Mitochondria-localized lncRNA HITT inhibits fusion by attenuating formation of mitofusin-2 homotypic or heterotypic complexes.

Long noncoding RNAs (lncRNAs) are emerging as essential players in multiple biological processes. Mitochondrial dynamics, comprising the continuous cycle of fission and fusion, are required for healthy mitochondria that function properly. Despite long-term recognition of its significance in cell-fate control, the mechanism underlying mitochondrial fusion is not completely understood, particularly regarding the involvement of lncRNAs. Here, we show that the lncRNA HITT (HIF-1α inhibitor at translation level) can specifically localize in mitochondria. Cells expressing higher levels of HITT contain fragmented mitochondria. Conversely, we show that HITT knockdown cells have more tubular mitochondria than is present in control cells. Mechanistically, we demonstrate HITT directly binds mitofusin-2 (MFN2), a core component that mediates mitochondrial outer membrane fusion, by the in vitro RNA pull-down and UV-cross-linking RNA-IP assays. In doing so, we found HITT disturbs MFN2 homotypic or heterotypic complex formation, attenuating mitochondrial fusion. Under stress conditions, such as ultraviolet radiation, we in addition show HITT stability increases as a consequence of MiR-205 downregulation, inhibiting MFN2-mediated fusion and leading to apoptosis. Overall, our data provide significant insights into the roles of organelle (mitochondria)-specific resident lncRNAs in regulating mitochondrial fusion and also reveal how such a mechanism controls cellular sensitivity to UV radiation-induced apoptosis.

Characteristic of water quality indicators and its response to climate conditions in the middle and lower reaches of Lijiang River, China.

With global climate change and increasingly extreme weather conditions, the water quality of the Lijiang River Basin (LRB) is facing huge threats. At present, there is still a lack of systematic research on water quality indicators and the influence of indirect factors such as meteorological factors on it in the LRB. Therefore, this study is based on the meteorological, hydrological, and water quality data of the LRB from 2012 to 2018, using the Mann-Kendall test, Morlet wavelet method, Spearman's rank correlation coefficient, sensitivity, and contribution rate to quantitative analysis of the relationship between climate conditions and water quality indicators. The results show that the change trends of these hydrological and climatic conditions have almost no significant sudden change; precipitation and streamflow are decreasing each year; the streamflow trend exhibits time hysteresis; precipitation has a stronger influence downstream than on the local area; water quality indicators of both stations exhibited a change period of around 18 to 20 months, with the exception of pH. Water quality indicators are insensitive to precipitation and streamflow, and sensitive to humidity and wind speed; DO was negatively correlated with climate indicators apart from wind speed; almost all water quality indicators in Yangshuo are highly sensitive to air temperature, and the contribution rate of air temperature to ORP and TP reached 4.81% and 3.56%, respectively; sunshine duration has a positive impact on reducing NH4-N and TP. The difference between Yangshuo and Guilin is mostly due to the input of external sources on both sides of the Lijiang River, which results in variations in climate conditions sensitivities.

Occurrence, source tracking and removal of antibiotics in recirculating aquaculture systems (RAS) in southern China.

The recirculating aquaculture system (RAS) has attracted much attention in China as a way to rapidly transform and upgrade aquaculture ponds to realize zero-emissions of pollutants in aquaculture tail water. Tail water purification ponds (TWPPs) play an important role in the treatment of aquaculture wastewater. However, until now, there have been few reports on the occurrence of antibiotics in RAS and the removal of antibiotics from the TWPPs of RAS. Therefore, this study focused on the occurrence of antibiotics in a typical ecological RAS. For comparison, the same measurements were simultaneously carried out in nearby open aquaculture ponds and rivers. The pollution level and spatial distribution of antibiotics in the RAS and the removal of antibiotics in the TWPPs were explored. The results showed that (1) eleven and twelve antibiotics were detected in water and sediment samples in the RAS, respectively, but no antibiotics were found in fish muscles and feed. Erythromycin (ERY), lincomycin (LIN), and ciprofloxacin (CFX) were the three main types of antibiotics found in water and sediment samples. (2) The TWPPs of the RAS can effectively remove antibiotics in aquaculture water. The antibiotic concentration in recirculating aquaculture ponds of the RAS was as high as 180 ng/L. After treatments in the TWPPs, the antibiotic concentration of aquaculture water decreased to 81.6 ng/L (3) The antibiotic concentrations in recirculating aquaculture ponds (25.2-180 ng/L) were lower than those in the nearby open aquaculture ponds (126-267.3 ng/L), and the concentration of antibiotics in the sediments of recirculating aquaculture ponds was up to 22.9 ng/g, while that in TWPPs was as high as 56.1 ng/g. In conclusion, the antibiotic residues in the RAS were low after antibiotics were banned in feed in China, and the removal of antibiotics in the TWPPs was more pronounced. Furthermore, cross-contamination was found between the RAS, surrounding open aquaculture ponds and the river, and the water supply of the RAS was likely to be the main contributor of antibiotics in the aquaculture environments. This study can help the government formulate discharge standards for antibiotics in aquaculture and also provide a reference for the transformation and upgrading of aquaculture ponds to achieve a zero-emission aquaculture mode.

A newly recorded Rickettsia of the Torix group is a recent intruder and an endosymbiont in the whitefly Bemisia tabaci.

The bacterium Rickettsia is found widely in phytophagous insects and often exerts profound effects on the phenotype and fitness of its hosts. Here, we decrypt a new, independent, phylogenetically ancient Torix Rickettsia endosymbiont found constantly in a laboratory line of an economically important insect Asia II 7, a putative species of the Bemisia tabaci whitefly complex (Hemiptera: Aleyrodidae), and occasionally in field whitefly populations. This new Rickettsia distributes throughout the body of its whitefly host. Genetically, compared to Rickettsia_bellii_MEAM1 found earlier in whiteflies, the new Rickettsia species has more gene families and pathways, which may be important factors in shaping specific symbiotic relationships. We propose the name 'Candidatus Rickettsia_Torix_Bemisia_tabaci (RiTBt)' for this new endosymbiont associated with whiteflies. Comparative genomic analyses indicate that RiTBi may be a relatively recent intruder in whiteflies given its low abundance in the field and relatively larger genome compared to Rickettsia_bellii_MEAM1.

Effect of intermittent aeration mode on nitrogen concentration in the water column and sediment pore water of aquaculture ponds.

Nitrogen in pond sediments is a major water quality concern and can impact the productivity of aquaculture. Dissolved oxygen is an important factor for improving water quality and boosting fish growth in aquaculture ponds, and plays an important role in the conversion of ammonium-nitrogen (NH4+-N) to nitrite-nitrogen (NO2--N) and eventually nitrate-nitrogen (NO3--N). A central goal of the study was to identify the best aeration method and strategy for improving water quality in aquaculture ponds. We conducted an experiment with six tanks, each with a different aeration mode to simulate the behavior of aquaculture ponds. The results show that a 36 hr aeration interval (Tc = 36 hr: 36 hr) and no aeration resulted in high concentrations of NH4+-N in the water column. Using a 12 hr interval time (Tc = 12 hr: 12 hr) resulted in higher NO2--N and NO3--N concentrations than any other aeration mode. Results from an 8 hr interval time (Tc = 8 hr: 8 hr) and 24 hr interval time (Tc = 24 hr: 24 hr) were comparable with those of continuous aeration, and had the benefit of being in use for only half of the time, consequently reducing energy consumption.

Behavioral response inhibition and maturation of goal representation in prefrontal cortex after puberty.

Executive functions including behavioral response inhibition mature after puberty, in tandem with structural changes in the prefrontal cortex. Little is known about how activity of prefrontal neurons relates to this profound cognitive development. To examine this, we tracked neuronal responses of the prefrontal cortex in monkeys as they transitioned from puberty into adulthood and compared activity at different developmental stages. Performance of the antisaccade task greatly improved in this period. Among neural mechanisms that could facilitate it, reduction of stimulus-driven activity, increased saccadic activity, or enhanced representation of the opposing goal location, only the latter was evident in adulthood. Greatly accentuated in adults, this neural correlate of vector inversion may be a prerequisite to the formation of a motor plan to look away from the stimulus. Our results suggest that the prefrontal mechanisms that underlie mature performance on the antisaccade task are more strongly associated with forming an alternative plan of action than with suppressing the neural impact of the prepotent stimulus.

Distinct Mechanism for the Formation of the Ribonucleoprotein Complex of Tomato Spotted Wilt Virus.

The Tomato spotted wilt virus (TSWV) belongs to the Tospovirus genus of the Bunyaviridae family and represents the sole plant-infecting group within bunyavirus. TSWV encodes a nucleocapsid protein (N) which encapsidates the RNA genome to form a ribonucleoprotein complex (RNP). In addition, the N has multiple roles during the infection of plant cells. Here, we report the crystal structure of the full-length TSWV N. The N features a body domain consisting of an N-lobe and a C-lobe. These lobes clamp a positively charged groove which may constitute the RNA binding site. Furthermore, the body domains are flanked by N- and C-terminal arms which mediate homotypic interactions to the neighboring subunits, resulting in a ring-shaped N trimer. Interestingly, the C terminus of one protomer forms an additional interaction with the protomer of an adjacent trimer in the crystal, which may constitute a higher-order oligomerization contact. In this way, this study provides insights into the structure and trimeric assembly of TSWV N, which help to explain previous functional findings, but also suggests distinct N interactions within a higher-order RNP.IMPORTANCE TSWV is one of the most devastating plant pathogens that cause severe diseases in numerous agronomic and ornamental crops worldwide. TSWV is also the prototypic member of the Tospovirus genus, which is the sole group of plant-infecting viruses in the bunyavirus family. This study determined the structure of full-length TSWV N in an oligomeric state. The structural observations explain previously identified biological properties of TSWV N. Most importantly, the additional homotypic interaction between the C terminus of one protomer with another protomer indicates that there is a distinct mechanism of RNP formation in the bunyavirus family, thereby enhancing the current knowledge of negative-sense single-stranded RNA virus-encoded N. TSWV N is the last remaining representative N with an unknown structure in the bunyavirus family. Combined with previous studies, the structure of TSWV N helps to build a complete picture of the bunyavirus-encoded N family and reveals a close evolutionary relationship between orthobunyavirus, phlebovirus, hantavirus, and tospovirus.

Age-dependent changes in prefrontal intrinsic connectivity.

The prefrontal cortex continues to mature after puberty and into early adulthood, mirroring the time course of maturation of cognitive abilities. However, the way in which prefrontal activity changes during peri- and postpubertal cortical maturation is largely unknown. To address this question, we evaluated the developmental stage of peripubertal rhesus monkeys with a series of morphometric, hormonal, and radiographic measures, and conducted behavioral and neurophysiological tests as the monkeys performed working memory tasks. We compared firing rate and the strength of intrinsic functional connectivity between neurons in peripubertal vs. adult monkeys. Notably, analyses of spike train cross-correlations demonstrated that the average magnitude of functional connections measured between neurons was lower overall in the prefrontal cortex of peripubertal monkeys compared with adults. The difference resulted because negative functional connections (indicative of inhibitory interactions) were stronger and more prevalent in peripubertal compared with adult monkeys, whereas the positive connections showed similar distributions in the two groups. Our results identify changes in the intrinsic connectivity of prefrontal neurons, particularly that mediated by inhibition, as a possible substrate for peri- and postpubertal advances in cognitive capacity.

Task dependence of decision- and choice-related activity in monkey oculomotor thalamus.

Oculomotor signals circulate within putative recurrent feedback loops that include the frontal eye field (FEF) and the oculomotor thalamus (OcTh). To examine how OcTh contributes to visuomotor control, and perceptually informed saccadic choices in particular, neural correlates of perceptual judgment and motor selection in OcTh were evaluated and compared with those previously reported for FEF in the same subjects. Monkeys performed three tasks: a choice task in which perceptual decisions are urgent, a choice task in which identical decisions are made without time pressure, and a single-target, delayed saccade task. The OcTh yielded far fewer task-responsive neurons than the FEF, but across responsive pools, similar neuron types were found, ranging from purely visual to purely saccade related. Across such types, the impact of the perceptual information relevant to saccadic choices was qualitatively the same in FEF and OcTh. However, distinct from that in FEF, activity in OcTh was strongly task dependent, typically being most vigorous in the urgent task, less so in the easier choice task, and least in the single-target task. This was true for responsive and nonresponsive cells alike. Neurons with exclusively motor-related activity showed strong task dependence, fired less, and differed most patently from their FEF counterparts, whereas those that combined visual and motor activity fired most similarly to their FEF counterparts. The results suggest that OcTh activity is more distantly related to saccade production per se, because its degree of commitment to a motor choice varies markedly as a function of ongoing cognitive or behavioral demands.

Genome reduction and potential metabolic complementation of the dual endosymbionts in the whitefly Bemisia tabaci.

BACKGROUND: The whitefly Bemisia tabaci is an important agricultural pest with global distribution. This phloem-sap feeder harbors a primary symbiont, "Candidatus Portiera aleyrodidarum", which compensates for the deficient nutritional composition of its food sources, and a variety of secondary symbionts. Interestingly, all of these secondary symbionts are found in co-localization with the primary symbiont within the same bacteriocytes, which should favor the evolution of strong interactions between symbionts. RESULTS: In this paper, we analyzed the genome sequences of the primary symbiont Portiera and of the secondary symbiont Hamiltonella in the B. tabaci Mediterranean (MED) species in order to gain insight into the metabolic role of each symbiont in the biology of their host. The genome sequences of the uncultured symbionts Portiera and Hamiltonella were obtained from one single bacteriocyte of MED B. tabaci. As already reported, the genome of Portiera is highly reduced (357 kb), but has kept a number of genes encoding most essential amino-acids and carotenoids. On the other hand, Portiera lacks almost all the genes involved in the synthesis of vitamins and cofactors. Moreover, some pathways are incomplete, notably those involved in the synthesis of some essential amino-acids. Interestingly, the genome of Hamiltonella revealed that this secondary symbiont can not only provide vitamins and cofactors, but also complete the missing steps of some of the pathways of Portiera. In addition, some critical amino-acid biosynthetic genes are missing in the two symbiotic genomes, but analysis of whitefly transcriptome suggests that the missing steps may be performed by the whitefly itself or its microbiota. CONCLUSIONS: These data suggest that Portiera and Hamiltonella are not only complementary but could also be mutually dependent to provide a full complement of nutrients to their host. Altogether, these results illustrate how functional redundancies can lead to gene losses in the genomes of the different symbiotic partners, reinforcing their inter-dependency.

Core-binding factor subunit beta is not required for non-primate lentiviral Vif-mediated APOBEC3 degradation.

Viral infectivity factor (Vif) is required for lentivirus fitness and pathogenicity, except in equine infectious anemia virus (EIAV). Vif enhances viral infectivity by a Cullin5-Elongin B/C E3 complex to inactivate the host restriction factor APOBEC3. Core-binding factor subunit beta (CBF-ß) is a cell factor that was recently shown to be important for the primate lentiviral Vif function. Non-primate lentiviral Vif also degrades APOBEC3 through the proteasome pathway. However, it is unclear whether CBF-ß is required for the non-primate lentiviral Vif function. In this study, we demonstrated that the Vifs of non-primate lentiviruses, including feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), caprine arthritis encephalitis virus (CAEV), and maedi-visna virus (MVV), do not interact with CBF-ß. In addition, CBF-ß did not promote the stability of FIV, BIV, CAEV, and MVV Vifs. Furthermore, CBF-ß silencing or overexpression did not affect non-primate lentiviral Vif-mediated APOBEC3 degradation. Our results suggest that non-primate lentiviral Vif induces APOBEC3 degradation through a different mechanism than primate lentiviral Vif. Importance: The APOBEC3 protein family members are host restriction factors that block retrovirus replication. Vif, an accessory protein of lentivirus, degrades APOBEC3 to rescue viral infectivity by forming Cullin5-Elongin B/C-based E3 complex. CBF-ß was proved to be a novel regulator of primate lentiviral Vif function. In this study, we found that CBF-ß knockdown or overexpression did not affect FIV Vif's function, which induced polyubiquitination and degradation of APOBEC3 by recruiting the E3 complex in a manner similar to that of HIV-1 Vif. We also showed that other non-primate lentiviral Vifs did not require CBF-ß to degrade APOBEC3. CBF-ß did not interact with non-primate lentiviral Vifs or promote their stability. These results suggest that a different mechanism exists for the Vif-APOBEC interaction and that non-primates are not suitable animal models for exploring pharmacological interventions that disrupt Vif-CBF-ß interaction.

Perceptual modulation of motor--but not visual--responses in the frontal eye field during an urgent-decision task.

Neuronal activity in the frontal eye field (FEF) ranges from purely motor (related to saccade production) to purely visual (related to stimulus presence). According to numerous studies, visual responses correlate strongly with early perceptual analysis of the visual scene, including the deployment of spatial attention, whereas motor responses do not. Thus, functionally, the consensus is that visually responsive FEF neurons select a target among visible objects, whereas motor-related neurons plan specific eye movements based on such earlier target selection. However, these conclusions are based on behavioral tasks that themselves promote a serial arrangement of perceptual analysis followed by motor planning. So, is the presumed functional hierarchy in FEF an intrinsic property of its circuitry or does it reflect just one possible mode of operation? We investigate this in monkeys performing a rapid-choice task in which, crucially, motor planning always starts ahead of task-critical perceptual analysis, and the two relevant spatial locations are equally informative and equally likely to be target or distracter. We find that the choice is instantiated in FEF as a competition between oculomotor plans, in agreement with model predictions. Notably, although perception strongly influences the motor neurons, it has little if any measurable impact on the visual cells; more generally, the more dominant the visual response, the weaker the perceptual modulation. The results indicate that, contrary to expectations, during rapid saccadic choices perceptual information may directly modulate ongoing saccadic plans, and this process is not contingent on prior selection of the saccadic goal by visually driven FEF responses.

Investigation of the molecular mechanism of Danggui Buxue tang in treating lung cancer using network pharmacology and molecular docking techniques.

This study used network pharmacology and molecular docking techniques to investigate the molecular targets and pathways of Danggui Buxue Tang (DBT) in treating lung cancer. The compound-target network was constructed using the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), and a lung cancer-specific network was created using the GEO database and Cytoscape software. GO and KEGG pathway analyses were performed to understand the biological processes associated with DBT. The key compounds from Astragalus, kaempferol, and quercetin, and the potential targets are IL-6, IL-1ß, FOS, ICAM1, and CCL2. GO enrichment analysis revealed numerous biological process-related entries, while KEGG pathway analysis highlighted the TNF and IL-17 signalling pathways. Molecular docking confirmed the stable binding activity between the main active compounds of DBT and the target proteins. Overall, these findings shed light on the molecular mechanism of DBT in treating lung cancer, providing insights into targets, pathways, and biological processes involved.

Cross-contamination and ecological risk assessment of antibiotics between rivers and surrounding open aquaculture ponds.

Antibiotics are causing widespread concern as one of the emerging contaminants. There is the abuse of antibiotics in high-density open aquaculture, and the tailwater is often discharged into surrounding rivers. At the same time, the water replenishment of open aquaculture ponds from nearby rivers containing antibiotic contamination from different sources may result in cross-contamination. However, it is still unclear which pollution intensity is greater in rivers or in open aquaculture. So in this paper, the levels of 20 antibiotics (i.e., Fluoroquinolones (FQs), Sulfonamides (SAs), Tetracyclines (TCs), Macrolides (MLs) and Lincosamides (LCs)) in rivers and high-density open aquaculture ponds were investigated in the Baini River basin in the suburbs of Guangzhou, China. The results showed that norfloxacin (NFX) was the predominant antibiotic in river and aquaculture water, with concentrations ranging from 6.12 to 156.04 ng/L and from 7.47 to 82.62 ng/L in both aquatic systems, respectively. As for the pollution intensity of antibiotics, the annual pollution contribution (28.64 kg/a) of the river water supply to open aquaculture is higher than that (10.81 kg/a) of open aquaculture to the river, which means river pollution has a greater impact on aquaculture ponds. The risk quotient (RQ) showed that the ecological risk of lincomycin (LIN), erythromycin (ERY), sulfamethoxazole (SMX), norfloxacin (NFX), ciprofloxacin (CFX) and chlortetracycline (CTC) in rivers and aquaculture environments had high ecological risks from 1.21 to 1.81. Water interactions with contaminated rivers will result in a corresponding increase in the ecological risk of antibiotics in the aquaculture environment. Overall, according to the results, the risk of polluted rivers to open aquaculture cannot be ignored, and it is recommended that open aquaculture should use these water sources with caution, and that the water quality evaluation of aquaculture water should be increased with monitoring indicators for emerging contaminants such as antibiotics.

Unveiling the power of COD/N on constructed wetlands in a short-term experiment: Exploring microbiota co-occurrence patterns and assembly dynamics.

Constructed wetlands (CWs) are a cost-effective and environmentally friendly wastewater treatment technology. The influent chemical oxygen demand (COD)/nitrogen (N) ratio (CNR) plays a crucial role in microbial activity and purification performance. However, the effects of CNR changes on microbial diversity, interactions, and assembly processes in CWs are not well understood. In this study, we conducted comprehensive mechanistic experiments to investigate the response of CWs to changes in influent CNR, focusing on the effluent, rhizosphere, and substrate microbiota. Our goal is to provide new insights into CW management by integrating microbial ecology and environmental engineering perspectives. We constructed two groups of horizontal subsurface flow constructed wetlands (HFCWs) and set up three influent CNRs to analyse the microbial responses and nutrient removal. The results indicated that increasing influent CNR led to a decrease in microbial α-diversity and niche width. Genera involved in nitrogen removal and denitrification, such as Rhodobacter, Desulfovibrio, and Zoogloea, were enriched under medium/high CNR conditions, resulting in higher nitrate (NO3--N) removal (up to 99 %) than that under lower CNR conditions (<60 %). Environmental factors, including water temperature (WT), pH, and phosphorus (P), along with CNR-induced COD and NO3--N play important roles in microbial succession in HFCWs. The genus Nitrospira, which is involved in nitrification, exhibited a significant negative correlation (p < 0.05) with WT, COD, and P. Co-occurrence network analysis revealed that increasing influent CNR reduced the complexity of the network structure and increased microbial competition. Analysis using null models demonstrated that the microbial community assembly in HFCWs was primarily driven by stochastic processes under increasing influent CNR conditions. Furthermore, HFCWs with more stochastic microbial communities exhibited better denitrification performance (NO3--N removal). Overall, this study enhances our understanding of nutrient removal, microbial co-occurrence, and assembly mechanisms in CWs under varying influent CNRs.

Zygosity-based sex determination in a butterfly drives hypervariability of Masculinizer.

Nature has devised many ways of producing males and females. Here, we report on a previously undescribed mechanism for Lepidoptera that functions without a female-specific gene. The number of alleles or allele heterozygosity in a single Z-linked gene (BaMasc) is the primary sex-determining switch in Bicyclus anynana butterflies. Embryos carrying a single BaMasc allele develop into WZ (or Z0) females, those carrying two distinct alleles develop into ZZ males, while (ZZ) homozygotes initiate female development, have mismatched dosage compensation, and die as embryos. Consequently, selection against homozygotes has favored the evolution of spectacular allelic diversity: 205 different coding sequences of BaMasc were detected in a sample of 246 females. The structural similarity of a hypervariable region (HVR) in BaMasc to the HVR in Apis mellifera csd suggests molecular convergence between deeply diverged insect lineages. Our discovery of this primary switch highlights the fascinating diversity of sex-determining mechanisms and underlying evolutionary drivers.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

Lipidomic Risk Score to Enhance Cardiovascular Risk Stratification for Primary Prevention.

BACKGROUND: Accurate risk stratification is vital for primary prevention of cardiovascular disease (CVD). However, traditional tools such as the Framingham Risk Score (FRS) may underperform within the diverse intermediate-risk group, which includes individuals requiring distinct management strategies. OBJECTIVES: This study aimed to develop a lipidomic-enhanced risk score (LRS), specifically targeting risk prediction and reclassification within the intermediate group, benchmarked against the FRS. METHODS: The LRS was developed via a machine learning workflow using ridge regression on the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab; n = 10,339). It was externally validated with the Busselton Health Study (n = 4,492), and its predictive utility for coronary artery calcium scoring (CACS)-based outcomes was independently validated in the BioHEART cohort (n = 994). RESULTS: LRS significantly improved discrimination metrics for the intermediate-risk group in both AusDiab and Busselton Health Study cohorts (all P < 0.001), increasing the area under the curve for CVD events by 0.114 (95% CI: 0.1123-0.1157) and 0.077 (95% CI: 0.0755-0.0785), with a net reclassification improvement of 0.36 (95% CI: 0.21-0.51) and 0.33 (95% CI: 0.15-0.49), respectively. For CACS-based outcomes in BioHEART, LRS achieved a significant area under the curve improvement of 0.02 over the FRS (0.76 vs 0.74; P < 1.0 × 10-5). A simplified, clinically applicable version of LRS was also created that had comparable performance to the original LRS. CONCLUSIONS: LRS, augmenting the FRS, presents potential to improve intermediate-risk stratification and to predict atherosclerotic markers using a simple blood test, suitable for clinical application. This could facilitate the triage of individuals for noninvasive imaging such as CACS, fostering precision medicine in CVD prevention and management.

Working memory performance and neural activity in prefrontal cortex of peripubertal monkeys.

The dorsolateral prefrontal cortex matures late into adolescence or early adulthood. This pattern of maturation mirrors working memory abilities, which continue to improve into adulthood. However, the nature of the changes that prefrontal neuronal activity undergoes during this process is poorly understood. We investigated behavioral performance and neural activity in working memory tasks around the time of puberty, a developmental event associated with the release of sex hormones and significant neurological change. The developmental stages of male rhesus monkeys were evaluated with a series of morphometric, hormonal, and radiographic measures. Peripubertal monkeys were trained to perform an oculomotor delayed response task and a variation of this task involving a distractor stimulus. We found that the peripubertal monkeys tended to abort a relatively large fraction of trials, and these were associated with low levels of task-related neuronal activity. However, for completed trials, accuracy in the delayed saccade task was high and the appearance of a distractor stimulus did not impact performance significantly. In correct trials delay period activity was robust and was not eliminated by the presentation of a distracting stimulus, whereas in trials that resulted in errors the sustained cue-related activity was significantly weaker. Our results show that in peripubertal monkeys the prefrontal cortex is capable of generating robust persistent activity in the delay periods of working memory tasks, although in general it may be more prone to stochastic failure than in adults.

Current status and prospects of GREM1 research in cancer (Review).

GREM1 is a secreted protein that antagonizes bone morphogenetic proteins (BMPs) and participates in critical biological processes, including embryonic development, organogenesis and tissue differentiation. Gremlin 1 (GREM1) is also an inhibitor of TGF-ß and a ligand for vascular endothelial growth factor receptor 2. In addition, GREM1 can induce cells, participate in the process of epithelial-mesenchymal transition, and then participate in tumor development. GREM1 has a variety of biological functions and can participate in the malignant progression of a variety of tumors through the BMP signaling pathway. GREM1 also can inhibit TGF-ß in some tumors, thereby inhibiting tumors, and its involvement in tumor development varies in different types of cancer. The present review examines the role and function of GREM1 in tumors. GREM1 is expressed in a variety of tumor types. GREM1 expression can affect the epithelial-mesenchymal transformation of tumor cells. GREM1 has been studied in breast and colon cancer, and its potential role is to promote cancer. However, in pancreatic cancer, which was found to act differently from other cancer types, overexpression of GREM1 inhibits tumor metastasis. The present review suggests that GREM1 can be a diagnostic and prognostic indicator. In future studies, the study of GREM1 based on single-cell sequencing technology will further clarify its role and function in tumors.