Search Results (1,096)

Against the backdrop of the rapid development of the platform economy, gig workers’ mental health and behavior impact both individual well-being and the long-term sustainability of platform operations. Based on the cognitive appraisal theory of emotion, this study reveals the nonlinear psychological mechanism through which perceived algorithmic management influences gig workers’ behavior. Using hierarchical regression and Bootstrap analysis on data from 385 Chinese gig workers, we examine mediating and moderating effects. The findings indicate that a U-shaped relationship between them: both excessively low and high algorithmic control intensify counterproductive behaviors, while moderate control suppresses them. Negative emotions mediate this effect, uncovering the mechanism by which algorithmic control influences behavior through emotional pathways. Locus of control moderates this relationship: externally controlled workers are more sensitive to algorithmic changes, amplifying the U-shaped effect, while internally controlled workers buffer negative emotions, reducing counterproductive behaviors. This study extends the cognitive appraisal theory of emotion to the context of algorithmic management, revealing the threshold effect of perceived control and the moderating role of individual attribution tendencies. It provides theoretical guidance for platform enterprises to optimize algorithmic design and guide gig workers’ behavior, thereby facilitating the coordinated development of dual sustainability for both gig workers and platform operations. Full article

Background: Gestational diabetes mellitus (GDM) poses a growing public health challenge worldwide due to its increasing prevalence, associated pregnancy complications, and long-term metabolic risks for both mothers and offspring. Genetic factors are known to contribute to GDM susceptibility, yet little is known about their relevance in ethnic Kazakh population. The primary objective of this study was to evaluate associations between selected candidate SNPs involved in β-cell function and the risk of GDM in a Kazakh cohort. Secondary objectives included the assessment of potential gene–gene interactions. Methods: We conducted a case–control study among 365 pregnant Kazakh women. Of these, 217 were diagnosed with GDM, and 148 had normal glucose tolerance. Clinical and genealogical data were collected. Eight candidate SNPs that were previously associated with GDM or glucose metabolism were genotyped. Logistic regression was used to assess associations between SNPs and GDM risk. Gene–gene interactions were evaluated using multifactor dimensionality reduction (MDR). Results: In univariate analysis, MTNR1B rs10830963 demonstrated a statistically significant association under the additive model (OR 0.61, 95% CI 0.42–0.89), indicating a potential protective effect of the C allele. However, this association was not statistically significant after multivariable adjustment (adjusted OR 0.58, 95% CI 0.32–1.03) and correction for multiple testing. In the adjusted analysis, TCF7L2 rs7903146 showed a significant association under the dominant model (adjusted OR 2.29, 95% CI 1.01–5.46); however, this finding did not remain significant following FDR correction. MDR analysis showed that the best two-locus model included IGF2BP2 rs4402960 and CDKAL1 rs7754840 (CVC = 6/10; testing accuracy = 0.558; permutation p < 0.001). The most stable interaction was observed for the three-locus model comprising IGF2BP2 rs4402960, MTNR1B rs10830963, and PPARG rs1801282 (CVC = 9/10; testing accuracy = 0.576; permutation p < 0.001). Conclusions: The findings suggest that common variants in IGF2BP2, CDKAL1, MTNR1B, TCF7L2, PPARG, and GCK do not exert strong individual effects on GDM susceptibility in this cohort of ethnic Kazakh women. Instead, the results are more consistent with a modest polygenic architecture characterized by small effect sizes and possible weak gene–gene interactions. MDR analysis identified statistically significant interaction models; however, their limited predictive accuracy indicates that these findings should be interpreted as exploratory. Full article

Central to the linkage of pain circuitry with the limbic system is its initial NAα2-mediated antinociceptive effect in acute pain models, followed by contradictory pronociceptive activation by the locus coeruleus seen in chronic pain models. Rats with a stable, long-term (>10 weeks) inflammatory compression of the trigeminal infraorbital nerve (FRICT-ION) preclinical model were given daily doxazosin, a slow-release NAα1 receptor antagonist, in weeks 8–10. Facial hypersensitivity was reversed back to baseline in male and female rats, but anxiety was only reduced in male animals. Doxazosin-decreased astrocytic activation was indicated by a decrease in both intracranial cathepsin B imaging in vivo and GFAP immunostaining in the somatosensory cortex and hippocampus. Doxazosin reduction in NAα1 receptor activation diminished glial-neuronal interactions, resulting in downstream reduction in pain-related behaviors. Other significant differences by sex included improved elevated zero maze anxiety measures only in males, and improved novel recognition scores only in females. Elevated thymus chemokine CXCL7 levels were reduced by doxazosin but only in male rats. These sexually dimorphic contradictions further complicate the understanding of the noradrenergic system’s involvement in nociception. The findings indicate that by reducing NAα1 receptor drive with doxazosin, the role of the locus coeruleus can be shifted back to NAα2-receptor-mediated pain inhibition. Full article

Background/Objectives: Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder caused by α-L-iduronidase (IDUA) deficiency, leading to progressive glycosaminoglycan (GAG) accumulation and severe joint involvement. Gene editing represents a promising alternative to restore localized enzyme production. Therefore, this study aimed to evaluate the feasibility, efficacy, and safety of in situ genome editing through intra-articular administration of a nonviral CRISPR/Cas9 system to increase localized IDUA expression in an MPS I mouse model. Methods: Cationic liposomes were formulated to deliver plasmids encoding the CRISPR/Cas9 system targeted to the ROSA26 locus along with an IDUA donor sequence. In vitro assays were performed in fibroblast-like synoviocytes (FLSs) isolated from MPS I mice to assess cytotoxicity, gene editing efficiency, and IDUA activity. In vivo, MPS I mice received intra-articular injections in the knee joints, either as a single dose (short-term study) or monthly for three months (long-term study). IDUA activity, GAG levels, and genome editing efficiency were evaluated in joint tissues, synovial fluid, serum, and major organs. Results: Gene-edited FLS showed sustained IDUA activity for up to 30 days with low cytotoxicity. In vivo, intra-articular administration resulted in a significant increase in IDUA activity in joint tissue and synovial fluid without detectable systemic IDUA. Long-term treatment led to persistent joint-localized IDUA activity, significant reductions (>50%) in GAG levels, and detectable genome editing in joint DNA. Conclusions: Intra-articular delivery of CRISPR/Cas9 via cationic liposomes enables safe and effective localized genome editing, representing a promising strategy for treating joint manifestations of MPS I. Full article

Background: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, yet the shared genetic variants underlying these conditions remain poorly understood. This study aimed to investigate shared genetic variants underlying lung function and glucose levels in middle-aged Chinese twins. Methods: In this exploratory analysis, we reanalyzed genotype data from a previously published northern Chinese twin sample, including 139 dizygotic and 238 monozygotic twin pairs from the Qingdao Twin Registry. Lung function traits (FEV1, FVC, and FEV1/FVC) and fasting plasma glucose (FPG) were jointly analyzed using a twin-based bivariate genome-wide association approach, followed by functional annotation and gene-based analyses. Variants showing suggestive associations were further examined in an independent UK Biobank Chinese sample. Results: A significant negative correlation between the FEV1/FVC ratio and FPG was revealed. The analysis identified 29 SNPs reaching genome-wide significance, with association signals primarily clustering at the 2q33.1 locus. Functional annotation indicated that most associated variants were non-coding, with several SNPs overlapping regulatory elements annotated to the SPATS2L locus. Gene-based analysis further supported the involvement of SPATS2L in the shared genetic architecture of the two traits. In the validation analysis, seven variants at the 2q33.1 locus showed nominal associations with consistent effect directions. Conclusions: This exploratory bivariate analysis provides evidence supporting shared genetic variants underlying pulmonary function and glucose regulation and offers insight into the genetic basis of COPD–T2DM comorbidity. Full article

Chilli pepper agroecosystems (Capsicum annuum L.) are increasingly threatened by cadmium (Cd) contamination, with emerging climatic stressors such as drought further exacerbating risks to food safety and crop productivity. This review synthesizes current evidence on microbiome-mediated Cd phytostabilisation in chilli pepper, with a particular focus on the roles of capsaicinoids and cultivar-specific genetic regulation in shaping rhizosphere microbial communities. Existing studies demonstrate that capsaicinoid-rich cultivars selectively recruit specialized rhizosphere microbes, enhancing root-level Cd sequestration and achieving Cd retention efficiencies of approximately 40–55%, thereby substantially restricting Cd translocation to edible fruit tissues. Multi-strain plant growth-promoting rhizobacteria (PGPR) consortia, especially when combined with structured organic amendments, have been reported to reduce fruit Cd and nickel (Ni) accumulation by more than 87% in contaminated soils. These responses are regulated by pungency-associated genetic loci, including Pun1 (pungency locus 1) and Pun4 (pungency locus 4) genes, which influence secondary metabolism and microbial assembly under metal stress conditions. The review highlights key knowledge gaps regarding the long-term stability of engineered rhizobiomes, the in situ dynamics of the Capsicum volatilome as a microbial recruitment signal, and the interactive effects of Cd contamination and drought in field environments. Overall, this synthesis provides a mechanistic framework for deploying high-pungency cultivars and microbiome-based strategies to improve Cd phytostabilisation, with important implications for sustainable chilli production in drought-prone, metal-contaminated agroecosystems. Full article

Background: Boundary-spanning bank employees experience continuous customer interactions that can generate negative emotions and influence how they perceive interpersonal treatment at work. Although emotions are known to shape fairness judgments, little is understood about how negative emotions translate into lower interactional justice through self-related psychological mechanisms. This study examines whether organization-based self-esteem (OBSE), self-efficacy, and external workplace locus of control (EWLOC) jointly condition the association between negative emotions and interactional justice. Method: Survey data were obtained from 338 boundary-spanning bank workers in Istanbul, Türkiye. The proposed moderated mediation framework was examined using PROCESS Macro Model 21, testing OBSE as a mediator between negative emotions and interactional justice. Self-efficacy and EWLOC were included as moderators on the first- and second-stage paths. Bootstrapping with 5000 resamples provided confidence intervals for the conditional indirect effects. Results: Stronger negative emotions were associated with lower OBSE and lower interactional justice perceptions, and the pattern of results was consistent with an indirect association via OBSE. The negative emotion–OBSE association varied by self-efficacy, with the association being stronger among employees reporting lower self-efficacy. EWLOC conditioned the OBSE–justice association, such that this association was weaker at higher levels of external orientation. The conditional indirect association was significant for employees low in self-efficacy and low-to-moderate in EWLOC. Conclusions: The findings are consistent with a moderated mediation model in which negative emotions are indirectly linked to interactional justice through OBSE, with the magnitude of these associations depending on employees’ personal resources and attributional tendencies. The results suggest that strengthening OBSE and related psychological resources may be useful for supporting justice perceptions in emotionally demanding service roles. Full article

Barley grown in temperate regions is often challenged by powdery mildew disease. An effective solution is mildew resistance locus o (mlo)-based resistance, which is monogenic, durable, and broad-spectrum. While the pleiotropic effects of mlo mutations on above-ground tissues are well documented, their impact on the root-associated microbiome remains underexplored. We utilized CRISPR/Cas9 to generate novel mlo mutant lines and evaluated their resistance to causal fungus Blumeria hordei. We further examined if mlo knockout has any impact on the overall root microbiome diversity and composition under field-like conditions and applied DESeq2 to compare the abundance of microbial taxa between mutants and wild type. We created five novel resistant mlo lines, including the first mutants with amino acid alterations in the protein’s extracellular region. Mutant lines showed significantly reduced B. hordei colony formation (0.5–5%). While microbial alpha and beta diversity were not significantly altered, a few microbial taxa displayed time-dependent shifts in abundance. Overall, our study demonstrates the effectiveness of CRISPR/Cas9 in generating mlo-based resistance. Moreover, the study revealed functionally important residues in the protein’s extracellular region. Finally, we present the first evidence of limited mlo-associated effects on root microbiome diversity and relative abundance of microbial taxa. Full article

Low temperature is a major abiotic stress that affects maize across its entire growth cycle, with the germination stage being particularly sensitive. To investigate the genetic basis of early-stage cold tolerance, we used quantitative trait locus mapping and identified ZmbHLH30 as a candidate gene regulating maize responses to low temperature. The ZmbHLH30 protein is localized in the cytoplasm of maize protoplasts, and ZmbHLH30 promoter drives β-glucuronidase (GUS) expression in Arabidopsis thaliana leaves. The promoter region of ZmbHLH30 contains multiple environmental stress-responsive elements, including motifs associated with cold and auxin responses. Overexpression of ZmbHLH30 significantly enhanced cold tolerance at the germination, bud, and seedling stages, with the strongest effect observed during germination, where the cold-tolerance D-value increased by 0.366 relative to the control. In contrast, CRISPR/Cas9 knockout lines showed a 0.399 decrease in D-value. Under cold stress, ZmbHLH30 expression was markedly induced in overexpression lines but suppressed in knockout lines. Integrated transcriptomic and metabolomic analyses further identified ZmbHLH30 as a key regulator of cold tolerance in maize. Full article

This study aimed to characterize the site-specific variation in skin traits of Shenxian pigs and to identify key genetic loci regulating skin thickness. A total of 50 Shenxian pigs were selected, and skin samples were collected from nine different anatomical sites. Total skin thickness was precisely measured, and collagen content was determined for each site. Based on literature review and database screening, TAF11 was identified as a candidate gene. Genotyping of the g.35543837 locus was performed using Sanger sequencing and KASP, followed by association analysis between different genotypes and skin thickness traits. The results showed significant site-specific variations in skin thickness (1.26–7.20 mm) and collagen content (7.01–24.54 g/100 g) in Shenxian pigs. Association analysis revealed that the TAF11 g.35543837 C > G variant was significantly associated with increased skin thickness, with the effect being particularly evident in gilt. Individuals with the CG genotype exhibited greater skin thickness at multiple anatomical sites compared with those carrying the CC genotype. This study preliminarily identified a potential locus associated with skin thickness in Shenxian pigs within the TAF11 gene. The sex-dependent effect observed at this locus provides a new clue for understanding the genetic basis of this complex trait and offers valuable information for the genetic improvement of skin-related traits in Shenxian pigs. Full article

Stem lodging critically limits wheat yield stability, with its resistance heavily influenced by internode mechanical strength, a trait whose genetic architecture remains poorly resolved. This study aimed to dissect the genetic basis of stem strength in the first three basal internodes of wheat. Using a panel of 224 cultivars, we measured internode strength across two environments and performed a genome-wide association study with 269,708 SNPs, employing the FarmCPU model. Three stable quantitative trait loci (QTL) associated with internode stem strength were identified: QI1SS.sau.5A, QI2SS.sau.2D, and QI2SS.sau.6B across a diverse wheat panel, with allele-dependent effects observed among accessions. Among them, QI2SS.sau.2D consistently enhanced stem strength across all three internodes, explaining up to 10.8% of phenotypic variance, without adverse effects on plant height or thousand-grain weight. In contrast, the other two QTL were associated with trade-offs, such as reduced plant height or grain weight. These results reveal a polygenic and partially internode-shared genetic regulation of stem strength. The locus QI2SS.sau.2D is highlighted as a particularly promising, penalty-free target for marker-assisted selection to improve lodging resistance while maintaining agronomic performance, including plant height and thousand-grain weight. Full article

Background/Objectives: Females are generally more resistant to ischemia-related ferroptosis than males, due to differences in iron metabolism, antioxidant pathways, and sex hormone-mediated regulation of ferroptosis suppressors. This has not been systematically studied in a human donor liver model. To investigate the effect of sex on ferroptosis and oxidative stress pathways in non-utilized donor livers (NDLs), we assessed patterns of gene expression in NDLs under ex vivo normothermic machine perfusion (NMP). Methods: We utilized the PROTECT dual-circuit ex vivo NMP system to assess three male and two female NDLs undergoing 6 h NMP. Perfusate and tissue samples were collected at baseline and 6 h of NMP. Malondialdehyde (MDA) levels were quantified as biochemical markers of iron overload and lipid peroxidation, respectively. Ferroptosis-related gene expression was assessed using molecular assays. Comparisons between male and female NDLs were used to determine the influence of sex on ferroptosis and oxidative injury during NMP. Results: NMP was successfully performed on NDLs (n = 5) from three male (56.3 ± 5.7 years) and two female donors (46.5 ± 0.7 years, p = 0.15). The fold-change in the oxidative stress marker MDA was comparable between female (1.2 ± 0.6) and male (1.0 ± 0.4) NDLs after 6 h NMP (p = 0.76). All livers showed upregulation of ferroptosis-related genes (Hypoxia-inducible factor 1 alpha, Iron Responsive Binding Elements 2, Ribosomal Protein L8, Ferritin Heavy Chain 1, Acyl-CoA synthetase family member 2, ATP synthase membrane subunit c locus 3, Heme-oxygenase 1, NAD(P)H Quinone Dehydrogenase 1, Tetratricopeptide Repeat Domain 35, Nuclear Factor Erythroid 2 Related Factor 2). ACSF2 expression was significantly higher in female NDLs compared with males undergoing 6 h NMP (3.6 ± 3.0 vs. 1.0 ± 0.7-fold change, p = 0.04). There were no sex-based significant differences observed in the expression of other ferroptosis-related genes (HIF-1α, IREB2, RPL8, FTH-1, ATP5G3, HO-1, NQO1, TTC35, and NRF2) between male and female NDLs. No gene reached statistical significance after false-discovery-rate (FDR) correction. Conclusions: Normothermic machine perfusion of NDLs was feasible, and no sex-related differences were observed in MDA levels or most ferroptosis-related gene expression after 6 h. Although ACSF2 showed higher expression in female livers, this was not significant after multiple testing correction, highlighting the need for larger studies to explore sex-dependent ferroptosis signaling during liver preservation. Full article

Background: Diabetes mellitus is characterized by elevated blood sugar due to absolute or relative insulin deficiency. Diabetes is classified as type 1 (T1D) or type 2 diabetes (T2D), gestational diabetes, and other types, such as monogenic diabetes, exocrine pancreatic disorders, and medication-induced diabetes. Objectives: This review article provides an overview of diabetes genetics, covering polygenic, monogenic, and syndromic forms of the disorder with emphasis on aspects to help clinicians in diagnosis, management, and counseling, but also to foster valuable knowledge for diabetic researchers in identifying phenotypes that will help inform gene discovery. Key Findings: Most cases of T1D and T2D are polygenic with environmental triggers. T1D results from autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency. Genetic studies of T1D have focused on the identification of loci associated with increased susceptibility to T1D. Early studies showed a linkage between T1D and several human leukocyte antigen (HLA) susceptibility loci on chromosome 6. Genome-wide association studies (GWAS) have identified more than 100 HLA- and non-HLA loci that increase susceptibility to T1D. It has been well established that a substantial portion of the genetic risk for T1D is encoded in the HLA locus. The non-HLA loci INS, CTLA4, IL2RA, IFIH1, and PTPN22 make moderate contributions to T1D risk. Many other non-HLA loci have small effects to the phenotype and are relevant to autoimmunity, but they are yet to be identified. T2D, on the other hand, is associated with obesity and insulin resistance with relative insulin deficiency. Thousands of gene variants that are common and contribute small effects have also been identified through GWAS to contribute to T2D risk, but the rarer variants may confer significant risk to an individual’s risk. Common variants in the TCF7L2 locus consistently carry one of the largest risks associated with T2D with a reported 1.7-fold disease odds for homozygous carriers. The usefulness of individual variants for genetic counseling in the common forms of diabetes has been limited in clinical settings in the past. The development of polygenic risk scores (PRS) and partitioned polygenic risk scores (PPRS), statistics derived from GWAS, are being used to predict and classify diabetes. The performance of PRS and PPRS varies by ancestry and type of diabetes. The PRS performs better with T1D, with an area under the curve and receiver operating characteristics (AUC-ROC) ranging from 0.87 to 0.93, compared to 0.72–0.75 for T2D. The genetic architecture of T2D is markedly more polygenic than T1D, and the PPRS has been useful in assessing risk in that setting. Monogenic diabetes comprises several dysglycemic disorders that include neonatal diabetes, maturity-onset diabetes of the young (MODY), and other genetic syndromes that have diabetes either as an associated finding and/or as a complication. Some of the monogenic diabetes gene variants have incomplete penetrance and variable expressivity leading to different ages of onset and variable presentation even within the same family. Hence some patients with these conditions have been previously diagnosed as having T1D or T2D. Many monogenic disorders follow Mendelian inheritance patterns, so genetic counseling is relatively straightforward if pathogenic variants are found to be inherited from a parent. Counseling for forms of diabetes due to maternally inherited mitochondrial cytopathies, such as MELAS and Kearns–Sayres syndrome, is not straightforward due to the occurrence of two or more populations of genetically distinct mitochondrial DNAs in the cells (heteroplasmy); the higher the percent of pathogenic variants in a cell or tissue, the greater the chance for affectation of disorder. Implications: Early stages of diabetes may be asymptomatic, and improvement in methodologies to identify individuals at high risk is important so prevention strategies can be targeted to susceptible individuals to slow or obviate the onset of disease and to minimize complications. Conclusions: Diabetes is a heterogeneous disorder, and accurate definition of phenotypes in the setting of non-syndromic and syndromic forms, development of powerful statistical methodologies, use of next-generation sequencing applications to interrogate the genome, incorporation of epigenetic mechanisms in statistical modeling and accurate curation of gene variants, will help us to realize application of genomic medicine and to inform diabetes care. Full article

Prior research has offered substantial evidence for letter transposition effect in word reading, yet studies in logographic languages such as Chinese are scarce and have largely focused on adults. This study aimed to determine whether second-grade children show character transposition effect impact in recognizing two-character Chinese words and to examine potential differences between the left and right visual fields corresponding to the two cerebral hemispheres. A lexical decision task was used across two experiments. Experiment 1 tested 56 second graders and manipulated three stimulus types—normal words, Transposed pseudo-words, and Substituted pseudo-words—to verify the presence of the effect. Experiment 2 recruited an independent sample of 97 second graders and applied a lateralized presentation paradigm, presenting stimuli to either the right or left visual field (RVF/LVF), which project to the left and right hemispheres (LH/RH), respectively, to assess hemispheric differences. Experiment 1 revealed a significant character transposition effect among second-grade children. Experiment 2 showed no significant differences in the magnitude of the effect between the two visual fields. These findings provide new developmental evidence for Chinese word reading and important implications for theories of position encoding. Future studies should trace its developmental trajectory across a wider age range and diverse learning contexts. Full article

The LPIN1 rs13412852 variant has been linked to lipid levels and liver disease in children. This genotype may modulate the liver’s response to sedentary behaviour, potentially increasing the vulnerability of certain individuals to liver dysfunction. These findings underscore the need to consider both genetic predisposition and environmental exposures when evaluating disease risk. This study aims to investigate the association between the LPIN rs13412852 T-allele and sedentary behaviour and to explore how the interplay between genetic and environmental factors may contribute to individual susceptibility to liver-related conditions. rs13412852 was genotyped in a cohort from Southern Italy (n = 394), and all participants were administered an International Physical Activity Questionnaire (IPAQ), collected a blood sample, and underwent an abdominal ultrasound analysis. The association between metabolic dysfunction-associated steatotic liver disease (MASLD), rs13412852, and sedentary behaviour, alone and together with interaction, was studied. The results indicated a statistical association on MASLD, of rs13412852, and sedentary levels (OR = 1.80, 1.06 to 3.05 95% C.I., p = 0.03, and OR = 1.72, 1.13 to 2.64 95% C.I.), respectively, and also with interaction between moderate or sever sedentary level and T-carrier (OR = 2.99, 1.39 to 6.45 95% C.I., p = 0.005) adjusted for some covariates. The risk of MASLD was highest among individuals with both moderate/severe sedentary behaviour and the CT/TT genotype, suggesting a potential synergistic effect. These findings establish LPIN1 as both a physiological gatekeeper and a genetic susceptibility locus, with its influence subject to modification via behavioural treatments. Full article