Weak Effect Research Articles

Artesunate, EDTA, and colistin work synergistically against MCR-negative and -positive colistin-resistant Salmonella.

Discovering new strategies to combat the multidrug-resistant bacteria constitutes a major medical challenge of our time. Previously, artesunate (AS) has been reported to exert antibacterial enhancement activity in combination with β-lactam antibiotics via inhibition of the efflux pump AcrB. However, combination of AS and colistin (COL) revealed a weak synergistic effect against a limited number of strains, and few studies have further explored its possible mechanism of synergistic action. In this article, we found that AS and EDTA could strikingly enhance the antibacterial effects of COL against mcr-1- and mcr-1+ Salmonella strains either in vitro or in vivo, when used in triple combination. The excellent bacteriostatic effect was primarily related to the increased cell membrane damage, accumulation of toxic compounds and inhibition of MCR-1. The potential binding sites of AS to MCR-1 (THR283, SER284, and TYR287) were critical for its inhibition of MCR-1 activity. Additionally, we also demonstrated that the CheA of chemosensory system and virulence-related protein SpvD were critical for the bacteriostatic synergistic effects of the triple combination. Selectively targeting CheA, SpvD, or MCR using the natural compound AS could be further investigated as an attractive strategy for the treatment of Salmonella infection. Collectively, our work opens new avenues toward the potentiation of COL and reveals an alternative drug combination strategy to overcome COL-resistant bacterial infections.

Temperature influences resource selection and predation risk tolerance in a climate generalist

ContextThermal conditions can influence animal behavior and predator–prey dynamics. Understanding the effects of temperature on animals and their interactions is of increasing importance given predictions for global warming.ObjectivesWe determined how temperature influenced avoidance of risky areas and habitat selection in a climate generalist, white-tailed deer (Odocoileus virginianus; hereafter “deer”), and how the effect varied between night and day in a system characterized by extreme heat and high predation risk from Florida panther (Puma concolor coryi).MethodsWe collected GPS locations of 224 (79 M, 145F) deer from June through September 2015–2018 in southwestern Florida, USA. We fit step-selection functions with interactions between ambient temperature and covariates including landcover and a spatial model of predation risk informed by panther kill sites.ResultsAvoidance of high-risk areas decreased with rising temperatures during night and day, indicating deer were less predation risk averse when balancing higher thermoregulatory costs. As temperatures increased during the day, deer increased avoidance of marshes and hardwood hammocks. However, temperature had weaker effects on habitat selection at night with only a moderate increase in selection of marshes with increasing temperatures.ConclusionsIn systems characterized by extreme heat, thermal conditions can have strong effects on animal behavior and species interactions. While climate generalists like deer have high tolerances to thermal stress, temperature still influenced predation risk tolerance and habitat selection of deer during both day and night periods. These responses are likely even stronger in species with narrower thermal tolerances (i.e., climate specialists). Thermal conditions are an important and potentially underappreciated driver of species interactions that is likely to become more significant with climate change.

A multilayer snowflake resonator metamaterial for low-frequency broadband sound absorption

Abstract Low-frequency broadband sound-absorbing structures with smaller thicknesses are the focus of research in noise control. Based on the principle of Helmholtz resonant cavity and the internal spacer chamber division structure, a multilayer snowflake resonator metamaterial (MLSRCM) is proposed. The MLSRCM model is investigated using theoretical and simulation methods, and it is concluded that the MLSRCM has excellent sound absorption performance in the frequency range of 450–950 Hz with a thickness of only 28 mm. This mainly originated from the parallel connection of multi-units as well as the application of the weak resonance effect of coherent coupling and the full utilization of space. The broadband sound absorption mechanism in MLSRCM is theoretically investigated by analyzing the complex frequency plane. Subsequently, the sound absorption mechanism of the structure is further analyzed in terms of sound velocity and power dissipation density. The results show that the MLSRCM has excellent low-frequency broadband acoustic absorption performance, which provides a reference for the design of new acoustic-absorbing metamaterials with small thicknesses.

The effect of emotional intelligence on nurses’ job performance: the mediating role of moral intelligence and occupational stress

BackgroundAlthough previous studies have linked emotional intelligence to nurses’ job performance, research lacks how moral intelligence and occupational stress mediate this relationship. Addressing this gap is essential for improving nursing care outcomes. This study aims to determine the mediating effect of moral intelligence and occupational stress in this relationship among Iranian nurses.MethodsThis descriptive cross-sectional correlational study was conducted in Urmia Teaching Hospital from February to April 2022. Six hundred and twenty-one nurses were recruited using quota sampling. Data were collected using a demographic questionnaire, Lenik and Kiel’s Moral Intelligence Questionnaire (LK-MIQ), Siberia Schering’s Emotional Intelligence Questionnaire (SS-EISQ), Patterson’s Job Performance Questionnaire (P-JPQ), and the Nursing Stress Scale (NSS). Data were analyzed using IBM SPSS ver. 23 and Smart-PLS ver. 3.0.ResultsThe effect of emotional intelligence on job performance was positive, direct, and weak (β = 0.099, t-value = 2.285, p = 0.023). Emotional intelligence had a negative, direct, and weak effect on moral intelligence (β = − 0.257, t-value = 4.754, p = 0.000) and a negative, direct, and moderate effect on occupational stress (β = − 0.316, t-value = 6.482, p = 0.000). Moral intelligence mediates the relationship between emotional intelligence and occupational stress (β = 0.0842, 95% CI: 0.0532, 0.1194). However, the mediating role of occupational stress between emotional intelligence and job performance was not supported (β = 0.003, 95% CI: − 0.0139, 0.0184).ConclusionMoral and emotional intelligence should be key criteria for selecting nursing staff and managers to create a safe, low-stress environment that boosts nurses’ job performance. Healthcare managers should promote nurses’ emotional intelligence by offering practical courses for enhancing nurses’ self-awareness, self-management, social awareness, and relationship management skills. It is essential to support moral intelligence by organizing educational classes that improve their integrity, responsibility, compassion, and forgiveness.

Influence of Media Disorder on DNA Melting: A Monte Carlo Study.

We explore the melting of a lattice DNA in the presence of atmospheric disorder, which mimics the crowded environment inside the cell nucleus, using Monte Carlo simulations. The disorder is modeled by randomly retaining lattice sites with probability p while diluting the rest, rendering them unavailable to the DNA. By varying the disorder over a wide range from p = 1 (zero disorder) up to the percolation critical point pc = 0.3116, we show the melting temperature (Tm) to increase nearly linearly with disorder up to p ≈ 0.6, while strong nonlinearity enters for p ≲ 0.6. Associated changes in the bubble statistics have been investigated, showing a substantial change in the bubble size exponent at corresponding melting points for p ≤ 0.5. Based on these findings, two distinct disorder regimes showing weak and strong effects on melting have been identified. For simulations, we use the pruned and enriched Rosenbluth method in conjunction with a depth-first implementation of the Leath algorithm to generate the underlying disorder.

A New Trick of Old Dogs: Can Kappa Opioid Receptor Antagonist Properties of Antidepressants Assist in Treating Treatment-Resistant Depression (TRD)?

Background/Objectives: Approximately one in five individuals will experience major depressive disorder (MDD), and 30% exhibit resistance to standard antidepressant treatments, resulting in a diagnosis of treatment-resistant depression (TRD). Historically, opium was used effectively to treat depression; however, when other medications were introduced, its use was discontinued due to addiction and other hazards. Recently, kappa opioid receptor (KOR) antagonism has been proposed as a potential mechanism for treating TRD. The main research question is whether commonly used psychotropic medications possess KOR antagonist properties and whether this characteristic could contribute to their efficacy in TRD. Methods: We investigated the antinociceptive effects of many psychotropic medications and their interactions with the opioid system. Mice were tested with a hotplate or tail-flick after being injected with different doses of these agents. Results: The antidepressants mianserin and mirtazapine (separately) induced dose-dependent antinociception, each yielding a biphasic dose–response curve. Similarly, the antidepressant venlafaxine produced a potent effect and reboxetine produced a weak effect. The antipsychotics risperidone and amisulpride exhibited a dose-dependent antinociceptive effect. The sedative–hypnotic zolpidem induced a weak bi-phasic dose-dependent antinociceptive effect. All seven psychotropic medications elicited antinociception, which was reversed by the non-selective opiate antagonist naloxone and, separately, by the kappa-selective antagonist Nor-BNI. Conclusions: Clinical studies are mandatory to establish the potential efficacy of augmentation of the treatment with antidepressants with these drugs in persons with treatment-resistant depression and the optimal dosage of medications prescribed. We suggest a possible beneficial effect of antidepressants with kappa antagonistic properties.

Anisotropy of free-surface wave turbulence induced by a horizontal magnetic (electric) field

This work investigates the effects of anisotropy of free-surface wave turbulence under the influence of an external horizontal magnetic (electric) field based on direct numerical simulation technique. As the field increases, the surface wave system passes into the magnetohydrodynamic (MHD) turbulence regime with the formation of anisotropic condensate of capillary waves slowly propagating perpendicular to the external field. In the high field regime, the effect of the formation of discrete levels of frequency broadening in the space–time spectrum of capillary waves is reported for the first time. The performed correlation analysis showed that the resonance curve of the three-wave interaction is compressed with increasing field. This process leads to a non-local energy transfer from large-scale MHD waves to the small-scale capillary waves. Thus, discrete frequency levels in the spectrum of capillary waves arise as a result of the resonant decay of a MHD wave into secondary harmonics. Despite the anisotropy, the angle-averaged spectrum of surface elevations agrees well with the analytical estimate obtained under the assumption of isotropic wave propagation. We explain this contradiction by the fact that magnetic energy fluctuations on the liquid surface are distributed quasi-isotropically, and the anisotropic coherent condensate of capillary waves has a weak effect on the turbulence spectrum.

SENP2 negatively regulates RIG-I/MDA5 mediated innate immunity in black carp.

Mammalian SUMO specific peptidase 2 (SENP2) plays vital roles in a variety of biological procedures including the immune response. However, the effects of teleost SENP2 are still mostly unexplored. In this study, the SENP2 of black carp (Mylopharyngodon piceus) was cloned and characterized. The open reading frame of black carp SENP2 (bcSENP2) consists of 1800 nucleotides, which encode 600 amino acids. The reporter assay results showed that over-expression of bcSENP2 alone had a weak effect on interferon (IFN) promoter transcription activity, whereas it significantly reduced bcMDA5/bcRIG-I mediated IFN promoter transcription activity. The interaction between bcSENP2 and bcMDA5 or bcRIG-I was detected by immunoprecipitation experiments. The plaque assay and qPCR results indicated that bcMDA5 or bcRIG-I mediated antiviral capacity was attenuated by bcSENP2, while knockdown of bcSENP2 led to enhanced antiviral resistance to SVCV in host cells. In addition, the expression level of bcMDA5/bcRIG-I protein was attenuated by co-expressed bcSENP2 and MG132 treatment rescued this attenuating effect. All of these data support the conclusion that bcSENP2 inhibits bcMDA5/bcRIG-I mediated antiviral signaling by enhancing ubiquitin-proteasome mediated degradation of bcMDA5/bcRIG-I in black carp.

Comprehensive Metabolomics Profiling and Bioactivity Study of Lycium shawii (Awsaj) Extracts with Particular Emphasis on Potential Anti-Malarial Properties

Background/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.

Three new polyketides isolated from the Karst cave-derived Streptomyces sp. FD-2-6

Three new polyketides, actinofuranones J (1) and K (2), nocapyrone S (3), with one known compound nocapyrone Q (4) were isolated from the culture broth of a Karst cave-derived Streptomyces sp. (FD-2-6). Their structures were elucidated by comprehensive analysis of NMR spectroscopic data, HR-MS and electronic circular dichroism (ECD) data. The antitumour and antibacterial activities of 1-4 were investigated by examining their IC50 and MIC values in MCF-7 human breast cancer cells, human hepatocellular carcinoma HepG2 cells and human cervical cancer Hela cells, and Klebsiella pneumoniae sp, Pseudomonas aeruginosa sp, Mycolicibacterium smegmatis sp, Escherichia coli sp, Staphylococcus aureus sp. Compounds 1-4 showed weak inhibitory effect on antitumour activity on MCF-7 human breast cancer cells, and human cervical cancer Hela cells.

Weak traction effect modulates anionic solvation transition for stable-cycling and fast-charging lithium metal batteries

Weak traction effect modulates anionic solvation transition for stable-cycling and fast-charging lithium metal batteries

Undisturbed velocity recovery with transient and weak inertia effects in volume-filtered simulations of particle-laden flows

Undisturbed velocity recovery with transient and weak inertia effects in volume-filtered simulations of particle-laden flows

Chlorhexidine-loaded microneedles for treatment of oral diseases.

Chlorhexidine (CHX) is a gold standard therapeutic agent against clinical oral pathogens. However, its oral use is limited due to unpleasant taste, alteration in taste buds, staining of teeth and mucous membranes. Therefore, CHX-loaded PLGA microneedles (MNs) were fabricated for local and controlled release in the oral cavity, using a casting mold method. The MNs were well-formed with sharp MN tips and flat baseplates, showing quadrangular pyramidal shapes with average needle height and base width of about 500 and 200µm, respectively. CHX was successfully incorporated into the PLGA-based MNs, exhibiting high encapsulation efficiency. CHX-PLGA MNs were further characterized in terms of ATR-FTIR and DSC, indicating intermolecular interactions between CHX and PLGA. In vitro CHX release exhibited an initial burst release within the first 24h, accompanied by a slower release rate, reaching cumulative release of ca. 56% after 10days. The antibacterial effect of CHX-PLGA MNs on Streptococcus mutans (S. mutans) was evaluated using different techniques. In agar diffusion assay, the MNs displayed sustained antimicrobial activity over 8days, while they significantly reduced the bacterial growth of S. mutans on the first 4days in a planktonic experimental setup. No antibacterial effect was recorded for the blank PLGA MNs that served as a control group. Interestingly, CHX-PLGA MNs eliminated biofilm formation and metabolic activity for 3days compared with biofilm formed in the presence of blank MNs. Then, a rebound effect was recorded. A weak antibiofilm effect and anti-metabolic activity was observed when MNs tested against pre-formed biofilm. Taken together, CHX-PLGA MNs hold promise as a viable delivery modality for localized and sustainedantimicrobial activity in the oral cavity. Further research is required to optimize the formulation and assess efficacy and safety in clinical settings.

Nano-biochar reduces sustainable remediation of cadmium-contaminated soil more than micro-biochar: evidence from cadmium removal and Eisenia foetida toxicity

Micro- (M-BC) and nano-biochar (N-BC) particles are ready to be disintegrated from biochar (BC), which is extensively applied to remediate heavy metal-contaminated soil. Still, its effects on the remediation efficiency remain poorly understood. This study investigated the interactions between the BC particles (M-BC and N-BC) and Eisenia foetida (E. foetida) in cadmium (Cd)-contaminated soils. Results indicated that M-BC has weak negative effect on E. foetida with survival rates of ≥85% as it is failed to be internalized. The interactive effects between M-BC/N-BC and Cd reduced the mobility of Cd, leading to low avoidance behavior of E. foetida. The synergistic effect of 0.1% M-BC and E. foetida caused pH regulation, BC diffusion and alternation of soil microbial community in the soil. This favoured the remediation of Cd-contaminated soils with 56.2% Cd fixation efficiency identified. Conversely, internalization of Cd-loaded N-BC by E. foetida was recorded when 0.1% N-BC was amended in the soil. This triggered DNA damage, antioxidant suppression, antiapoptotic inhibition, digestion impairment, reproductive decline, and survival rates reduction (55%) in E. foetida, indicating the essential role of E. foetida in the soil is likely to be depressed. These findings are helpful to understand the potential negative effects of BC application in soil remediation.

Reg-eQTL: Integrating transcription factor effects to unveil regulatory variants.

Regulatory single-nucleotide variants (rSNVs) in noncoding regions of the genome play a crucial role in gene transcription by altering transcription factor (TF) binding, chromatin states, and other epigenetic modifications. Existing expression quantitative trait locus (eQTL) methods identify genomic loci associated with gene-expression changes, but they often fall short in pinpointing causal variants. We introduce reg-eQTL, a computational method that incorporates TF effects and interactions with genetic variants into eQTL analysis. This approach provides deeper insights into the regulatory mechanisms, bringing us one step closer to identifying potential causal variants by uncovering how TFs interact with SNVs to influence gene expression. This method defines a trio consisting of a genetic variant, a target gene, and a TF and tests its impact on gene transcription. In comprehensive simulations, reg-eQTL shows improved power of detecting rSNVs with low population frequency, weak effects, and synergetic interaction with TF as compared to traditional eQTL methods. Application of reg-eQTL to GTEx data from lung, brain, and whole-blood tissues uncovered regulatory trios that include eQTLs and increased the number of eQTLs shared across tissue types. Regulatory networks constructed on the basis of these trios reveal intricate gene regulation across tissue types.

Influence of free-floating plant species richness and composition on water quality improvement

ABSTRACT Background The link between species richness and ecosystem services remains a central question in ecology. Aims To evaluate the effect of composition and plant richness on water quality improvement. Methods Thirty-nine mesocosms (65 L) were divided into four quadrants and were either planted in monocultures, or in 2- or 4-species combinations. Mesocosms were fed with synthetic wastewater during one growing season and outflow samples were collected weekly for physico-chemical analyses. Results Pollutant removal efficiency varied among plant species and species combinations. Eichhornia crassipes outperformed the other plant species and was the only one whose presence in a plant combination had a positive effect on pollutant removal. Species richness had a small but highly significant effect on nitrogen removal, with 2-species and 4-species systems outperforming by 4% and 5%, respectively, the average removal of the monocultures. The removal efficiency of a combination of two species was occasionally better than the average of these species in monocultures. However, higher plant species richness never showed greater treatment performance over the most efficient monoculture of its constituent species. Conclusions Our study showed some weak but significant biodiversity effects of free-floating plant species on water quality improvement. Nevertheless, total plant biomass remained a better predictor of water purification capacity than species richness.

Uropygial gland microbiota of nearctic-neotropical migrants vary with season and migration distance.

Symbiotic microbiota are important drivers of host behaviour, health, and fitness. While most studies focus on humans, model organisms, and domestic or economically important species, research investigating the role of host microbiota in wild populations is rapidly accumulating. Most studies focus on the gut microbiota; however, skin and other glandular microbiota also play an important role in shaping traits that may impact host fitness. The uropygial gland is an important source of chemical cues and harbours diverse microbes that could mediate chemical communication in birds, so determining the factors most important in shaping host microbiota should improve our understanding of microbially-mediated chemical communication. Hypothesizing that temporal, geographic, and taxonomic effects influence host microbiota, we evaluated the effects of season, migration distance, and taxonomy on the uropygial gland microbiota of 18 passerine species from 11 families. By sampling 473 birds at a single stopover location during spring and fall migration and using 16S rRNA sequencing, we demonstrate that season, followed by migration distance, had the strongest influence on uropygial gland microbial community composition. While statistically significant, taxonomic family and species had only weak effects on gland microbiota. Given that temporal effects on gland microbiota were nearly ubiquitous among the species we tested, determining the consequences of and mechanisms driving this seasonal variation are important next steps.

Translation, cross-cultural adaptation, and psychometric properties of the Finnish version of the Malocclusion Impact Questionnaire (MIQ).

This study aimed to translate and adapt the Malocclusion Impact Questionnaire (MIQ) into Finnish; to estimate its psychometric properties when applied to Finnish adolescents; and to estimate the effect of demographic characteristics on the perceived impact of malocclusion. The Finnish version of MIQ (MIQ-Fi) was established through translation, back-translation, and a pilot study. Psychometric properties were estimated using factorial validity (confirmatory factor analysis [CFA]), convergent validity (Average Variance Extracted [AVE]), and reliability (αordinal and ω). Structural Equation Model estimated the effect of demographic characteristics on malocclusion impact. A total of 268 Finnish adolescents participated in the study (mean age=13.4 [standard deviation, SD=1.5] years, 48.5% girls). MIQ-Fi factor model presented an adequate fit to the data after refinements (CFA: comparative fit index [CFI]=0.96, Tucker-Lewis index [TLI]=0.95, standardized root mean square residual [SRMR]=0.08, exclusion of 4 items and 1 correlation between items error). Convergent validity (AVE=0.61) and reliability (αordinal and ω≥0.90) were adequate. Gender and self-reported need for orthodontic treatment had moderate effects on malocclusion impact (βstandardized=0.36 and 0.30, respectively, p<0.01), while other demographic characteristics had weak effects (βstandardized<|0.18|, p<0.04). MIQ-Fi demonstrated adequate psychometric properties and can measure malocclusion impact in Finnish adolescents. Demographic characteristics had weak to moderate effect on the malocclusion impact.

Improving Low‐Temperature Tolerance of a Lithium‐Ion Battery by a Localized High‐Concentration Electrolyte Based on the Weak Solvation Effect

Improving Low‐Temperature Tolerance of a Lithium‐Ion Battery by a Localized High‐Concentration Electrolyte Based on the Weak Solvation Effect

Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis.

Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects. MEDLINE was searched with the keyword "esketamine" on March 24, 2024, using the PRISMA method. Data processing and statistical analysis were performed with R, version 4.3.3, and the meta-analysis was performed with the METAFOR package. Of 1,115 articles initially identified, 87 were included for analysis and discussion. At weeks 2-4, randomized controlled trials were mostly negative or failed; however, the meta-analysis returned a weak but significant positive effect for depression (effect size range, 0.15-0.23 at weeks 2-4), similar to augmentation strategies with atypical antipsychotics for treatment-resistant depression. The effect size concerning suicidality was not significant at any time point. The sensitivity analysis produced the same results. The study findings suggest that esketamine's efficacy as an add-on to antidepressants is modest in treatment-resistant depression (similar to augmentation strategies with atypical antipsychotics) and is absent against suicidality itself. These findings need to be considered in light of esketamine's abuse potential and the fact that long-term effects are still not fully known. Some alarming signs concerning deaths and emerging suicidality during the testing phase are discussed, along with other regulatory issues.