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Dolomite, drainage, organic manure, and natural phosphate utilization to mitigate the effect of iron and sulfide toxicity on rice productivity in irrigated rice fields: case of Burkina Faso
No full textAbstract Rice cultivation in Burkina Faso faces major constraints from iron and sulfide toxicities that reduce rice productivity. This study investigated strategies to mitigate these stresses through improved drainage, fertilization, and variety selection across seasons. Field experiments were carried out in the Kou Valley during the dry and rainy seasons using a split-split plot in a Lattice design with three replications. Two rice varieties—FKR76 (iron-susceptible) and FKR62N (iron-tolerant)—were evaluated under two drainage regimes (D0: no drainage; D2: 14-day drainage) and eight fertilization treatments, including NPK + Urea (F2), NPK + Urea + Dolomite + Zn (F3), and NPK + Urea + Natural Phosphate (F4), each with (FO) or without (SFO) organic manure. Dolomite, organic matter, and natural phosphate were applied at rates of 200 kg·ha⁻¹, 15 t·ha⁻¹, and 250 kg·ha⁻¹, respectively. Results indicated significantly higher yields during the rainy season for both varieties (p < 0.05), with FKR62N producing 2730 g·plot⁻¹ and FKR76 2115 g·plot⁻¹ under FOF3 and FOF4 treatments. In the dry season, FKR76 showed significant differences in yield (1206.87 g·plot⁻¹), tiller number (107.85), and panicle number (92.58), whereas for FKR62N, only panicle number varied significantly, for all treatments combined. Drainage improved yield and panicle formation for FKR62N but had a limited impact on FKR76. Overall, integrating tolerant rice varieties with periodic drainage and fertilization using FOF3 or FOF4 appears promising for improving yields in iron- and sulfide-toxic soils. Although FOF3 favored FKR62N and FOF4 performed better for FKR76, these effects were not fully consistent across seasons. Multi-season and multi-site studies are therefore required to validate these trends and ensure the robustness of the proposed fertilization strategies
Translational applicability of human blood-brain barrier spheroid models for the development of brain-penetrant therapeutic antibodies
No full textAbstract Drug delivery systems play a key role in the development of new therapeutic strategies for brain diseases. Antibodies capable of crossing the blood–brain barrier (BBB) have attracted considerable attention as promising drug carriers. To facilitate their development, we previously established human multi-cellular spheroidal (hMCS)-BBB models as microphysiological system-based platforms. In this study, we aimed to enhance the applicability of these hMCS-BBB models for the development of brain-permeable antibodies using four anti-human transferrin receptor monoclonal antibodies (hTfRMAbs). Permeability assays using hMCS-BBB models revealed BBB permeability in three out of four hTfRMAbs, with two antibodies exhibiting Km values of 6.5 and 12.0 µg/mL, respectively. Importantly, differences in the BBB permeability of tested hTfRMAbs were consistent with the brain permeability profiles reported in monkeys in vivo. Moreover, these differences were not detected via simple uptake assays using monoculture brain microvascular endothelial cells, highlighting the superior evaluation potential of hMCS-BBB models. Lysosome co-localization assays using hMCS-BBB models revealed the distinct intracellular localization patterns of BBB-permeable and non-permeable hTfRMAbs with lysosomes, presumably explaining their different permeability properties. Overall, hMCS-BBB models effectively characterized the BBB permeability of hTfRMAbs, demonstrated strong potential for in vivo extrapolation, and proved suitable for mechanistic studies of the cellular pathways regulating their BBB permeability. Therefore, hMCS-BBB models are considered promising tools for advancing the development of brain-permeable therapeutic antibodies. Graphical Abstrac
Beyond household meals: a game-based approach to unveiling the role of insects in Malagasy children’s diets
No full textAbstract Background Insects have long been an integral part of Malagasy cuisine; however, their role in children’s lives outside traditional household contexts remains overlooked. This study examined the non-familial collection and consumption of edible insects among Malagasy children aged 6 to 15 years in rural communities of the Analamanga region in central Madagascar. Methods Using two different assessment methods, direct questioning with adults and a game-based approach with children, we investigated children’s activities with edible insects during play. The findings revealed important differences between the two methods. Ethical compliance was confirmed by the institutional committee, which reviewed and approved the study design prior to data collection. Results Adults identified eight insect species consumed by children while playing, whereas children themselves reported consuming eleven species, suggesting that direct questioning may overlook certain aspects of children’s diets. The game-based approach proved to be a more effective tool in revealing hidden consumption patterns, as it allowed children to naturally show their interactions with insects. Overall, 35% of children’s games involved insects, with 71% of these games leading to consumption. On average, children consumed insects while playing three times a week, in addition to any insect intake during household meals, indicating a separate pathway of entomophagy. The most commonly consumed species include beetles such as Voangory (Scarabaeidae: Melolonthinae) and Voanosy (Curculionidae: Polycleis Marshall, 1916), which are often collected during the rainy season, a period of food scarcity. Conclusions The findings highlight the importance of alternative, child-centered methods for studying food consumption practices. Game-based observation can reveal informal eating practices that are invisible to adult-reported surveys. These results confirm the nutritional and cultural significance of edible insects in Madagascar, highlight the surprisingly frequent consumption of insects outside formal meal contexts by children, and reveal overlooked pathways relevant to food security
“I know a lot about medicinal plants. I read, I watch, and I search": towards hybrid knowledge systems in the modern era
No full textAbstract Background Hybrid knowledge systems are central to community negotiations of environmental, social, and epistemic pressures. In multilingual borderland areas, interactions between local ecological knowledge (LEK), formal, and popular knowledge systems remain underexplored, despite their importance for the persistence and transformation of medicinal plant use today. Methods We conducted 67 semi-structured interviews and participant observation in 21 rural settlements of the Vilnius region (Lithuania), an area bordering Belarus, focusing on the two largest local groups, Lithuanians (LT) and Poles (PL). Detailed Use Reports (n = 1446) on medicinal plant use were coded by the origin of knowledge, classified as local, formal, or popular, and the degree of hybridisation was quantified using the Shannon–Wiener diversity index and hybridisation metrics. Sociodemographic variables (age, gender, education, and multilingualism) were tested for associations with hybridisation using Spearman’s ρ and Student’s t-tests. Results A total of 139 medicinal taxa were recorded, of which 68 (49%) were shared between the two groups. Overall, recorded medicinal plant knowledge remained primarily grounded in LEK, sustained through intergenerational transmission. Compared with PL, LT interviewees drew on a broader mix of knowledge-origin domains (H′ = 0.97 vs 0.52) and combined them more often (HD = 0.195 vs 0.059). In total, 39 taxa showed hybrid use, predominantly in the LT group. Hybridisation was negatively associated with age but positively correlated with the number of listed plants and their reported uses, while multilingualism showed a near-significant positive trend. Conclusions The study suggests that medicinal plant knowledge has evolved here through hybridisation, a process whose consequences are context-dependent, offering opportunities for revitalisation but also a risk of displacement. Dialogic exchanges across families, communities, languages, and media expand people’s plant repertoire and strengthen community adaptive capacity. Yet when these exchanges lead to excessive standardisation, they risk eroding the diversity of local traditions. Ethnobotanical research must therefore go beyond documenting popular and formal knowledge sources to interrogate how linguistic and sociopolitical contexts condition the emergence of hybrid knowledge systems, privileging certain forms while rendering others transformed or marginalised
Fetal reversion from diverse lineages sustains the intestinal stem cell pool and confers stress resilience
No full textAbstract Plasticity is a central mechanism underlying the robust regenerative capacity of the intestinal epithelium. Two major forms of plasticity have been described: spatial plasticity, in which differentiated cells revert to crypt base columnar cells (CBCs), and fetal reversion into revival stem cells (revSCs). However, the relationship among these two stem cell populations and differentiated cells remains to be clarified. Here, we demonstrated the bidirectional interconversion between CBCs and revSCs. Using lineage tracing, injury models and villus culture, we show that absorptive enterocytes can reprogram into revSCs and regenerate CBCs. These findings position fetal reversion as an entry point to spatial plasticity, establishing a regenerative hierarchy where CBCs, revSCs, and enterocytes collectively orchestrate intestinal repair. Furthermore, we identified revSCs as a highly stress-tolerant stem cell population, whose emergence would preserve the stem cell pool. Our results establish fetal reversion as a cellular escape mechanism safeguarding epithelial regeneration under inflammatory conditions
Glycophagy is an ancient bilaterian pathway supporting metabolic adaptation through STBD1 structural evolution
No full textAbstract Glycophagy, a selective form of autophagy critical for glycogen homeostasis, relies on the glycogen cargo receptor called starch-binding domain-containing protein 1 (STBD1), yet its evolutionary origins remain elusive. Here, we provide evidence that the Pacific oyster Crassostrea gigas utilizes glycophagy to manage glycogen mobilization during periods of energy deprivation. We identify an oyster STBD1 protein, and trace its origins through phylogenetic and comparative genomic analysis of the carbohydrate binding module family 20 (CBM20) domain within this protein across metazoans. Oyster STBD1 and those in other invertebrates contain an N-terminal CBM20, contrasting the C-terminal location of CBM20 in vertebrate STBD1. N-terminal CBM20 STBD1 proteins have a deep origin in bilaterians, with the vertebrate structural arrangement arising at the chordate root. Structural modelling and functional studies reveal that the N-terminal organization of the CBM20 domain in STBD1 enhances glycogen binding, with subsequent anchoring by GABARAPL2, facilitating an increased glycogen flux into autophagosomes for lysosomal degradation. We conclude that glycophagy is deeply conserved in bilaterians and that STBD1 structural evolution underlies potentially adaptive variation in metabolic strategies across distinct animal clades
Targeting PAK4 promotes Gemcitabine-induced pyroptosis in pancreatic cancer via NLRP1/caspase-3/GSDME axis
No full textAbstract Pancreatic cancer remains a highly lethal disease, underscoring the continued importance of chemotherapy. The first-line chemotherapeutic agent Gemcitabine (GEM) exerts its effect by inducing tumor cell apoptosis, a process which can subsequently convert to pyroptosis via GSDME expression. Nevertheless, the emergence of drug resistance has prompted extensive research to identify novel therapeutic targets. p21-activated kinase 4 (PAK4) plays important roles in various tumors, including the inhibition of tumor cell apoptosis. Here, we show that PAK4 inhibits pyroptosis in pancreatic cancer through the NAcht leucinerich-repeat protein-1 (NLRP1)/caspase-9/caspase-3/GSDME axis. PAK4 phosphorylates the E3 ubiquitin ligase mouse double minute 2 homolog (Mdm2) to promote the degradation of NLRP1, thereby inhibiting pyroptosis. Furthermore, inhibition of PAK4 kinase activity promotes GEM-induced suppression of pancreatic cancer growth both in vitro and in vivo. Our study suggests that targeting PAK4 to promote GEM-induced pyroptosis may provide a new therapeutic approach for the treatment of pancreatic cancer
A deep learning radiopathomic signature predicts recurrence risk of hepatocellular carcinoma after hepatectomy
No full textAbstract Accurate prediction of recurrence risk after hepatectomy still remains a clinical challenge for hepatocellular carcinoma (HCC). We develop a deep learning radiopathomic (DLRP) signature to fuse deep features of CT images and histological whole-slide-image, aiming to predict the recurrence-free survival (RFS) in HCC patients. The multi-omics data in The Cancer Genome Atlas (TCGA) database are used to assess the potential biological interpretation. A total of 599 patients are enrolled in this study and divided into the training (n = 272), internal test (n = 120), external test (n = 174), and TCGA (n = 33) cohorts. The DLRP signature shows better prediction for RFS than radiomics signature, pathomics signature, clinical model, and Barcelona Clinic Liver Cancer stage in the external test cohort (C-index, 0.799 vs 0.541–0.738; P value range, <0.001–0.042). Patients in the high-risk group show worse RFS and overall survival in three cohorts than those in the low-risk group (all P < 0.001). The multi-omics data indicate that DLRP signature is relevant to Wnt/β-catenin signaling pathway and tumor immune infiltration. We conclude that the DLRP signature can efficiently predict recurrence risk in HCC patients, thereby facilitating personalized precision therapy
Publisher Correction: Hepatic organic anion transporting polypeptides (OATPs) as MRI reporter proteins
No full textCathelicidin CATH-2 suppresses the NF-κB/ROS/NLRP3 signaling pathway via regulating mTOR-dependent autophagy during Streptococcus suis infection
No full textAbstract Cathelicidin CATH-2 has been reported to exert potent anti-inflammatory activity in different species though neutralizing stimuli such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA). CATH-2 has been shown to inhibit Streptococcus suis (S. suis)-induced activation of dendritic cells and macrophages by binding to LTA. However, the exact mechanism of this prophylactically anti-inflammatory activity remains unclear. Therefore, we investigated the anti-inflammatory activity and mechanism of CATH-2 in mice peritoneal macrophages pretreated with CATH-2 followed by S. suis infection. The results showed that CATH-2 pretreatment significantly reduced S. suis-induced transcription and secretion of interleukin (IL)-1β, IL-6, and IL-12. CATH-2 also downregulated NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) expression and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, and inhibited the maturation of IL-1β, suggesting that CATH-2 inhibits NLRP3 activation. In addition, CATH-2 significantly inhibited S. suis-induced phosphorylation of p65 and extracellular signal-regulated kinase (ERK). Further study showed that CATH-2 inhibited S. suis-induced reactive oxygen species (ROS) by upregulating the expression of ROS scavenging genes including catalase (CAT) and superoxide dismutase 1 (SOD1). Mechanistically, transcriptome analysis revealed that CATH-2 regulated the protein kinase B (ATK)/mammalian target of rapamycin (mTOR) pathway, which was evident by the downregulation of phosphorylated (p)-ATK and p-mTOR induced by CATH-2. Notably, CATH-2 induced autophagy and autophagic flux. Inhibition of mTOR using rapamycin enhanced the CATH-2-induced autophagic efficacy, demonstrating that CATH-2 induces mTOR-dependent autophagy. However, inhibition of autophagy using 3-methyladenine (3-MA) reversed the reduction in the expression of p-p65, p-ERK, and IL-1β induced by CATH-2. Our study reveals that CATH-2 inhibits the nuclear factor kappa-B (NF-κB)/NLRP3-mediated inflammatory response through the induction of mTOR-dependent autophagy during S. suis infection, which provides new insight into the anti-inflammatory pathways of antimicrobial peptides
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