Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Temperature, pH, and oxygen availability contributed to the functional differentiation of ancient Nitrososphaeria.

Ammonia-oxidizing Nitrososphaeria are among the most abundant archaea on Earth and have profound impacts on the biogeochemical cycles of carbon and nitrogen. In contrast to these well-studied ammonia-oxidizing archaea (AOA), deep-branching non-AOA within this class remain poorly characterized because of a low number of genome representatives. Here, we reconstructed 128 Nitrososphaeria metagenome-assembled genomes from acid mine drainage and hot spring sediment metagenomes. Comparative genomics revealed that extant non-AOA are functionally diverse, with capacity for carbon fixation, carbon monoxide oxidation, methanogenesis, and respiratory pathways including oxygen, nitrate, sulfur, or sulfate, as potential terminal electron acceptors. Despite their diverse anaerobic pathways, evolutionary history inference suggested that the common ancestor of Nitrososphaeria was likely an aerobic thermophile. We further surmise that the functional differentiation of Nitrososphaeria was primarily shaped by oxygen, pH, and temperature, with the acquisition of pathways for carbon, nitrogen, and sulfur metabolism. Our study provides a more holistic and less biased understanding of the diversity, ecology, and deep evolution of the globally abundant Nitrososphaeria.

Metagenomic Discovery of "Candidatus Parvarchaeales"-Related Lineages Sheds Light on Adaptation and Diversification from Neutral-Thermal to Acidic-Mesothermal Environments.

"Candidatus Parvarchaeales" microbes, representing a DPANN archaeal group with limited metabolic potential and reliance on hosts for their growth, were initially found in acid mine drainage (AMD). Due to the lack of representatives, however, their ecological roles and adaptation to extreme habitats such as AMD as well as how they diverge across the lineage remain largely unexplored. By applying genome-resolved metagenomics, 28 Parvarchaeales-associated metagenome-assembled genomes (MAGs) representing two orders and five genera were recovered. Among them, we identified three new genera and proposed the names "Candidatus Jingweiarchaeum," "Candidatus Haiyanarchaeum," and "Candidatus Rehaiarchaeum," with the former two belonging to a new order, "Candidatus Jingweiarchaeales." Further analyses of the metabolic potentials revealed substantial niche differentiation between Jingweiarchaeales and Parvarchaeales. Jingweiarchaeales may rely on fermentation, salvage pathways, partial glycolysis, and the pentose phosphate pathway (PPP) for energy conservation reservation, while the metabolic potentials of Parvarchaeales might be more versatile. Comparative genomic analyses suggested that Jingweiarchaeales favor habitats with higher temperatures and that Parvarchaeales are better adapted to acidic environments. We further revealed that the thermal adaptation of these lineages, especially Haiyanarchaeum, might rely on genomic features such as the usage of specific amino acids, genome streamlining, and hyperthermophile featured genes such as rgy. Notably, the adaptation of Parvarchaeales to acidic environments was possibly driven by horizontal gene transfer (HGT). The reconstruction of ancestral states demonstrated that both may have originated from thermal and neutral environments and later spread to mesothermal and acidic environments. These evolutionary processes may also be accompanied by adaptation to oxygen-rich environments via HGT. IMPORTANCE "Candidatus Parvarchaeales" microbes may represent a lineage uniquely distributed in extreme environments such as AMD and hot springs. However, little is known about the strategies and processes of how they adapted to these extreme environments. By the discovery of potential new order-level lineages, "Ca. Jingweiarchaeales," and in-depth comparative genomic analysis, we unveiled the functional differentiation of these lineages. Furthermore, we show that the adaptation of these lineages to high-temperature and acidic environments was driven by different strategies, with the former relying more on genomic characteristics such as genome streamlining and amino acid compositions and the latter relying more on the acquisition of genes associated with acid tolerance. Finally, by the reconstruction of the ancestral states of the optimal growth temperature (OGT) and isoelectric point (pI), we showed the potential evolutionary process of Parvarchaeales-related lineages with regard to the shift from the high-temperature environment of their common ancestors to low-temperature (potentially acidic) environments.

Bacteriophage Therapy as an Application for Bacterial Infection in China.

Antibiotic resistance has emerged as a significant issue to be resolved around the world. Bacteriophage (phage), in contrast to antibiotics, can only kill the target bacteria with no adverse effect on the normal bacterial flora. In this review, we described the biological characteristics of phage, and summarized the phage application in China, including in mammals, ovipara, aquatilia, and human clinical treatment. The data showed that phage had a good therapeutic effect on drug-resistant bacteria in veterinary fields, as well as in the clinical treatment of humans. However, we need to take more consideration of the narrow lysis spectrum, the immune response, the issues of storage, and the pharmacokinetics of phages. Due to the particularity of bacteriophage as a bacterial virus, there is no unified standard or regulation for the use of bacteriophage in the world at present, which hinders the application of bacteriophage as a substitute for antibiotic biological products. We aimed to highlight the rapidly advancing field of phage therapy as well as the challenges that China faces in reducing its reliance on antibiotics.

Panguiarchaeum symbiosum, a potential hyperthermophilic symbiont in the TACK superphylum.

The biology of Korarchaeia remains elusive due to the lack of genome representatives. Here, we reconstruct 10 closely related metagenome-assembled genomes from hot spring habitats and place them into a single species, proposed herein as Panguiarchaeum symbiosum. Functional investigation suggests that Panguiarchaeum symbiosum is strictly anaerobic and grows exclusively in thermal habitats by fermenting peptides coupled with sulfide and hydrogen production to dispose of electrons. Due to its inability to biosynthesize archaeal membranes, amino acids, and purines, this species likely exists in a symbiotic lifestyle similar to DPANN archaea. Population metagenomics and metatranscriptomic analyses demonstrated that genes associated with amino acid/peptide uptake and cell attachment exhibited positive selection and were highly expressed, supporting the proposed proteolytic catabolism and symbiotic lifestyle. Our study sheds light on the metabolism, evolution, and potential symbiotic lifestyle of Panguiarchaeum symbiosum, which may be a unique host-dependent archaeon within the TACK superphylum.

Electrochemical Reduction and Preparation of Cu-Se Thermoelectric Thin Film in Solutions with PEG.

Investigation of Cu(II) and Se(IV) electrochemical reduction processes in solutions with poly(ethylene glycol) (PEG) provides important theoretical guidance for the preparation of Cu-Se alloy films with stronger thermoelectric properties. The results reveal that PEG adsorbing on the electrode surface does not affect the electrochemical reduction mechanism of Cu(II), Se(IV), and Cu(II)-Se(IV), but inhibits the electrochemical reduction rates. The surface morphology and composition change with a negative shift in the deposition potentials. The Cu-Se alloy film, which was prepared at 0.04 V, was α-Cu2Se as-deposited and P-type thermoelectric material after annealing. The highest thermoelectric properties were as follows: Seebeck coefficient (α) was +106 µV·K-1 and 1.89 times of Cu-Se alloy film electrodeposited in Cu(II)-Se(IV) binary solution without PEG; resistivity (ρ) was 2.12 × 10-3 Ω·cm, and the calculated power factor (PF) was 5.3 µW·cm-1K-2 and 4.07 times that without PEG.

Lytic Bacteriophage PZL-Ah152 as Biocontrol Measures Against Lethal Aeromonas hydrophila Without Distorting Gut Microbiota.

Phage therapy is an alternative approach to overcome the problem of multidrug resistance in bacteria. In this study, a bacteriophage named PZL-Ah152, which infects Aeromonas hydrophila, was isolated from sewage, and its biological characteristics and genome were studied. The genome contained 54 putative coding sequences and lacked known putative virulence factors, so it could be applied to phage therapy. Therefore, we performed a study to (i) investigate the efficacy of PZL-Ah152 in reducing the abundance of pathogenic A. hydrophila strain 152 in experimentally infected crucian carps, (ii) evaluate the safety of 12 consecutive days of intraperitoneal phage injection in crucian carps, and (iii) determine how bacteriophages impact the normal gut microbiota. The in vivo and in vitro results indicated that the phage could effectively eliminate A. hydrophila. Administering PZL-Ah152 (2 × 109 PFU) could effectively protect the fish (2 × 108 CFU/carp). Furthermore, a 12-day consecutive injection of PZL-Ah152 did not cause significant adverse effects in the main organs of the treated animals. We also found that members of the genus Aeromonas could enter and colonize the gut. The phage PZL-Ah152 reduced the number of colonies of the genus Aeromonas. However, no significant changes were observed in α-diversity and ß-diversity parameters, which suggested that the consumed phage had little effect on the gut microbiota. All the results illustrated that PZL-Ah152 could be a new therapeutic method for infections caused by A. hydrophila.

Characterization and genome analysis of two new Aeromonas hydrophila phages, PZL-Ah1and PZL-Ah8.

Aeromonas hydrophila (A. hydrophila) is an opportunistic pathogen of fish, humans, and livestock, and has a severe negative impact on aquaculture development. Phage therapy is considered an alternative strategy for controlling bacterial infections and contamination. In this study, we isolated and characterized the genomes of two A. hydrophila-specific phages, PZL-Ah1 and PZL-Ah8, which, based on transmission electron microscopy, were identified as members of the family Podoviridae. Both of these phages had a relatively narrow host range, with lytic activity against Aeromonas spp. strains. Whole-genome sequence analysis revealed that PZL-Ah1 and PZL-Ah8 have a double-stranded DNA genome of 38,641 bp and 40,855 bp in length, with a GC content of 53.68% and 51.89%, respectively. Forty-four open reading frames (ORFs) were predicted in PZL-Ah1, and 52 were predicted in PZL-Ah8. Twenty-eight (63.6%) ORFs in PZL-Ah1 and 29 (55.8%) ORFs in PZL-Ah8 were predicted to encode functional proteins with homologs in the NCBI database, while the remaining ORFs were classified as encoding hypothetical proteins with unknown functions. A comparison with known phage genes suggested that ORF 02, ORF 29, and ORF 04 of PZL-Ah1 and ORF 2 and ORF 4 of PZL-Ah8 are involved in host cell lysis. This study expands the phage genome database and provides good candidates for phage typing applications.

Aeromonas veronii virulence and adhesion attenuation mediated by the gene aodp.

Aeromonas veronii (A. veronii) is an opportunistic pathogen of fish-human-livestock, which poses a threat to the development of aquaculture. Based on our previous studies on proteomics and genomics, we found out that the aodp gene may be related to the virulence of A. veronii TH0426. However, aodp gene encodes a hypothetical protein with an unknown function, and its role in A. veronii TH0426 is not clear. Here, we first constructed a mutant strain (△-aodp) to investigate the functional role of aodp in A. veronii TH0426. Compared with the wild strain A. veronii TH0426, the growth rate of strain △-aodp was slower and was resistant to neomycin and kanamycin, but sensitive to cephalexin. The swimming and swarming ability of △-aodp strain decreased, and the pathogenicity to mice decreased by 15.84-fold. Besides, the activity of caspase-3 in EPCs infected with △-aodp strain was 1.49-fold lower than that of the wild strain. We examined 20 factors closely related to A. veronii virulence, among them 17 genes were down-regulated as a result of aodp deficiency. This study laid a foundation for further studies on the pathogenesis of A. veronii.

A phage cocktail in controlling phage resistance development in multidrug resistant Aeromonas hydrophila with great therapeutic potential.

Aeromonas hydrophila (A. hydrophila) is an opportunistic pathogen of fish-human-livestock, which poses a threat to the development of aquaculture. Lytic phage has long been considered as an effective bactericidal agent. However, the rapid development of phage resistance seriously hinders the continuous application of lytic phages. In our study, a new bacteriophage vB_ AhaP_PZL-Ah8 was isolated from sewage and its characteristics and genome were investigated. Phage vB_ AhaP_PZL-Ah8 has been classified as the member of the Podoviridae family, which exhibited the latent period was about 30 min. As revealed from the genomic sequence analysis, vB_ AhaP_PZL-Ah8 covered a double-stranded genome of 40,855 bp (exhibiting 51.89% G + C content), with encoding 52 predicted open reading frames (ORFs). The results suggested that the combination of vB_ AhaP_PZL-Ah8 and another A. hydrophila phage vB_ AhaP_PZL-Ah1 could improve the therapeutic efficacy both in vitro and in vivo. The resistance mutation frequency of A. hydrophila cells infected with the mixture phage (vB_ AhaP_PZL-Ah8+ vB_ AhaP_PZL-Ah1) was significantly lower than cells treated with single phage (P <0.01). Phage therapy in vivo showed that the survival rate in the mixture phage treatment group was significantly higher than that in single phage treatment group.

Deciphering Symbiotic Interactions of "Candidatus Aenigmarchaeota" with Inferred Horizontal Gene Transfers and Co-occurrence Networks.

"Candidatus Aenigmarchaeota" ("Ca. Aenigmarchaeota") represents one of the earliest proposed evolutionary branches within the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaeota (DPANN) superphylum. However, their ecological roles and potential host-symbiont interactions are still poorly understood. Here, eight metagenome-assembled genomes (MAGs) were reconstructed from hot spring ecosystems, and further in-depth comparative and evolutionary genomic analyses were conducted on these MAGs and other genomes downloaded from public databases. Although with limited metabolic capacities, we reported that "Ca. Aenigmarchaeota" in thermal environments harbor more genes related to carbohydrate metabolism than "Ca. Aenigmarchaeota" in nonthermal environments. Evolutionary analyses suggested that members from the Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota (TACK) superphylum and Euryarchaeota contribute substantially to the niche expansion of "Ca. Aenigmarchaeota" via horizontal gene transfer (HGT), especially genes related to virus defense and stress responses. Based on co-occurrence network results and recent genetic exchanges among community members, we conjectured that "Ca. Aenigmarchaeota" may be symbionts associated with one MAG affiliated with the genus Pyrobaculum, though host specificity might be wide and variable across different "Ca. Aenigmarchaeota" organisms. This study provides significant insight into possible DPANN-host interactions and ecological roles of "Ca. Aenigmarchaeota." IMPORTANCE Recent advances in sequencing technology promoted the blowout discovery of super tiny microbes in the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota, and Nanohaloarchaeota (DPANN) superphylum. However, the unculturable properties of the majority of microbes impeded our investigation of their behavior and symbiotic lifestyle in the corresponding community. By integrating horizontal gene transfer (HGT) detection and co-occurrence network analysis on "Candidatus Aenigmarchaeota" ("Ca. Aenigmarchaeota"), we made one of the first attempts to infer their putative interaction partners and further decipher the potential functional and genetic interactions between the symbionts. We revealed that HGTs contributed by members from the Thaumarchaeota, Aigarchaeota, Crenarchaeota, and Korarchaeota (TACK) superphylum and Euryarchaeota conferred "Ca. Aenigmarchaeota" with the ability to survive under different environmental stresses, such as virus infection, high temperature, and oxidative stress. This study demonstrates that the interaction partners might be inferable by applying informatics analyses on metagenomic sequencing data.

Comparative Genomics Reveals Thermal Adaptation and a High Metabolic Diversity in "Candidatus Bathyarchaeia".

"Candidatus Bathyarchaeia" is a phylogenetically diverse and widely distributed lineage often in high abundance in anoxic submarine sediments; however, their evolution and ecological roles in terrestrial geothermal habitats are poorly understood. In the present study, 35 Ca. Bathyarchaeia metagenome-assembled genomes (MAGs) were recovered from hot spring sediments in Tibet and Yunnan, China. Phylogenetic analysis revealed all MAGs of Ca. Bathyarchaeia can be classified into 7 orders and 15 families. Among them, 4 families have been first discovered in the present study, significantly expanding the known diversity of Ca. Bathyarchaeia. Comparative genomics demonstrated Ca. Bathyarchaeia MAGs from thermal habitats to encode a large variety of genes related to carbohydrate degradation, which are likely a metabolic adaptation of these organisms to a lifestyle at high temperatures. At least two families are potential methanogens/alkanotrophs, indicating a potential for the catalysis of short-chain hydrocarbons. Three MAGs from Family-7.3 are identified as alkanotrophs due to the detection of an Mcr complex. Family-2 contains the largest number of genes relevant to alkyl-CoM transformation, indicating the potential for methylotrophic methanogenesis, although their evolutionary history suggests the ancestor of Ca. Bathyarchaeia was unable to metabolize alkanes. Subsequent lineages have acquired the ability via horizontal gene transfer. Overall, our study significantly expands our knowledge and understanding of the metabolic capabilities, habitat adaptations, and evolution of Ca. Bathyarchaeia in thermal environments. IMPORTANCE Ca. Bathyarchaeia MAGs from terrestrial hot spring habitats are poorly revealed, though they have been studied extensively in marine ecosystems. In this study, we uncovered the metabolic capabilities and ecological role of Ca. Bathyarchaeia in hot springs and give a comprehensive comparative analysis between thermal and nonthermal habitats to reveal the thermal adaptability of Ca. Bathyarchaeia. Also, we attempt to determine the evolutionary history of methane/alkane metabolism in Ca. Bathyarchaeia, since it appears to be the first archaea beyond Euryarchaeota which contains the mcrABG genes. The reclassification of Ca. Bathyarchaeia and significant genomic differences among different lineages largely expand our knowledge on these cosmopolitan archaea, which will be beneficial in guiding the future studies.

The U-shaped association of altitudes with prevalence of hypertension among residents in Tibet, China.

We aimed to evaluate the association of altitudes with the prevalence of hypertension among residents aged 15 years and above in Tibet, China. Data for 11,407 Tibetan residents from the National Health Services Survey in 2013 were analyzed. Association between altitudes and prevalence of physician-diagnosed hypertension was assessed by two logistic regression models as follows: (i) a base model adjusted for age and gender, and (ii) a full model additionally adjusted for body mass index, education, marital status, area of residence, distance to the nearest medical institute, smoking, drinking, and exercise. Nonlinear relationship between altitudes and prevalence of hypertension was explored by restricted cubic spline analyses. Sensitivity analyses were conducted by restricting to residents of rural and/or nomadic areas. The prevalence of hypertension was estimated to be 37.6%. We found a U-shaped association between altitudes and prevalence of physician-diagnosed hypertension with a turning point at around 3800 m (12,467 ft). For residents living above 3800 m, a 1000 m increase in altitudes was associated with 2.05 (95% confidence interval [CI]: 1.62-2.61) times higher odds of having physician-diagnosed hypertension, after adjusting for age and gender. When further controlling for all covariates, the odds ratio (OR) dropped to 1.87 (95% CI: 1.46-2.41). For residents living below 3800 m, a 1000 m increase was associated with 0.29 (95% CI: 0.19-0.44) times less likelihood of having physician-diagnosed hypertension in the full model. Sensitivity analyses among residents in rural and/or nomadic areas showed similar associations. To conclude, altitudes were in a U-shaped association with prevalence of hypertension.

Reconstructing 1D Fe Single-atom Catalytic Structure on 2D Graphene Film for High-Efficiency Oxygen Reduction Reaction.

The ordinary intrinsic activity and disordered distribution of metal sites in zero/one-dimensional (0D/1D) single-atom catalysts (SACs) lead to inferior catalytic efficiency and short-term endurance in the oxygen reduction reaction (ORR), which restricts the large-scale application of hydrogen-oxygen fuel cells and metal-air batteries. To improve the activity of SACs, a mild synthesis method was chosen to conjugate 1D Fe SACs with 2D graphene film (Fe SAC@G) that realized a composite structure with well-ordered atomic-Fe coordination configuration. The product exhibits outstanding ORR electrocatalytic efficiency and stability in 0.1 M KOH aqueous solution. DFT-D computational results manifest the intrinsic ORR activity of Fe SAC@G originated from the newly-formed FeN4 -O-FeN4 bridge structure with moderate adsorption ability towards ORR intermediates. These findings provide new ways for designing SACs with high activity and long-term stability.

Community Outbreak Investigation of SARS-CoV-2 Transmission Among Bus Riders in Eastern China.

Importance: Evidence of whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be transmitted as an aerosol (ie, airborne) has substantial public health implications. Objective: To investigate potential transmission routes of SARS-CoV-2 infection with epidemiologic evidence from a COVID-19 outbreak. Design, Setting, and Participants: This cohort study examined a community COVID-19 outbreak in Zhejiang province. On January 19, 2020, 128 individuals took 2 buses (60 [46.9%] from bus 1 and 68 [53.1%] from bus 2) on a 100-minute round trip to attend a 150-minute worship event. The source patient was a passenger on bus 2. We compared risks of SARS-CoV-2 infection among at-risk individuals taking bus 1 (n = 60) and bus 2 (n = 67 [source patient excluded]) and among all other individuals (n = 172) attending the worship event. We also divided seats on the exposed bus into high-risk and low-risk zones according to the distance from the source patient and compared COVID-19 risks in each zone. In both buses, central air conditioners were in indoor recirculation mode. Main Outcomes and Measures: SARS-CoV-2 infection was confirmed by reverse transcription polymerase chain reaction or by viral genome sequencing results. Attack rates for SARS-CoV-2 infection were calculated for different groups, and the spatial distribution of individuals who developed infection on bus 2 was obtained. Results: Of the 128 participants, 15 (11.7%) were men, 113 (88.3%) were women, and the mean age was 58.6 years. On bus 2, 24 of the 68 individuals (35.3% [including the index patient]) received a diagnosis of COVID-19 after the event. Meanwhile, none of the 60 individuals in bus 1 were infected. Among the other 172 individuals at the worship event, 7 (4.1%) subsequently received a COVID-19 diagnosis. Individuals in bus 2 had a 34.3% (95% CI, 24.1%-46.3%) higher risk of getting COVID-19 compared with those in bus 1 and were 11.4 (95% CI, 5.1-25.4) times more likely to have COVID-19 compared with all other individuals attending the worship event. Within bus 2, individuals in high-risk zones had moderately, but nonsignificantly, higher risk for COVID-19 compared with those in the low-risk zones. The absence of a significantly increased risk in the part of the bus closer to the index case suggested that airborne spread of the virus may at least partially explain the markedly high attack rate observed. Conclusions and Relevance: In this cohort study and case investigation of a community outbreak of COVID-19 in Zhejiang province, individuals who rode a bus to a worship event with a patient with COVID-19 had a higher risk of SARS-CoV-2 infection than individuals who rode another bus to the same event. Airborne spread of SARS-CoV-2 seems likely to have contributed to the high attack rate in the exposed bus. Future efforts at prevention and control must consider the potential for airborne spread of the virus.

Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: a nationally representative cohort study.

BACKGROUND: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. METHODS: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. RESULTS: Among 8204 participants aged 50-75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: "persistently low trajectory" (n = 1550, 18.9%), "persistently moderate trajectory" (n = 3194, 38.9%), and "persistently high trajectory" (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38-0.77) and social activities (OR 0.79, 95% CI 0.65-0.95) were both associated with a lower likelihood of being in the "persistently low trajectory" for global cognitive function. CONCLUSIONS: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.

Association of Low to Moderate Alcohol Drinking With Cognitive Functions From Middle to Older Age Among US Adults.

Importance: Studies examining the association of low to moderate drinking with various cognitive functions have yielded mixed findings. Objective: To investigate whether associations exist between low to moderate alcohol drinking and cognitive function trajectories or rates of change in cognitive function from middle age to older age among US adults. Design, Setting, and Participants: A prospective cohort study of participants drawn from the Health and Retirement Study (HRS), a nationally representative sample of US adults, with mean (SD) follow-up of 9.1 (3.1) years. In total, 19 887 participants who had their cognitive functions measured in the HRS starting in 1996 through 2008 and who had participated in at least 3 biennial surveys were included. The data analysis was conducted from June to November 2019. Exposures: Alcohol consumption and aging. Main Outcomes and Measures: Trajectories and annual rates of change for the cognitive domains of mental status, word recall, and vocabulary and for the total cognitive score, which was the sum of the mental status and word recall scores. Participants were clustered into 2 cognitive function trajectories for each cognition measure assessed based on their scores at baseline and through at least 3 biennial surveys: a consistently low trajectory (representing low cognitive scores throughout the study period) and a consistently high trajectory (representing high cognitive scores throughout the study period). Results: The mean (SD) age of 19 887 participants was 61.8 (10.2) years, and the majority of the HRS participants were women (11 943 [60.1%]) and of white race/ethnicity (16 950 [85.2%]). Low to moderate drinking (<8 drinks per week for women and <15 drinks per week for men) was significantly associated with a consistently high cognitive function trajectory and a lower rate of cognitive decline. Compared with never drinkers, low to moderate drinkers were less likely to have a consistently low trajectory for total cognitive function (odds ratio [OR], 0.66; 95% CI, 0.59-0.74), mental status (OR, 0.71; 95% CI, 0.63-0.81), word recall (OR, 0.74; 95% CI, 0.69-0.80), and vocabulary (OR, 0.64; 95% CI, 0.56-0.74) (all P < .001). In addition, low to moderate drinking was associated with decreased annual rates of total cognitive function decline (ß coefficient, 0.04; 95% CI, 0.02-0.07; P = .002), mental status (ß coefficient, 0.02; 95% CI, 0.01-0.03; P = .002), word recall (ß coefficient, 0.02; 95% CI, 0.01-0.04; P = .01), and vocabulary (ß coefficient, 0.01; 95% CI, 0.00-0.03; P = .08). A significant racial/ethnic difference was observed for trajectories of mental status (P = .02 for interaction), in which low to moderate drinking was associated with lower odds of having a consistently low trajectory for white participants (OR, 0.65; 95% CI, 0.56-0.75) but not for black participants (OR, 1.02; 95% CI, 0.74-1.39). Finally, the dosage of alcohol consumed had a U-shaped association with all cognitive function domains for all participants, with an optimal dose of 10 to 14 drinks per week. Conclusions and relevance: These findings suggested that low to moderate alcohol drinking was associated with better global cognition scores, and these associations appeared stronger for white participants than for black participants. Studies examining the mechanisms underlying the association between alcohol drinking and cognition in middle-aged or older adults are needed.

The effect of leptin on blood pressure considering smoking status: a Mendelian randomization study.

Studies on leptin and blood pressure (BP) associations have yielded inconsistent findings. The current study aimed to evaluate the effect of genetically determined leptin on BP and to explore whether smoking status modified this effect. We conducted a Mendelian randomization analysis using the baseline data of 3860 participants in the Framingham Heart Study 3rd generation cohort. Pairwise associations among leptin genetic risk score (GRS), log-transformed leptin (log-leptin), and BP were assessed by multivariate linear regression models. Age and sex were adjusted in the base model, and education, smoking, drinking, and physical activity were adjusted in the full model. The interaction between leptin GRS and smoking was evaluated by adding an interaction term, GRS × smoking, in the fully adjusted model. In the age- and sex-adjusted analyses, log-leptin was positively associated with systolic BP (SBP) (P = 2.35 × 10-79), diastolic BP (DBP) (P = 6.19 × 10-76), mean arterial pressure (MAP) (P = 1.10 × 10-90), and pulse pressure (P = 4.38 × 10-19). Leptin GRS significantly increased log-leptin (P = 0.00001). Leptin GRS was associated with reduced SBP (P = 0.04), DBP (P = 0.006), and MAP (P = 0.008) among current smokers. In the fully adjusted model, significant interactions between GRS and smoking were identified for SBP (P = 0.02), DBP (P = 0.002), and MAP (P = 0.003). Sensitivity analyses among participants not taking antihypertensive or glucose-lowering medications revealed similar associations. Our study provided evidence for a potentially causal relationship between leptin and BP among current smokers.

Insights into the ecological roles and evolution of methyl-coenzyme M reductase-containing hot spring Archaea.

Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor.