Redundant neural circuits regulate olfactory integration.

Olfactory integration is important for survival in a natural habitat. However, how the nervous system processes signals of two odorants present simultaneously to generate a coherent behavioral response is poorly understood. Here, we characterize circuit basis for a form of olfactory integration in Caenorhabditis elegans. We find that the presence of a repulsive odorant, 2-nonanone, that signals threat strongly blocks the attraction of other odorants, such as isoamyl alcohol (IAA) or benzaldehyde, that signal food. Using a forward genetic screen, we found that genes known to regulate the structure and function of sensory neurons, osm-5 and osm-1, played a critical role in the integration process. Loss of these genes mildly reduces the response to the repellent 2-nonanone and disrupts the integration effect. Restoring the function of OSM-5 in either AWB or ASH, two sensory neurons known to mediate 2-nonanone-evoked avoidance, is sufficient to rescue. Sensory neurons AWB and downstream interneurons AVA, AIB, RIM that play critical roles in olfactory sensorimotor response are able to process signals generated by 2-nonanone or IAA or the mixture of the two odorants and contribute to the integration. Thus, our results identify redundant neural circuits that regulate the robust effect of a repulsive odorant to block responses to attractive odorants and uncover the neuronal and cellular basis for this complex olfactory task.

The Association of Hypertension with Perfluoroalkyl and Polyfluoroalkyl Substances.

Perfluoroalkyl and polyfluoroalkyl substance (PFAS) is a large group of fluorinated synthetic chemicals, e.g., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), and perfluorononanoic acid (PFNA). Many epidemiological studies have found that PFAS exposure is associated with hypertension risk, but others possess a different opinion. Overall, the relationship between PFASs and hypertension risk remains controversial. We sought to conduct a systematic review and meta-analysis to clarify the association between PFAS exposure and human risk of hypertension.We conducted a meta-analysis based on population-involving studies published from 1975 to 2023, which we collected from Web of Science, PubMed, and Embase databases. The odds ratio (OR) and standardized mean difference (SMD), with their 95% confidence interval (CI), were used to assess the risk of hypertension with PFAS exposure. The statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Research publications related to our meta-analysis topic were systematically reviewed.Fourteen studies involving 71,663 participants, in which 26,281 suffered hypertension, met the inclusion criteria. Our analyses suggest that exposure to general PFAS (OR = 1.09, 95% CI = 1.04-1.14) or PFOS (OR = 1.17, 95% CI = 1.05-1.30) is associated with hypertension risk. Specifically, elevated levels of general PFAS (SMD = 0.25, 95% CI = 0.08-0.42), PFHxS (SMD = 0.17, 95% CI = 0.07-0.27), and PFDA (SMD = 0.08, 95% CI = 0.02-0.13) are associated with a high risk of hypertension.Our meta-analysis indicates that PFAS exposure is a risk factor for hypertension, and increased hypertension risk is associated with higher PFAS levels. Further study may eventually provide a better and more comprehensive elucidation of the potential mechanism of this association.

Association between brominated flame retardants and risk of endocrine-related cancer: A systematic review and meta-analysis.

BACKGROUND: The incidence of endocrine-related cancer, which includes tumors in major endocrine glands such as the breast, thyroid, pituitary, and prostate, has been increasing year by year. Various studies have indicated that brominated flame retardants (BFRs) are neurotoxic, endocrine-toxic, reproductive-toxic, and even carcinogenic. However, the epidemiological relationship between BFR exposure and endocrine-related cancer risk remains unclear. METHODS: We searched the PubMed, Google Scholar, and Web of Science databases for articles evaluating the association between BFR exposure and endocrine-related cancer risk. The odds ratio (OR) and its corresponding 95% confidence interval (95% CI) were used to assess the association. Statistical heterogeneity among studies was assessed with the Q-test and I2 statistics. Begg's test was performed to evaluate the publication bias. RESULTS: We collected 15 studies, including 6 nested case-control and 9 case-control studies, with 3468 cases and 4187 controls. These studies assessed the risk of breast cancer, thyroid cancer, and endocrine-related cancers in relation to BFR levels. Our findings indicate a significant association between BFR exposure in adipose tissue and an increased risk of breast cancer. However, this association was not observed for thyroid cancer. Generally, BFR exposure appears to elevate the risk of endocrine-related cancers, with a notable increase in risk linked to higher levels of BDE-28, a specific polybrominated diphenyl ether congener. CONCLUSIONS: In conclusion, although this meta-analysis has several limitations, our results suggest that BFR exposure is a significant risk factor for breast cancer, and low-brominated BDE-28 exposure could significantly increase the risk of endocrine-related cancers. Further research is essential to clarify the potential causal relationships between BFRs and endocrine-related cancers, and their carcinogenic mechanisms.

Association between metal(loid)s in serum and leukemia: a systematic review and meta-analysis.

Purpose: Heavy metals and metalloids are recognized as environmental threats, which are considered highly toxic and carcinogenic. Epidemiologically, their association with leukemia is under debate. We aim to clarify the association between the heavy metal(loid)s in serum and leukemia via a systematic review and meta-analysis. Methods: We searched PubMed, Embase, Google Scholar, and CNKI (China National Knowledge Infrastructure) databases for all related articles. The standardized mean difference and its 95% confidence interval was used to evaluate the association of leukemia with heavy metal(loid)s in serum. The statistical heterogeneity among studies was assessed with the Q-test and I 2 statistics. Results: Among 4,119 articles related to metal(loid)s and leukemia, 21 studies met our inclusion criteria, which are all cross-sectional studies. These 21 studies involved 1,316 cases and 1,310 controls, based on which we evaluate the association of heavy metals/metalloids in serum with leukemia. Our results indicated positive differences for serum chromium, nickel, and mercury in leukemia patients, while a negative difference for serum manganese in acute lymphocytic leukemia (ALL). Conclusion: Our results suggested an elevated trend of serum chromium, nickel, and mercury concentrations in leukemia patients while descending trend of serum manganese concentration in ALL patients. The result of sensitivity analysis between lead, cadmium, and leukemia and publication bias of association between chromium and leukemia also needed attention. Future research work may focus on the dose-response relationship between any of these elements and the leukemia risks, and further elucidation of how these elements are related to leukemia may shed light on the prevention and treatment of leukemia. Supplementary Information: The online version contains supplementary material available at 10.1007/s40201-023-00853-2.

A new miniMOS tool kit capable of visualizing single copy insertion in C. elegans.

The miniMOS technique has been widely used in the C. elegans community to generate single copy insertions. A worm is considered as a potential insertion candidate if it is resistant to G418 antibiotics and does not express a co-injected fluorescence marker. If the expression of the extrachromosomal array is very low, it is possible for a worm to be mistakenly identified as a miniMOS candidate, as this low expression level can still confer resistance to G418 without producing a detectable fluorescence signal from the co-injection marker. This may increase the workload for identifying the insertion locus in the subsequent steps. In the present study, we modified the plasmid platform for miniMOS insertion by incorporating a myo-2 promoter-driven TagRFP or a ubiquitous H2B::GFP expression cassette into the targeting vector and introducing two loxP sites flanking the selection cassettes. Based on this new miniMOS tool kit, the removable fluorescence reporters can be used to visualize the single copy insertions, greatly reducing insertion locus identification efforts. In our experience, this new platform greatly facilitates the isolation of the miniMOS mutants.

Crystal structure of poly[(4-amino-pyridine-κN)(N,N-di-methyl-formamide-κO)(µ3-pyridine-3,5-di-carboxyl-ato-κ(3) N:O (3):O (5))copper(II)].

The title compound, [Cu(C7H3NO4)(C5H6N2)(C3H7NO] n , is an amino-function-alized chiral metal-organic framework with (10,3)-a topology. It has been constructed via the assembly of the achiral triconnected pyridine-3,5-di-carboxyl-ate (3,5-PDC) building block and a triconnected Cu(II) atom. Each Cu(II) ion is coordinated by two O atoms and one N atom, respectively, of three crystallographically independent 3,5-PDC ligands. The square-pyramidal (CuN2O3) coordination geometry of the Cu(II) ion is completed by an N atom of a terminal 4-amino-pyridine (4-APY) ligand and the O atom of a terminal N,N-di-methyl-formamide (DMF) ligand to give a triconnected 'T'-shaped secondary building unit, which becomes trigonal in the resulting (10,3)-a topology. In the three-dimensional structure, weak N-H⋯O hydrogen bonds are observed in which the donor N-H groups are provided by the 4-APY ligands and the acceptor O atoms are provided by the non-coordinating carboxylate O atoms of the 3,5-PDC ligands.