Association between dietary fatty acids and urinary incontinence.

Background: Dietary nutrient intake contributes to urination; however, the association between dietary nutrient intake, especially that of fat, and urinary incontinence (UI) is not well understood. The most common types of UI include stress UI (SUI) and urgency UI (UUI). Objective: To investigate the potential effect(s) of dietary fat intake on UI and explore its mechanism of action in relation to body mass index (BMI). Methods: A cross-sectional survey of data from 15,121 individuals (20-85 years of age) from the National Health and Nutrition Examination Survey (2001-2008), a random population-based sample, was performed. Data regarding dietary nutrient intake were collected through 24 h dietary recall interviews. UI and covariate data were collected through in-person interviews. UI was assessed according to the American Urological Association Symptom Index. The odds ratio (OR) for SUI and UUI were calculated using multivariate logistic regression analysis. The mediation effect was estimated using observational mediation analysis. Results: Higher total fat intake was positively associated with increased odds for developing UI (OR 1.44 [95% confidence interval (CI) 1.08-1.93]). Females who consumed more saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were more likely to develop SUI. BMI partially explained the association between total fat, SFA, MUFA, and PUFA and SUI; the proportions of the mediation effect of BMI were 14.7%, 13.0%, 18.7%, and 16.3%, respectively. Conclusions: Results of this study emphasize the key role of dietary fat intake in the prevalence of UI. Higher fat intake was positively associated with UI and BMI partially mediated the effect of fat intake on SUI.

Regioselective hydroformylation of propene catalysed by rhodium-zeolite.

Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.

Nickel-Catalyzed Chemoselective Carbomagnesiation for Atroposelective Ring-Opening Difunctionalization.

There is a pressing need for methods that can connect enantioenriched organic compounds with readily accessible building blocks via asymmetric functionalization of unreactive chemical bonds in organic synthesis and medicinal chemistry. Herein, the asymmetric chemoselective cleavage of two unactivated C(Ar)-O bonds in the same molecule is disclosed for the first time through an unusual nickel-catalyzed carbomagnesiation. This reaction facilitates the evolution of a novel atroposelective ring-opening difunctionalization. Utilizing readily available dibenzo bicyclic substrates, diverse valuable axially chiral biaryls are furnished with high efficiencies. Synthetic elaborations showcase the application potential of this method. The features of this method include good atom-economy, multiple roles of the nucleophile, and a simple catalytic system that enables the precise magnesiation of an α-C(Ar)-O bond and arylation of a ß-C(Ar)-O bond.

Whole transcriptome sequencing reveals key genes and ceRNA regulatory networks associated with pimpled eggs in hens.

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

Unveiling the hidden risks: Pesticide residues in aquaculture systems.

The present study systematically assessed the presence and ecological risks of 79 pesticides in various aquaculture systems, namely pond aquaculture (PA), greenhouse aquaculture (GA), and raceway aquaculture (RA) at different aquaculture stages, along with evaluating the pesticide removal of four tailwater treatment systems. Sixteen herbicides and two fungicides were identified, with the total concentrations ranging from 8.33 ng/L to 3248.45 ng/L. The PA system demonstrated significantly higher concentrations (p < 0.05) and a wider range of pesticide residues compared to the GA and RA systems. Prometryn, simetryn, atrazine, and thifluzamide were found to be the predominant pesticides across all three aquaculture modes, suggesting their significance as pollutants that warrant monitoring. Additionally, the findings indicated that the early aquaculture stage exhibits the highest levels of pesticide concentration, underscoring the importance of heightened monitoring and regulatory interventions during this phase. Furthermore, among the four tailwater treatment systems analyzed, the recirculating tailwater treatment system exhibited the highest efficacy in pesticide removal. A comprehensive risk assessment revealed minimal ecological risks in both the aquaculture and tailwater environments. However, the pesticide mixtures present high risks to algae and low to medium risks to aquatic invertebrates and fish, particularly during the early stages of aquaculture. Simetryn and prometryn were identified as high-risk pesticides. Based on the prioritization index, simetryn, prometryn, diuron, and ametryn are recommended for prioritization in risk assessment. This study offers valuable data for pesticide control and serves as a reference for the establishment of a standardized pesticide monitoring and management system at various stages of aquaculture.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.

Flexible Tactile Sensors for 3D Force Detection.

As tactile force sensing has become increasingly significant in the field of machine haptics, achieving multidimensional force sensing remains a challenge. We propose a 3D flexible force sensor that consists of an axisymmetric hemispherical protrusion and four equally sized quarter-circle electrodes. By simulating the device using a force and electrical field model, it has been found that the magnitude and direction of the force can be expressed through the voltage relationship of the four electrodes when the magnitude of the shear force remains constant and its direction varies within 0-360°. The experimental results show that a resolution of 15° can be achieved in the range 0-90°. Additionally, we installed the sensor on a robotic hand, enabling it to perceive the magnitude and direction of touch and grasp actions. Based on this, the designed 3D flexible tactile force sensor provides valuable insights for multidimensional force detection and applications.

Healthy lifestyle and the risk of depression recurrence requiring hospitalisation and mortality among adults with pre-existing depression: a prospective cohort study.

BACKGROUND: Although lifestyle-based treatment approaches are recommended as important aspects of depression care, the quantitative influence of aggregated healthy lifestyles on depression recurrence and mortality remains unknown. OBJECTIVE: To investigate the association between healthy lifestyle and the risks of first-time hospitalisation for recurrent depression and mortality. METHODS: 26 164 adults with depression (mean (SD) age, 56.0 (7.9) years) were included from UK Biobank between 2006 and 2010 and followed up until 2022. Depression was defined as a physician's diagnosis in hospital admissions or the use of prescribed antidepressant medication. A weighted healthy lifestyle score (HLS) was calculated based on smoking, alcohol consumption, diet, sleep pattern, physical activity, social health, employment status and greenspace interaction. FINDINGS: Over a 13.3-year follow-up, 9740 cases of first-time hospitalisation due to depression recurrence and 1527 deaths were documented. Compared with the lowest HLS tertile, the highest tertile was associated with a 27% lower risk (HR=0.73, 95% CI 0.69 to 0.77) of first-time hospitalisation for depression recurrence and a 22% (HR=0.78, 95% CI 0.68 to 0.91) lower risk of mortality among adults with depression. Lower risks of first-time hospitalisation for depression recurrence were observed among those who smoked less, drank more alcohol, followed healthier diets and sleep patterns, spent more time employed in current job or had greater exposure to greenspace. CONCLUSION AND IMPLICATIONS: Greater adherence to healthy lifestyle was associated with a lower risk of hospitalisation and mortality among adults with pre-existing depression. Incorporating behaviour modification as an essential part of clinical practice for depressed patients could complement medication-based therapies.

Impact of the Pre-Dehydration and Drying Methods on the Mass Transfer and Quality Attributes of Yak Milk Casein.

Drying is an important preservation method of casein. Traditional natural draining and drying processes have low efficiency, long processing time, and poor product quality, which urgently need to be improved. This study investigated the effects of pre-dehydration intensities (30 N 30 min (PreD1) and 50 N 30 min (PreD2)) and drying methods (including pulsed vacuum drying (PVD), infrared drying (IRD), and hot air drying (HAD)) on the drying kinetics, drying modeling, and quality of yak milk casein. These findings reveal that PreD2 and PVD both had a positive impact on shortening the drying time. Compared to other combined treatments, PreD2-PVD had the shortest drying time of 6 h. The Midilli-Kucuk mathematical model effectively predicted the drying of casein. The yak milk casein powder treated with PreD2-PVD possessed a higher content of gross compositions, superior color, lower levels of fat oxidation and 5-hydroxymethylfurfural (5-HMF), and higher emulsifying activity index (EAI) and emulsion stability index (ESI) values. Overall, combining pre-dehydration with PVD proved effective in improving the drying rate and maintaining a good quality of yak milk casein, showing promising potential for industrial applications.

Associations Between Recreational Screen Time and Brain Health in Middle-Aged and Older Adults: A Large Prospective Cohort Study.

OBJECTIVES: To investigate the associations of recreational screen time with risks of brain-related disorders (dementia, stroke, or Parkinson's disease) and neuroimaging features. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: A total of 407,792 participants from the UK Biobank who were free of dementia, stroke, or Parkinson's disease at enrollment (2006-2010). METHODS: TV viewing and time spent using the computer were self-reported at baseline. Among a subsample of 40,692 participants, neuroimaging features were measured by magnetic resonance imaging in 2014. Data were analyzed using Cox proportional hazard models, restricted cubic spline, and general linear regression models. RESULTS: During a median follow-up of 12.6 years, 5227 incident dementia, 6822 stroke, and 2308 Parkinson's disease cases were identified. Compared with TV viewing >0-1 h/d, watching TV ≥5 h/d was associated with higher risks of dementia (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.28-1.62), stroke (HR, 1.12; 95% CI, 1.01-1.25), and Parkinson's disease (HR, 1.28; 95% CI, 1.06-1.54). Moreover, we observed inverse associations between TV viewing time and both gray matter volume and hippocampus volume (Ptrend <.001). However, we did not observe the significant associations between discretional computer use and brain-related disorders or neuroimaging features. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that high TV viewing time is associated with increased risk of various brain-related disorders, highlighting recreational TV viewing could have an important impact on brain-related health.

Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.

Physical Activity, Mental Activity, and Risk of Incident Stroke: A Prospective Cohort Study.

BACKGROUND: Cumulative evidence suggests a correlation between physical or mental activity and the risk of stroke. However, the combined impact of these activities on stroke onset remains unexplored. This study identified physical and mental activity patterns using principal component analysis and investigated their associations with risk of incident stroke in the general population. METHODS: Our study was sourced from the UK Biobank cohort between 2006 and 2010. Information on physical and mental-related activities were obtained through a touch-screen questionnaire. The incident stroke was diagnosed by physicians and subsequently verified through linkage to Hospital Episode Statistics. Principal component analysis was used to identify potential physical and mental activity patterns. Cox proportional hazard regression models were performed to calculate hazard ratios (HRs) and 95% CIs of incident stroke, adjusting for potential confounders. RESULTS: The initial UK Biobank cohort originally consisted of 502 411 individuals, of whom a total of 386 902 participants (aged 38-79 years) without any history of stroke at baseline were included in our study. During a median follow-up of 7.7 years, 6983 (1.8%) cases of stroke were documented. The mean age of the included participants was 55.9 years, and the proportion of women was 55.1%. We found that multiple individual items related to physical and mental activity showed significant associations with risk of stroke. We identified 4 patterns of physical activity and 3 patterns of mental activity using principal component analysis. The adherence to activity patterns of vigorous exercise, housework, and walking predominant patterns were associated with a lower risk of stroke by 17% (HR, 0.83 [95% CI, 0.78-0.89]; 20% (HR, 0.80 [95% CI, 0.75-0.85]; and 20% (HR, 0.80 [95% CI, 0.75-0.86), respectively. Additionally, the transportation predominant pattern (HR, 1.36 [95% CI, 1.28-1.45) and watching TV pattern (HR, 1.43 [95% CI, 1.33-1.53) were found to be significantly associated with a higher risk of stroke. These associations remained consistent across all subtypes of stroke. CONCLUSIONS: Activity patterns mainly related to frequent vigorous exercise, housework, and walking were associated with lower risks of stroke and all its subtypes. Our findings provide new insights for promoting suitable patterns of physical and mental activity for primary prevention of stroke.

Immune-mediated diseases are associated with a higher risk of ALS incidence: a prospective cohort study from the UK Biobank.

Objective: The occurrence of immune-mediated diseases (IMDs) in amyotrophic lateral sclerosis (ALS) patients is widely reported. However, whether IMDs and ALS is a simple coexistence or if there exists causal relationships between the two has been a subject of great interest to researchers. Methods: A total of 454,444 participants from the prospective cohort of UK Biobank were recruited to investigate the longitudinal association between IMDs and ALS. Previously any IMDs and organ specific IMDs were analyzed in relation to the following incident ALS by Cox-proportional hazard models. Subgroup analyses were performed to explore the covariates of these relationships. Results: After adjusting for potential covariates, the multivariate analysis showed that any IMDs were associated with an increased risk of ALS incidence (HR:1.42, 95%CI:1.03-1.94). IMDs of the endocrine-system and the intestinal-system were associated with increased risk of ALS incidence (endocrine-system IMDs: HR:3.01, 95%CI:1.49-6.06; intestinal system IMDs: HR:2.07, 95%CI: 1.14-3.77). Subgroup analyses revealed that immune burden, including IMD duration and the severity of inflammation had specific effects on the IMD-ALS association. In participants with IMD duration≥10 years or CRP≥1.3mg/L or females, previous IMDs increased the risk of incident ALS; however, in participants with IMD duration <10 years or CRP<1.3mg/L or males, IMDs had no effect on incident ALS. Interpretation: Our study provides evidence that previous any IMDs and endocrine-system and the intestinal-system specific IMDs are associated with an increased risk of developing ALS in females, but not in males.

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti-triple-negative breast cancer efficacy in vitro and in vivo.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 µM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α-tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c-Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α-tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well-tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/ß-catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2-targeting drugs.

Accelerometer-measured physical activity, sedentary behavior, and risk of incident pelvic organ prolapse: a prospective cohort study in the UK Biobank.

BACKGROUND: Previous studies on physical activity (PA) and pelvic organ prolapse (POP) were largely limited to self-reported PA in athletes, soldiers, and women in postpartum. We aimed to investigate the association of accelerometer-measured PA and sedentary behavior with the risk of POP in middle-aged and elderly women. METHODS: In this prospective cohort derived from the UK Biobank, the intensity and duration of PA and sedentary behavior were measured with wrist-worn accelerometers over a 7-day period in 2013-2015 for 47,674 participants (aged 42.8-77.9 years) without pre-existing POP. Participants were followed up until the end of 2022, during which incident POP was ascertained mainly by the electronic health records. Multivariable-adjusted Cox proportional hazards models and restricted cubic splines were used to assess the associations of interest. Isotemporal substitution models were applied to test the effects of substituting a type of activity with equivalent duration of others. RESULTS: During a median follow-up of 8.0 years, 779 cases of POP were recorded. The duration of light-intensity PA (LPA) was positively whereas sedentary time was negatively associated with the risk of POP. Every additional 1 h/day of LPA elevated the risk of POP by 18% (95% confidence interval [CI], 10%-26%). In contrast, the risk decreased by 5% (95% CI, 0-8%) per 1 h/day increment in sedentary behavior. No associations were found between moderate-intensity PA (MPA) or vigorous-intensity PA (VPA) and POP, except that women who had a history of hysterectomy were more likely to develop POP when performing more VPA (53% higher risk for every additional 15 min/day). Substituting 1 h/day of LPA with equivalent sedentary time was associated with a 18% (95% CI, 11%-24%) lower risk of POP. The risk can also be reduced by 17% (95% CI, 7%-25%) through substituting 30 min/day of LPA with MPA. CONCLUSIONS: More time spent in LPA or less sedentary time was linked to an elevated risk of POP in middle-aged and elderly women, while MPA or VPA was not. Substituting LPA with equivalent duration of sedentary behavior or MPA may lower the risk of POP.

Apelin ameliorates sepsis-induced myocardial dysfunction via inhibition of NLRP3-mediated pyroptosis of cardiomyocytes.

Sepsis-induced myocardial dysfunction (SMD) is the major cause of death in sepsis. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)-mediated pyroptosis contributes to the occurrence and development of SMD. Although Apelin confers direct protection against SMD, the potential mechanisms remain unclear. This study aimed to determine whether Apelin protects against SMD via regulation of NLRP3-mediated pyroptosis of cardiomyocytes. Experimental SMD was induced in wild-type (WT) control mice and Apelin knockout (Apelin-/-) mice by cecal ligation and puncture (CLP). Neonatal mouse cardiomyocytes (NMCs) were treated with lipopolysaccharide (LPS) to simulate the physiological environment of SMD in vitro. The expression of Apelin was greatly decreased in the plasma from septic patients and septic mouse heart. Knockout of Apelin aggravated SMD, evidenced by decreased cardiac function, and increased cardiac fibrosis and NLRP3 inflammasome and pyroptosis levels in CLP-treated Apelin-/- mice compared with WT mice. Overexpression of Apelin activated the AMPK pathway and thereby inhibited NLRP3 inflammasome-mediated pyroptosis of NMCs induced by LPS in vitro These protective effects were partially abrogated by AMPK inhibitor. In conclusion, Apelin attenuated SMD by inhibiting NLRP3-mediated pyroptosis via activation of the AMPK pathway. Apelin may serve as a promising therapeutic target for SMD.

Unraveling the molecular mechanism for enhanced gas adsorption in mixed-metal MOFs via solid-state NMR spectroscopy.

The incorporation of multiple metal ions in metal-organic frameworks (MOFs) through one-pot synthesis can induce unique properties originating from specific atomic-scale spatial apportionment, but the extraction of this crucial information poses challenges. Herein, nondestructive solid-state NMR spectroscopy was used to discern the atomic-scale metal apportionment in a series of bulk Mg1-xCox-MOF-74 samples via identification and quantification of eight distinct arrangements of Mg/Co ions labeled with a 13C-carboxylate, relative to Co content. Due to the structural characteristics of metal-oxygen chains, the number of metal permutations is infinite for Mg1-xCox-MOF-74, making the resolution of atomic-scale metal apportionment particularly challenging. The results were then employed in density functional theory calculations to unravel the molecular mechanism underlying the macroscopic adsorption properties of several industrially significant gases. It is found that the incorporation of weak adsorption sites (Mg2+ for CO and Co2+ for CO2 adsorption) into the MOF structure counterintuitively boosts the gas adsorption energy on strong sites (Co2+ for CO and Mg2+ for CO2 adsorption). Such effect is significant even for Co2+ remote from Mg2+ in the metal-oxygen chain, resulting in a greater enhancement of CO adsorption across a broad composition range, while the enhancement of CO2 adsorption is restricted to Mg2+ with adjacent Co2+. Dynamic breakthrough measurements unambiguously verified the trend in gas adsorption as a function of metal composition. This research thus illuminates the interplay between atomic-scale structures and macroscopic gas adsorption properties in mixed-metal MOFs and derived materials, paving the way for developing superior functional materials.

Exogenous γ-Aminobutyric Acid (GABA) Enhanced Response to Abiotic Stress in Hypsizygus marmoreus by Improving Mycelial Growth and Antioxidant Capacity.

γ-Aminobutyric (GABA) acid is a nutrient and signaling molecule existing in many plants, participating in the regulation of metabolism and various physiological activities. Two strains of Hypsizygus marmoreus (a white variety and a brown variety) were investigated to study the impact of exogenous GABA on mycelial growth and the response to stress. Mycelial growth, microscopic morphology, antioxidant profile, and gad2 expression in H. marmoreu were investigated under salt, dehydration, or cold stress. The results indicated that 5 mM GABA stimulated mycelial growth under standard cultivation conditions, whereas GABA addition over 10 mM hindered the growth. Under salt, dehydration, or cold stress, treatment with 5 mM GABA significantly enhanced the mycelial growth rate and density of both H. marmoreus strains by promoting front hyphae branching. Meanwhile, the activities of key antioxidant enzymes such as peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) were enhanced by GABA, thereby augmenting the defensive network against abiotic stress. Additionally, gad2 expression and GABA concentration were increased under abiotic stresses as a resistance regulation response. The exogenous addition of GABA strengthened the upregulation of gad2 expression and GABA production. These findings indicated that exogenously adding low concentrations of GABA effectively enhanced the mycelial growth and antioxidant profile of H. marmoreus, thereby improving its resistance against stresses.

Molecular Investigation and Preliminary Validation of Candidate Genes Associated with Neurological Damage in Heat Stroke.

Heat stroke (HS) is a severe medical condition characterized by a systemic inflammatory response that may precipitate multi-organ dysfunction, with a particular predilection for inducing profound central nervous system impairments. We aim to employ bioinformatics techniques for the retrieval and analysis of genes associated with heat stroke-induced neurological damage. We performed a comprehensive analysis of the GSE64778 dataset from the Sequence Read Archive, resulting in the identification of 1178 significantly differentially expressed genes (DEGs). We retrieved 2914 genes associated with heat stroke from the GeneCards database and 2377 genes associated with heat stroke from the Comparative Toxicogenomics Database (CTD). The intersection of the top 300 DEGs in the GSE64778 dataset intersected with the search results of GeneCards and CTD, yielding 25 final candidates for DEGs associated with heat stroke. Gene Ontology functional annotation results indicated that the target genes were mainly involved in apoptosis, stress response, and negative regulation of cellular processes and function in processes such as protein dimerization and protein binding. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed a predominant enrichment of candidate target genes within the PI3K-AKT signaling pathway. Subsequent protein-protein interaction network analysis highlighted HSP90aa1 as a central gene, indicating its pivotal role by possessing the highest number of edges among the genes enriched in the PI3K-AKT signaling pathway. Quantitative reverse transcription-polymerase chain reaction analysis performed on blood samples from patients validated the expression of Hsp90aa1 in individuals exhibiting early neurological damage in HS, consistent with the findings from the mRNA bioinformatics analysis. Additionally, the bioinformatics analysis of the upstream microRNAs (miRNAs) regulating HSP90aa1 and the target miRNAs associated with candidate long non-coding RNAs (lncRNAs) identified three lncRNAs, eight miRNAs, and one mRNA in the regulatory network. The DIANA Tools database and algorithms were employed for pathway enrichment and correlation analysis, revealing a significant association between LOC102547734 and MIR-206-3p, with the latter being identified as a target binding site Moreover, the analysis unveiled a correlation between MIR-206-3p and HSP90aa1, implicating the latter as a potential target binding site within the regulatory network.

Structure-guided design of potent JAK1-selective inhibitors based on 4-amino-7H-pyrrolo[2,3-d]pyrimidine with anti-inflammatory efficacy.

In a continuous effort to develop Janus kinase 1 (JAK1)-selective inhibitors, a novel series of 4-amino-7H-pyrrolo[2,3-d]pyrimidine derivatives bearing the piperidinyl fragment were designed and synthesized according to a combination strategy. Through enzymatic assessments, the superior compound 12a with an IC50 value of 12.6 nM against JAK1 was identified and a 10.7-fold selectivity index over JAK2 was achieved. It was indicated that 12a displayed considerable effect in inhibiting the pro-inflammatory NO generated from lipopolysaccharide (LPS)-induced RAW264.7 macrophages, while on normal RAW264.7 cells, 12a exerted a weak cytotoxicity effect (IC50 = 143.3 µM). Furthermore, H&E stain assay demonstrated the conspicuous capacity of 12a to suppress CCl4-induced hepatic fibrosis levels in a dose-dependent manner in vivo. The binding model of 12a ideally reflects the excellent activity of JAK1 over the homologous kinase JAK2. Overall, 12a, a JAK1-selective inhibitor, exhibited potential for liver fibrosis and inflammatory diseases.