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Organoids have emerged as powerful in vitro models that bridge the gap between traditional two-dimensional cultures and in vivo studies. Over the past decade, advances in stem cell biology and extracellular matrix (ECM) engineering have enabled the establishment of organoids that partially recapitulate the structural and functional features of the mammary gland. These models have provided new opportunities to investigate mammary development, lactation biology, and breast cancer. In this review, we summarize recent progress in the establishment of mammary organoids across species, including humans, mice, and livestock. We discuss the effects of cell source, ECM, and growth factors on organoid culture. We further highlight the applications of organoid culture in mammary gland development, lactation biology, drug screening, precision medicine, and cell-based milk production. Despite the large advances achieved in the technique, the current mammary organoid culture still has many limitations due to the incomplete understanding of tissue complexity, insufficient vascularization, loss of microenvironmental interactions, and challenges in reproducibility. Emerging strategies, such as multi-organ systems, three-dimensional bioprinting, and organoids-on-a-chip, offer promising approaches to improve the physiological relevance of this technique and functional maturity. Overall, mammary organoids represent a rapidly evolving platform with broad applications. They are expected to become important platforms linking mammary biology to livestock production and next-generation dairy biomanufacturing.
Blackgrass is a highly competitive weed in wheat fields and has increasingly evolved resistance to acetolactate synthase (ALS)-inhibiting herbicides. Ten field populations were screened, resulting in the selection of one highly resistant population (R-06) and one susceptible population (S-19) for detailed study. Whole-plant bioassays, ALS gene sequencing, molecular docking, metabolic inhibitor assays, glutathione S-transferase (GST) and ALS activity assays, and cross-resistance profiling were conducted to dissect the mechanisms of resistance. ALS sequencing identified three amino acid substitutions in R-06: Pro232Thr (P232T), His363Lys (H363K), and Trp574Leu (W574L). While W574L is a well-characterized ALS resistance-conferring mutation, P232T and H363K are outside major resistance hotspots and may serve secondary or compensatory roles. Molecular docking analyses predicted altered binding of mesosulfuron-methyl in the mutant ALS model, consistent with structural changes in the binding pocket. Metabolic inhibitor assays using malathion, piperonyl butoxide (PBO), and NBD-Cl resulted in modest increases in herbicide sensitivity, with a maximum reduction factor of 2.95 for PBO. GST activity was higher in R-06 at a single sampling time point (3 DAT). In addition, R-06 showed reduced sensitivity to several ALS inhibitors and reduced efficacy against selected herbicides with alternative modes of action. High-level resistance to mesosulfuron-methyl in the R-06 population is primarily associated with the ALS target-site mutation Trp574Leu, while the roles of Pro232Thr, His363Lys, and metabolism appear secondary and remain unresolved. These findings highlight complex resistance patterns in blackgrass and emphasize the need for diversified and integrated weed management strategies.
With the evolution from 5G to 6G and the popularization of carrier aggregation technology, mobile terminal devices face challenges in miniaturizing multiplexers and handling concurrent signals across a wide-bandgap. This study proposes a numerical de-embedding design method. By precisely calculating and compensating for the parasitic loads, it achieves deterministic synthesis of matching networks. Based on this method, we designed and fabricated a monolithic integrated surface acoustic wave triplexer on a lithium tantalite on insulator (LTOI) substrate for dual-frequency GPS L1/L5 positioning and Bluetooth (BT) communication. To suppress a specific spurious mode on the LTOI substrate and improve the isolation, a notch inductor structure was embedded into the design. The monolithic integrated triplexer measures 2.5 mm × 2.0 mm × 0.6 mm after packaging. The insertion loss is less than 1.6 dB in both the L1 and L5 bands. In the BT band, the average loss within any 18 MHz range of the passband is below 2.5 dB. The return loss for all three channels is better than −10 dB, while the isolation between channels is maintained at ≈40 dB. The successful fabrication of this triplexer not only validates the design method but also demonstrates its potential for application in miniaturized wearable devices.
While studies based on the civic voluntarism model generally suggest that stronger party identification increases electoral participation, other studies report mixed findings on the relationship between partisan strength and voter turnout. This study argues that the participatory effect of party identification depends on whether voters’ partisan identity is consistent with the party affiliation of their preferred candidate. Drawing on conflicted voter theory, we argue that when voters identify with one party but prefer a candidate nominated by another party, the psychological costs generated by betrayal aversion reduce their likelihood of voting. Using pooled survey data from the Taiwan Election and Democratization Study (TEDS) for Taiwan’s presidential elections from 2008 to 2024, our binary logistic regression results support this argument. This study contributes to the literature by showing that conflicted voter status should be incorporated into future studies of voter turnout. It also suggests that political parties should pay closer attention to conflicted voters in closely contested elections, because turnout differences within a small segment of the electorate can have notable political consequences.
Few studies have quantitatively characterised the shared and distinct features of the epigenetic age signature of schizophrenia, bipolar disorder and major depressive disorder.
Aims
To construct a multi-platform epigenetic clock tailored to human blood and brain tissues, and to characterise variations in epigenetic age acceleration across these three common psychiatric disorders.
Method
We integrated 31 publicly available DNA methylation data-sets generated on the platforms Illumina 27K, 450K and EPIC (850K) from patients with schizophrenia, bipolar disorder or major depressive disorder, and from matched controls. Using elastic net regression combined with sure independence screening, we developed the blood–brain clock and applied it to assess disorder-specific epigenetic age acceleration in blood and brain.
Results
The blood–brain clock achieved high accuracy across tissues and outperformed established predictors, particularly in brain samples. Epigenetic age acceleration was reduced in schizophrenia, increased in bipolar disorder and major depressive disorder and strongly elevated in Alzheimer’s disease (positive control). Alterations appeared earlier in blood than in brain. Meta-analysis confirmed that both reduced acceleration (schizophrenia) and increased acceleration (bipolar disorder, major depressive disorder, Alzheimer’s disease) were significantly associated with disease prevalence. Differential methylation analyses further revealed that the blood–brain clock probes captured disease-associated signals, with schizophrenia showing the greatest overlap with causal risk loci, and opposite methylation patterns distinguishing schizophrenia from bipolar disorder or major depressive disorder. A subset of blood DNA methylation probes enabled high-precision classification between schizophrenia and bipolar disorder or major depressive disorder.
Conclusions
This blood–brain clock reveals distinct patterns of epigenetic age acceleration across psychiatric disorders, reflecting disorder-specific and shared biological ageing signatures. The manifestation of these alterations in peripheral blood highlights its potential as a non-invasive biomarker for early detection, risk stratification and differential classification of schizophrenia, bipolar disorder and major depressive disorder.
Irritable bowel syndrome (IBS) commonly co-occurs with psychological distress, including depression and anxiety, but the temporal and bidirectional nature of this relationship remains unclear. Dysregulation of the gut–brain–microbiota axis has been proposed as a shared mechanism.
Methods
We conducted two retrospective, population-based cohort studies using Taiwan’s National Health Insurance Research Database (2000–2015). Cohort 1 assessed the risk of incident IBS among patients with newly diagnosed depression or anxiety, while Cohort 2 evaluated the risk of subsequent depression or anxiety among patients with newly diagnosed IBS. Propensity score matching, multivariable Cox regression, and Fine–Gray competing risk models were applied.
Results
IBS was associated with increased risks of depression (adjusted hazard ratio [aHR] = 1.55) and anxiety (aHR = 1.68). Conversely, depression and anxiety were associated with higher risks of developing IBS (aHR = 1.45 and 1.51, respectively). Associations were stronger among females and younger adults aged 18–39 years. Sleep disorders (SDs) showed the strongest modifying effect in both directions (sub-distribution HR ≈ 1.60). Results were consistent across sensitivity analyses.
Conclusions
This nationwide longitudinal study demonstrates a robust bidirectional association between IBS and psychological distress, supporting integrated screening and multidisciplinary care approaches targeting gut–brain interactions.
While mobile gaming addiction (MGA) behavior is increasingly prevalent among children and adolescents, the role of specific emotional-behavioral profiles – particularly their latent patterns – in associating with MGA behavior remains poorly understood. This study aimed to examine these associations and age-related variations.
Methods
Data were analyzed from 507,188 participants aged 6–18 years in the Children’s Growth Environment, Lifestyle, and Physical and Mental Health Development Project, conducted in Guangzhou, China, in 2020. Latent class analysis was performed on parent-reported Strengths and Difficulties Questionnaire (SDQ) data to identify subgroups with distinct emotional and behavioral problems. Associations between SDQ dimensions, latent classes, and MGA behavior were examined using logistic regression analysis.
Results
Five latent classes were identified: ‘Low symptom’ (82.2%), ‘Internalizing’ (0.8%), ‘Peer and prosocial issues’ (4.3%), ‘High difficulties’ (5.0%), and ‘Hyperactive’ (7.6%). Compared to the ‘Low symptom’ class, all other latent classes showed significantly higher risks for MGA, with the strongest association observed in the ‘Internalizing’ class (adjusted odds ratio [AOR]: 2.84; 95% confidence interval [95% CI]: 2.67–3.02). Among SDQ subscales, conduct problems presented the highest association (AOR: 2.08; 95% CI: 2.04–2.12), though all SDQ subdimensions were significantly positively correlated with MGA behavior (all p < 0.05). Notably, these associations were consistently stronger in adolescents (aged 13–18 years) than in children (aged 6–12 years).
Conclusions
This study identifies specific SDQ-based risk characteristics for MGA behavior, with adolescents (aged 13–18 years) being the most vulnerable. Future longitudinal studies should verify these associations, and clinicians may prioritize early screening for internalizing and conduct-related difficulties.
China accounts for over 90% of global alveolar echinococcosis (AE) cases caused primarily by Echinococcus multilocularis. If left untreated, AE can have a 10-year mortality rate of 94%. Understanding its epidemiological patterns is essential for targeted control strategies. Surveillance data from 2006 to 2020 were obtained from the Public Health Scientific Data Center, and spatial and temporal trends were analyzed using spatial autocorrelation, hot spot analysis, and centroid migration techniques. A total of 51,403 echinococcosis cases were reported from 2006 to 2020, with an average annual incidence of 0.25 per 100,000. Most cases (71.33%) occurred in individuals aged 20–60 years. High-incidence areas centred in western/northwestern provinces, including Qinghai, Xinjiang, Xizang, Gansu, and Ningxia. Incidence and cases increased until 2017, then declined steadily. Spatial autocorrelation revealed persistent High-High clusters in Gansu and Ningxia (2008–2018) and Xizang (2010–2020), while Low-Low clusters persisted in central/eastern China. Hotspot analysis confirmed sustained high-risk zones in western/northwestern regions. Trend surface and centroid migration showed a southward disease shift within Qinghai. Echinococcosis remains endemic in western/northwestern China, with a trend of southward expansion. Strengthened, tailored interventions are urgently needed, particularly in high-burden areas like Xizang and Qinghai.
Drug use among young women has severe consequences for their mental health, increases their developmental vulnerability and highlights the global problem of drug addiction. The purpose of this study was to investigate the socioeconomic and psychological factors influencing drug use among young women in Khyber Pakhtunkhwa, Pakistan. The study used a qualitative research design. We collected data from 12 women aged 18–21 years via in-depth qualitative interviews conducted in Mardan and Peshawar from March to June 2022. Research shows that young women frequently use drugs due to peer pressure, emotional challenges and financial concerns, which significantly impact their lives. The study emphasizes the value of cultural intervention programs for young women, concentrating on the region’s mental health services, economic empowerment and gender-specific peer support networks.
TNF-α polymorphisms may influence dyslipidaemia, but their role remains unclear. This case–control study investigated associations between TNF-α gene polymorphisms (–1031T/C, −863C/A, −857C/T, −308G/A and −238G/A) and dyslipidaemia in 595 participants (162 cases, 433 controls) from the Chaoshan region of China. Anthropometric, biochemical and genetic data were analysed using χ2 tests and logistic regression, with the false discovery rate (FDR) method applied to correct for multiple comparisons. Results revealed that only the −1031T/C and −863C/A polymorphisms were significantly associated with dyslipidaemia. Carriers of the TC + CC genotype for −1031T/C (OR = 0·48; 95 % CI: 0·30, 0·78; PFDR = 0·006) and the CA + AA genotype for −863C/A (OR = 0·41; 95 % CI: 0·24, 0·70; PFDR = 0·004) had lower odds of dyslipidaemia. Protective effects were observed for the C allele at −1031T/C (OR = 0·58, PFDR = 0·012) and the A allele at −863C/A (OR = 0·47, PFDR = 0·004). Stratified analyses showed that these associations were significant in males but not females. Functional annotation linked these TNF-α gene polymorphisms to transcription factors (e.g. HNF-1A, STAT1β) in the adipogenesis pathway. This study reveals genetic associations between TNF-α polymorphisms and dyslipidaemia, particularly in males, and provides mechanistic insights into their role in transcriptional regulation.
In this paper, by means of upper approximation operators in rough set theory, we study representations for sL-domains and its special subclasses. We introduce the concepts of sL-approximation spaces, L-approximation spaces, and bc-approximation spaces, which are special types of CF-approximation spaces. We prove that the collection of CF-closed sets in an sL-approximation space (resp., an L-approximation space, a bc-approximation space) ordered by set-theoretic inclusion is an sL-domain (resp., an L-domain, a bc-domain); conversely, every sL-domain (resp., L-domain, bc-domain) is order-isomorphic to the collection of CF-closed sets of an sL-approximation space (resp., an L-approximation space, a bc-approximation space). Consequently, we establish an equivalence between the category of sL-domains (resp., L-domains) with Scott continuous mappings and that of sL-approximation spaces (resp., L-approximation spaces) with CF-approximable relations.
The operational reliability of large mechanical equipment is typically influenced by the functional effectiveness of key components. Consequently, prompt repair before their failure is necessary to ensure the dependability of mechanical equipment. The prognostic and health management (PHM) technology could track the system’s health state and timely detect faults. Therefore, the remaining useful life (RUL) prediction as one of the key components of PHM is rather important. Accurate RUL prediction results could be the data support for condition-based equipment maintenance plans. Also, it could increase the dependability and safety of mechanical equipment while reducing the loss of human and financial resources and meet the requirements of sustainable manufacturing in the Industry 4.0 era. However, with the widespread use of deep learning in the field of intelligent manufacturing, there is a lack of review on RUL prediction based on deep learning. In this paper, different deep learning-based RUL prediction methods for mechanical components are summarized and classified, along with their pros and cons. Then, the case study on the C-MAPSS dataset is mainly conducted and different methods are compared. And finally, the difficulties and future directions of the RUL prediction in practical scenarios are discussed.
We demonstrated a method to improve the output performance of a Ti:sapphire laser in the long-wavelength low-gain region with an efficient stimulated Raman scattering process. By shifting the wavelength of the high-gain-band Ti:sapphire laser to the long-wavelength low-gain region, high-performance Stokes operation was achieved in the original long-wavelength low-gain region of the Ti:sapphire laser. With the fundamental wavelength tuning from 870 to 930 nm, first-order Stokes output exceeding 2.5 W was obtained at 930–1000 nm, which was significantly higher than that directly generated by the Ti:sapphire laser, accompanied by better beam quality, shorter pulse duration and narrower linewidth. Under the pump power of 42.1 W, a maximum first-order Stokes power of 3.24 W was obtained at 960 nm, with a conversion efficiency of 7.7%. Furthermore, self-mode-locked modulations of first- and second-order Stokes generation were observed in Ti:sapphire intracavity solid Raman lasers for the first time.
Rumen microbial biohydrogenation (RBH) is the major factor responsible for the bovine milk rich in saturated fatty acids (FAs). Here, we evaluated the effects of nutritional manipulation of ruminal propionogenesis and methanogenesis, two primary hydrogen sinks, on the RBH and milk FA profiles in vivo and in vitro using three propionogenesis enhancers (fumarate [FUM], biotin and monensin) and one methanogenesis inhibitor (N-[2-(nitrooxy)ethyl]-3-pyridinecarboxamide [NPD]). The in vivo results showed that inclusion of FUM in lactating dairy goat diet could protect dietary unsaturated FAs against RBH with increased proportions of C18:2n − 6 (by 33.5%), C18:3n − 3 (by 38.1%) and RBH intermediates (e.g. trans-10 C18:1 and trans-11 C18:1) in rumen contents. Additionally, FUM supplementation increased the milk Δ9 desaturase index (by 15.5%) with higher cis-9 monounsaturated FAs in the milk. As a result, FUM increased the proportions of polyunsaturated and monounsaturated FAs in the milk with lower atherogenicity index (by −15.3%) and thrombogenicity index (by −19.5%). Conversely, supplementing NPD increased RBH completeness (by 7.4%) with higher milk atherogenicity index (by 10.5%) and thrombogenicity index (by 8.7%). The adverse effects of NPD on the milk FA profiles can be eliminated when supplemented in combination with FUM. The metagenomic analyses showed that neither FUM nor NPD affect the rumen microbial α- or β-diversity at the strain or gene level. The in vitro study showed that the conversion rate of FUM to propionate was increased from 54.7% to 80.6% when FUM supplemented in combination with biotin and monensin, resulting a higher anti-RBH potential. Accordingly, manipulation of ruminal methanogenesis and propionogenesis can redirect hydrogen toward or away from RBH and thereby influence the milk FA profiles. FUM is a promising feed additive in ruminant not only to reduce the methane emissions as previously proved but also to improve the nutritional desirability of the milk FA profiles for human health.
Introduction: Late-life depression (LLD) is associated with cognitive deficit with risk of future dementia. By examining the entropy of the spontaneous brain activity, we aimed to understand the neural mechanism pertaining to cognitive decline in LLD.
Methods: We collected MRI scans in older adults with LLD (n = 32), mild cognitive impairment [MCI (n = 25)] and normal cognitive function [NC, (n = 47)]. Multiscale entropy analysis (MSE) was applied to resting-state fMRI data. Under the scale factor (tau) 1 and 2, reliable separation of fMRI data and noise was achieved. We calculated the brain entropy in 90 brain regions based on automated anatomical atlas (AAL). Due to exploratory nature of this study, we presented data of group-wise comparison in brain entropy between LLD vs. NC, MCI vs. NC, and LLD and MCD with a p-value below 0.001.
Results: The mean Mini-Mental State Examination (MMSE) score of LLD and MCI was 27.9 and 25.6. Under tau 2, we found higher brain entropy of LLD in left globus pallidus than MCI (p = 0.002) and NC (p = 0,009). Higher brain entropy of LLD than NC was also found in left frontal superior gyrus, left middle superior gyrus, left amygdala and left inferior parietal gyrus. The only brain region with higher brain entropy in MCI than control was left posterior cingulum (p-value = 0.015). Under tau 1, higher brain entropy was also found in LLD than in MCI in right orbital part of medial frontal gyrus and left globus pallidus (p-value = 0.007 and 0.005).
Conclusions: Our result is consistent with prior hypothesis where higher brain entropy was found during early aging process as compensation. We found such phenomenon particular in left globus pallidus in LLD, which could be served as a discriminative brain region. Being a key region in reward system, we hypothesis such region may be associated with apathy and with unique pathway of cognitive decline in LLD. We will undertake subsequent analysis longitudinally in this cohort
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
Purple nutsedge (Cyperus rotundus L.) is one of the world’s resilient upland weeds, primarily spreading through its tubers. Its emergence in rice (Oryza sativa L.) fields has been increasing, likely due to changing paddy-farming practices. This study aimed to investigate how C. rotundus, an upland weed, can withstand soil flooding and become a problematic weed in rice fields. The first comparative analysis focused on the survival and recovery characteristics of growing and mature tubers of C. rotundus exposed to soil-flooding conditions. Notably, mature tubers exhibited significant survival and recovery abilities in these environments. Based on this observation, further investigation was carried out to explore the morphological structure, nonstructural carbohydrates, and respiratory mechanisms of mature tubers in response to prolonged soil flooding. Over time, the mature tubers did not form aerenchyma but instead gradually accumulated lignified sclerenchymal fibers, with lignin content also increasing. After 90 d, the lignified sclerenchymal fibers and lignin contents were 4.0 and 1.1 times higher than those in the no soil-flooding treatment. Concurrently, soluble sugar content decreased while starch content increased, providing energy storage, and alcohol dehydrogenase activity rose to support anaerobic respiration via alcohol fermentation. These results indicated that mature tubers survived in soil-flooding conditions by adopting a low-oxygen quiescence strategy, which involves morphological adaptations through the development of lignified sclerenchymal fibers, increased starch reserves for energy storage, and enhanced anaerobic respiration. This mechanism likely underpins the flooding tolerance of mature C. rotundus tubers, allowing them to endure unfavorable conditions and subsequently germinate and grow once flooding subsides. This study provides a preliminary explanation of the mechanism by which mature tubers of C. rotundus from the upland areas confer flooding tolerance, shedding light on the reasons behind this weed’s increasing presence in rice fields.
NADPH-cytochrome P450 reductase (CPR) is crucial for the detoxification process catalysed by cytochrome P450, which targets various exogenous xenobiotics, as well as pesticides. In our research, we successfully obtained the complete cDNA sequence of Apolygus lucorum's CPR (AlCPR) using reverse transcription PCR along with rapid amplification of cDNA ends technology. Bioinformatics analysis exhibited that the inferred amino acid sequence of AlCPR is characteristic of standard CPRs, featuring an N-terminal membrane anchor and three conserved FMN, FAD and NADP binding sites. Phylogenetic result revealed that AlCPR was positioned within the Hemiptera cluster, showing a close evolutionary relationship with the CPR of Cimex lectularius. The real-time quantitative PCR results demonstrated widespread expression of AlCPR across various life stages and tissues of A. lucorum, with the most prominent expression in adults and the abdominal region. Injecting double-stranded RNA of AlCPR only significantly increased the lambda-cyhalothrin susceptibility in lambda-cyhalothrin-resistant strain rather than the susceptible strain. These findings suggest a potential link between AlCPR and the P450-dependent defence mechanism against lambda-cyhalothrin in A. lucorum.