males. The radial spoke (RS) is an axonemal structure, connecting the peripheral doublet microtubules with the central pair of microtubules. This T-shaped multiprotein complex functions as a mechanochemical sensor to promote sperm motility. LRRC23 is a novel subunit of the RS complex that is necessary for flagellar assembly and movement in mice. However, the importance of LRRC23 in modulating RS formation in humans remains unclear. Here, we identified a homozygous nonsense mutation in LRRC23 (c.376C>T:p. Arg126X) in an infertile AZS patient whose parents were consanguineous. We verified the adversity of this novel mutation because of its ability to disrupt LRRC23 synthesis and impair RSs integrity. Furthermore, we demonstrated an interaction between LRRC23 and RSPH3 in vitro, indicating that LCCR23 is associated with RS in humans. Meanwhile, the LRRC23-mutant patient had a good prognosis following intracytoplasmic sperm injection. This study provides strong preliminary evidence that LRRC23 defects are potential causative factors of AZS in humans, which expands our knowledge for improved genetic counseling and better reproductive recommendations for patients with AZS.

ACROSIN deficiency causes total fertilization failure in humans by preventing the sperm from penetrating the zona pellucida.

STUDY QUESTION: Does a homozygous nonsense mutation in ACR lead to total fertilization failure (TFF) resulting in male infertility in humans? SUMMARY ANSWER: A novel homozygous nonsense mutation of ACR (c.167G>A, p.Trp56X) was identified in two infertile brothers and shown to cause human TFF. WHAT IS KNOWN ALREADY: ACROSIN, encoded by ACR, is a major acrosomal enzyme expressed only in the acrosome of the sperm head. Inhibition of acrosin prevents sperm penetration of the zona pellucida (ZP) in several species, including humans. Acr-knockout in hamsters causes male infertility with completely blocked fertilization. Of note, there are no reports of ACR mutations associated with TFF in humans. STUDY DESIGN, SIZE, DURATION: Whole-exome sequencing (WES) was used for the identification of pathogenic genes for male factor TFF in eight involved couples. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from eight infertile couples who had experienced TFF during their IVF or ICSI attempts were collected. Functional assays were used to verify the pathogenicity of the potential genetic factors identified by WES. Subzonal insemination (SUZI) and IVF assays were performed to determine the exact pathogenesis of TFF caused by deficiencies in ACROSIN. MAIN RESULTS AND THE ROLE OF CHANCE: A novel homozygous nonsense mutation in ACR, c.167G>A, p.Trp56X, was identified in two additional primary infertile brothers whose parents were first cousins. This rare mutation caused ACROSIN deficiency and acrosomal ultrastructural defects in the affected sperm. Spermatozoa lacking ACROSIN were unable to penetrate the ZP, rather than hampering sperm binding, disrupting gamete fusion, or preventing oocyte activation. These findings were supported by the fertilization success of SUZI and ICSI attempts, as well as the normal expression of ACTL7A and PLCζ in the mutant sperm, suggesting that ICSI without remedial assisted oocyte activation is an optimal treatment for ARCOSIN-deficient TFF. LIMITATIONS, REASONS FOR CAUTION: The absence of another independent pedigree to support our argument is a limitation of this study. WIDER IMPLICATIONS OF THE FINDINGS: The findings expand our understanding of the genes involved in human TFF, providing information for appropriate genetic counseling and fertility guidance for these patients. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Natural Science Foundation of China (grant no. 82201803, 81901541, 82271639, and 32000584), University Synergy Innovation Program of Anhui Province (GXXT-2019-044), and the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences (grant no. 2019PT310002). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Identification of a genomic region linked with sex determination of Undaria pinnatifida (Alariaceae) through genomic resequencing and genetic linkage analyses of a segregating gametophyte family.

Different from the traditional knowledge about kelp, three sexual phenotypes (female, male, and monoecious) exist in the haploid gametophytes of Undaria pinnatifida. However, the sex-determining mechanisms remain unknown. Genetic linkage mapping is an efficient tool to identify sex-linked regions. In the present study, we resequenced a segregating gametophyte family based on the male genome of U. pinnatifida. A high-density genetic linkage map was constructed using 9887 SNPs, with an average distance of 0.41 cM between adjacent SNPs. On the basis of this genetic map and using the composite interval mapping method, we identified 62 SNPs significantly linked with the sexual phenotype. They were located at a position of 67.67 cM on the linkage group 23, corresponding to a physical range of 14.67 Mbp on the HiC_Scaffold_23 of the genome. Reanalysis of the previous specific length amplified fragment sequencing data according to the reference genome led to the identification of a sex-linked genomic region that encompassed the above-mentioned 14.67 Mbp region. Hence, this overlapped genomic range was likely the sex-determining region. Within this region, 129 genes were retrieved and 39 of them were annotated with explicit function, including the potential male sex-determining gene-encoding high mobility group (HMG) domain protein. Relative expression analysis of the HMG gene showed that its expression was higher in male gametophytes during the vegetative phase and monoecious gametophytes during both the vegetative and gametogenesis phases, but significantly lower in male gametophytes during the gametogenesis phase. These results provide a foundation for deciphering the sex-determining mechanism of U. pinnatifida.

Genetic prediction of age at menarche, age at natural menopause and type 2 diabetes: A Mendelian randomization study.

BACKGROUND AND AIMS: The relationship between reproductive factors and type 2 diabetes (T2D) is controversial; therefore, we explored the causal relationship of age at menarche (AAM), age at natural menopause (ANM), with the risk of T2D and glycemic traits using two-sample Mendelian randomization. METHODS AND RESULTS: We used publicly available data at the summary level of genome-wide association studies, where AAM (N = 329,345), ANM (N = 69,360), T2D (N = 464,389). The inverse variance weighting (IVW) method was employed as the primary method. To demonstrate the robustness of the results, we also conducted various sensitivity analysis methods including the MR-Egger regression, the weighted median (WM) and the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. After excluding IVs associated with confounders, we found a causal association between later AAM and reduced risk of T2D (OR 0.81 [95% CI 0.75, 0.87]; P = 2.20 × 10-8), lower levels of FI (ß -0.04 [95% CI -0.06, -0.01]; P = 2.19 × 10-3), FPG (ß -0.03 [95% CI -0.05, -0.007]; P = 9.67 × 10-5) and HOMA-IR (ß -0.04 [95% CI -0.06, -0.01]; P = 4,95 × 10-3). As for ANM, we only found a causal effect with HOMA-IR (ß -0.01 [95% CI -0.02, -0.005]; P = 1.77 × 10-3), but not with T2D. CONCLUSIONS: Our MR study showed a causal relationship between later AAM and lower risk of developing T2D, lower FI, FPG and HOMA-IR levels. This may provide new insights into the prevention of T2D in women.

Associations between healthy lifestyle score and health-related quality of life among Chinese rural adults: variations in age, sex, education level, and income.

PURPOSE: This study aimed to investigate the associations between overall lifestyles and HRQoL, as well as the variations in age, sex, education level, and income. METHODS: A total of 23,402 participants from the Henan rural cohort were included. The healthy lifestyle score (HLS) consists of five lifestyle factors: smoking, alcohol drinking, physical activity, diet, and body mass index. HRQoL was assessed by the EQ-5D-5L questionnaire. The general linear model and Tobit regression model were utilized to assess the associations of HLS with visual analogue score (VAS) and utility index. RESULTS: Compared with participants with an HLS of 0-2, the corresponding regression coefficients (ß) and 95% confidence intervals (CI) of participants with an HLS of 3, 4, and 5 for VAS score were 1.09 (0.59, 1.59), 1.92 (1.38, 2.46), and 2.60 (1.83, 3.37); the corresponding ß and 95% CI for utility index were 0.02 (0.01, 0.03), 0.05 (0.03, 0.06), and 0.06 (0.04, 0.07). Notably, these positive associations were greater among the elderly, female, and those with lower education level and average monthly income (p for interaction < 0.05). For instance, the corresponding ß and 95% CI of individuals with an HLS of 5 for utility index in average monthly income < 500 RMB, 500-999 RMB, and ≥ 1000 RMB groups were 0.08 (0.05, 0.11), 0.06 (0.03, 0.09), and 0.02 (- 0.00, 0.05). CONCLUSION: Engaging in healthier lifestyle habits was associated with a higher level of HRQoL, especially in the elderly, females, and those with low education level and average monthly income.

Association between snoring, daytime sleepiness and cardiovascular disease in Chinese rural adults.

BACKGROUNDS AND AIMS: Evidence on the association between habitual snoring, excessive daytime sleepiness (EDS), and cardiovascular diseases (CVDs) remains uncertain and limited. The study aimed to explore the independent and joint association between habitual snoring, EDS, and CVDs in rural Chinese adults. METHODS AND RESULTS: A total of 28,140 participants from the Henan rural cohort study were included. Sleep status information was obtained by self-reported. Based on their sleep status, the participants were classified into four groups: "no snoring and no EDS (NSNS) (reference group)", "snoring and no EDS (SNS)", "no snoring and EDS (NSS)", "snoring and EDS (SS)." The logistic regression models were used to calculate independent and joint odds ratios (OR) and 95% confidence intervals (CI) between the snoring, EDS status and stroke, CHD, and CVD. Of the 28,140 participants, 740 subjects reported snoring and sleepiness. The ORs and (95% CIs) for CVDs in the adjusted model were 1.31 (1.20-1.43) for participants who snored frequently and 2.44 (1.76-3.39) for frequent sleepiness compared with no snoring and no sleepiness. Individuals with both snoring and sleepiness had higher odds of CVDs compared with no snoring and no sleepiness (OR: 2.18, 95%CI: 1.80-2.62). CONCLUSION: Habitual snoring and excessive daytime sleepiness were independently and jointly associated with CVDs in the Chinese rural population. More studies are needed to explore the mechanisms of the relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-52 07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.

Omics-guided bacterial engineering of Escherichia coli ER2566 for recombinant protein expression.

The goal of bacterial engineering is to rewire metabolic pathways to generate high-value molecules for various applications. However, the production of recombinant proteins is constrained by the complexity of the connections between cellular physiology and recombinant protein synthesis. Here, we used a rational and highly efficient approach to improve bacterial engineering. Based on the complete genome and annotation information of the Escherichia coli ER2566 strain, we compared the transcriptomic profiles of the strain under leaky expression and low temperature-induced stress. Combining the gene ontology (GO) enrichment terms and differentially expressed genes (DEGs) with higher expression, we selected and knocked out 36 genes to determine the potential impact of these genes on protein production. Deletion of bluF, cydA, mngR, and udp led to a significant decrease in soluble recombinant protein production. Moreover, at low-temperature induction, 4 DEGs (gntK, flgH, flgK, flgL) were associated with enhanced expression of the recombinant protein. Knocking out several motility-related DEGs (ER2666-ΔflgH-ΔflgL-ΔflgK) simultaneously improved the protein yield by 1.5-fold at 24 °C induction, and the recombinant strain had the potential to be applied in the expression studies of different exogenous proteins, aiming to improve the yields of soluble form to varying degrees in comparison to the ER2566 strain. Totally, this study focused on the anabolic and stress-responsive hub genes of the adaptation of E. coli to recombinant protein overexpression on the transcriptome level and constructs a series of engineering strains increasing the soluble protein yield of recombinant proteins which lays a solid foundation for the engineering of bacterial strains for recombinant technological advances. KEY POINTS: • Comparative transcriptome analysis shows host responses with altered induction stress. • Deletion of bluF, cydA, mngR, and udp genes was identified to significantly decrease the soluble recombinant protein productions. • Synchronal knockout of flagellar genes in E. coli can enhance recombinant protein yield up to ~ 1.5-fold at 24 °C induction. • Non-model bacterial strains can be re-engineered for recombinant protein expression.

Association between dietary approaches to stop hypertension (DASH) diet and hyperuricemia among Chinese adults: findings from a nationwide representative study.

BACKGROUND: Certain foods and food groups could positively or negatively impact serum uric acid (SUA) levels. However, evidence on the holistic dietary strategy to prevent and control hyperuricemia (HUA) development remains limited. OBJECTIVE: The aim of this research work was to explore the association of dietary approaches to stop hypertension (DASH) diet with SUA levels and odds of HUA among Chinese adults. METHODS: This research premise included 66,427 Chinese adults aged 18 and above who were part of the China Adult Chronic Disease and Nutrition Surveillance in 2015. Dietary consumptions were assessed via the household condiment weighing approach and a three-day, 24-hour dietary recall. Total fat, saturated fat, calcium, protein, potassium, cholesterol, magnesium, fiber, and sodium were all adopted to calculate the DASH score (score range, 0-9). The associations of DASH score with SUA levels and odds of HUA were evaluated using multiple linear and logistic regression models, respectively. RESULTS: We established that a higher DASH score was linked with a lower SUA levels (ß = - 0.11; 95% CI: - 0.12, - 0.1; p < 0.001) and odds of HUA (OR = 0.85; 95% CI: 0.83, 0.87; p < 0.001) after adjustment for age, sex, ethnicity, education status, marital status, health behaviours and health factors. The association of the DASH diet with odds of HUA was stronger among men (p-interaction = 0.009), non-Han Chinese (p-interaction< 0.001) as well as rural residents (p-interaction< 0.001). CONCLUSIONS: Our results illustrate that the DASH diet was remarkably negatively with SUA levels and odds of HUA in the Chinese adult population.

High quality stealth dicing of sapphire with a picosecond Bessel beam by controlling the polarization direction.

Sapphire is an important substrate material in optoelectronic devices, and it is also widely used as a touch screen panel. In order to achieve high quality cutting of sapphire, the stealth dicing of 500 µm thick sapphire by a picosecond Bessel beam is studied in this paper. The influences of laser polarization direction and process parameters on cutting section roughness were studied. By controlling the laser polarization direction, different crack propagation morphologies were obtained. When the polarization direction was vertical to the cutting path, the crack propagation path was straighter, and the sapphire had better cutting quality. The laser processing parameters, including burst mode, hole spacing, and pulse energy, had a significant impact on the cutting section roughness. When the polarization direction was vertical to the cutting path under the optimal process parameters, the cutting section was uniform and flat, with no recondensable particles, no ripples, and no chamfer, and an 89.7 nm average roughness of the cutting section could be obtained.

Alkalihalobacillus deserti sp. nov., Isolated from the Saline-Alkaline Soil.

A bacterial strain, designated TRPH29T, was isolated from saline-alkaline soil, collected from the southern edge of the Gurbantunggut desert, Xinjiang, People's Republic of China. The isolate was Gram-staining positive, facultatively anaerobic, straight rods. Growth occurred at 15-40 °C (optimum, 28 °C), pH 8.0-13.0 (optimum, 10.0), and in the presence of 0-15% (w/v) NaCl (optimum, 2%). Phylogenetic analysis using 16S rRNA gene sequence indicated that strain TRPH29T showed the highest sequence similarities to Alkalihalobacillus krulwichiae (98.31%), Alkalihalobacillus wakoensis (98.04%), and Alkalihalobacillus akibai (97.69%). Average nucleotide identity (ANI) and digital DNA-DNA hybridization values between strain TRPH29T and Alkalihalobacillus krulwichiae, Alkalihalobacillus wakoensis, Alkalihalobacillus akibai were in the range of 73.62-75.52% and 15.0-21.20%, respectively. Results of genome analyses indicated that the genome size of strain TRPH29T was 5.05 Mb, with a genomic DNA G + C content of 37.30%. Analysis of the cellular component of strain TRPH29T revealed that the primary fatty acids were anteiso-C15:0 and iso-C15:0, and the polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified glycolipid, and an unidentified phospholipid. The predominant respiratory quinone was MK-7. Based on the genomic, phylogenetic, phenotypic and chemotaxonomic analyses, strain TRPH29T represents a novel species of the genus Alkalihalobacillus, for which the name Alkalihalobacillus deserti sp. nov. is proposed. The type strain is TRPH29T (= CGMCC 1.19067T = NBRC 115475T).