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Children with autism spectrum disorder (ASD) frequently exhibit selective eating behaviors characterized by food refusal and limited dietary variety, which can lead to nutritional deficiencies and impaired family functioning. This study evaluated the effectiveness of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a creative behavioral intervention integrating established behavioral strategies with innovative components, including imitation chaining, shaping, and therapist-guided exoskeleton modeling. Three children (YW, RA, and JK) diagnosed with autism spectrum disorder (ASD) participated in a single-case experimental design. The study employed the Childhood Autism Rating Scale, 2nd Edition (CARS-2) assessing autism symptom severity, while the Child Eating Behavior Questionnaire (CEBQ) measured changes in eating behavior. Substantial increases in food acceptance were observed across all participants, with the highest improvements in food responsiveness, enjoyment of food, and food fussiness. Tau-U analysis revealed large and significant intervention effects for both therapist-implemented and parent-implemented sessions. Although CARS-2 scores remained within the 'severe' classification range, notable percentage reductions suggested clinically relevant improvements in core autism symptoms. These findings support the Schmetterling NBI Program as an individualized, evidence-based approach to enhancing dietary diversity and reducing maladaptive feeding behaviors in children with ASD. Children with autism spectrum disorder (ASD) commonly demonstrate selective eating patterns, including food refusal and restricted dietary repertoire, which may contribute to nutritional deficits and compromised family dynamics. This investigation examined the efficacy of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a novel behavioral intervention that synthesizes established behavioral methodologies with innovative components such as imitation, shaping procedures, and therapist-guided training. Utilizing a single-case experimental design, three children diagnosed with ASD (YW, RA, and JK) were assessed with the Childhood Autism Rating Scale, Second Edition (CARS-2) to evaluate autism symptom severity, and the Child Eating Behavior Questionnaire (CEBQ) to measure alterations in feeding behavior. Results indicated substantial improvements in food acceptance across all participants, with pronounced enhancements in food responsiveness, enjoyment of food, and reductions in food fussiness. Tau-U statistical analysis demonstrated large and significant intervention effects for both therapist-administered and parent-implemented sessions. Although CARS-2 scores remained within the severe classification range, notable percentage reductions indicated clinically meaningful improvements in core autism symptomatology. These findings support the Schmetterling NBI Program as an individualized, evidence-based intervention for promoting dietary diversity and reducing maladaptive feeding behavior among children with ASD. Replicating our preliminary findings in a larger sample and finding evidence-based tailored interventions for children with ASD pose important challenges for future research.

The role of diet in multiple sclerosis (MS) development is still a matter of debate and its impact on MS course is not well understood. We tried to investigate the possible role of adolescent diet in late-onset multiple sclerosis (LOMS) odds. LOMS patients were obtained from the National MS Registry of Iran. Controls were sex and age matched with no history of neurological disorders. We assessed dietary factors using a questionnaire based on multinational studies. Food consumption levels were classified into low, medium, and high for each item. Logistic regression models were used to evaluate diet's impact on LOMS odds. We included 83 LOMS cases and 207 matched healthy controls. The mean age for LOMS patients was 61.14, compared to 61.51 years for controls. The results showed that higher consumption of dairy as in the third tertile associated with 79% decline in LOMS odds (AOR: 0.21; 95%CI: 0.09-0.47). Higher seafood consumption, in the third tertile was associated with a decrease in the odds of LOMS (AOR: 0.32; 95%CI: 0.14-0.72). Furthermore, increased nut consumption, in the third tertile (AOR: 0.37; 95%CI: 0.18-0.77), decreased the odds of LOMS. Additionally, higher consumption of fruits (AOR: 0.22; 95%CI: 0.07-0.63) and vegetables (AOR: 0.26; 95%CI: 0.12-0.55) was linked to a reduced odds of LOMS. This research highlights the advantageous impact of dairy products, seafood, nuts, fruits, and vegetables in lowering the LOMS odds. Hence, advocating for nutrition role in development of LOMS could represent a preventive measure for people susceptible to MS.

Immune activation is energetically costly, yet the extent to which physiological costs translate into consequences for organismal performance remains unclear. Because immune responses and energy allocation can vary with age, we experimentally manipulated the type and intensity of immune stimulation (injection versus implantation) in young and old female Tenebrio molitor and quantified the effects on metabolic rate and survival under food limitation. Immune stimulation elevated metabolic rate, with treatment explaining approximately 30% of the variance in log-transformed metabolic responses, particularly following injection-based challenges. In contrast, survival under food limitation was only weakly affected by immune treatment (∼2% variance explained), but was strongly influenced by body mass (∼15%). Metabolic responses differed between young and old females, indicating age-dependent physiological sensitivity to immune challenge, whereas the effects of immune treatment on survival were similar across age classes. These findings demonstrate that immune activation produces pronounced physiological costs, but these costs do not necessarily translate into reduced starvation tolerance. Age modifies physiological responses to immune challenge, yet energetic reserves remain the primary determinant of survival under food limitation.

Physical activity reduces the risk of mortality and age-related chronic diseases, yet its association with biological age measured by DNA methylation (DNAm) clocks remains unclear. This systematic review and meta-analysis aims to evaluate the association between physical activity and biological age measured by DNAm clocks. In this systematic review and meta-analysis, we conducted a systematic search of Embase, Cochrane Central Register of Controlled Trials, PubMed, Ovid, Scopus, and Web of Science from Jan 1, 2011, to June 6, 2025, to identify articles on the associations of physical activity and DNAm age, epigenetic age acceleration (EAA), or epigenetic age deviation in humans. Studies were included if they were peer-reviewed, published in English, included a study population with a mean or median age of 18 years or older, and investigated the association between DNAm clocks and physical activity in humans. Studies were excluded if the study population was a disease-specific population without controls. We evaluated risk of bias using an adapted Newcastle-Ottawa Scale and Cochrane Risk of Bias scale. We then performed a random-effects meta-analysis using reported or estimated standardised β coefficients and SEs. We also conducted a publication bias analysis and influence analysis. The study was registered with PROSPERO, CRD42024499021. We identified 34 437 articles and, after removal of duplicates and screening, 44 studies were included in the systematic review comprising 145 465 participants: 62 887 (43·2%) females and 82 578 (56·8%) males, with mean ages ranging from 24·1 years to 78·5 years. Across studies, higher levels of physical activity were generally associated with lower DNAm age, although many individual associations did not reach statistical significance. Seven cross-sectional studies contributed to the meta-analysis. Each one SD higher in metabolic equivalent of tasks-min per week was associated with 0·03 SD lower Horvath EAA (β=-0·03 [95% CI -0·05 to -0·01]) and 0·09 SD lower GrimAge EAA (-0·09 [-0·12 to -0·05]). No statistically significant association was observed for Hannum EAA or PhenoAge EAA. Higher physical activity is significantly associated with lower biological age as measured by Horvath EAA and GrimAge EAA. However, evidence is predominantly from cross-sectional studies, limiting causal inference. Future longitudinal studies and clinical trials using standardised, objectively measured physical activity are warranted to clarify dose-response relationships, and to determine whether physical activity can causally modify ageing trajectories, thereby informing precision strategies for healthy longevity. The National University of Singapore and the National Medical Research Council of Singapore.

Severe acute malnutrition (SAM) affects millions of children globally, and treatment coverage remains below 30% in many settings, including Ethiopia. Although the Community-Based Management of Acute Malnutrition (CMAM) program has expanded nationwide, persistent service gaps remains, partly due to insufficient evidence for accurate cost estimation and budgeting. To address this gap, this study estimated the total economic cost, including provider-side financial and caregiver costs, of treating SAM through the CMAM program in two operational areas of Action Against Hunger, Ethiopia, and identified major cost drivers. A cross-sectional cost analysis was conducted in Girawa district (Oromia Region) and Adadle district (Somali Region) in 2024 from a societal perspective, including both provider-side financial and caregiver costs. Provider-side financial costs include personnel, medical supplies, therapeutic foods, equipment, transport and storage, and training and supervision. Caregiver costs include both direct costs (transport, food, and hospitalization-related expenses) and indirect costs (lost income and coping strategies). Provider-side financial costs were extracted and estimated using the FANTA CMAM costing tool. The tool automatically generated total cost per district, and the provider-side financial cost per SAM child was calculated by dividing total annual provider-side financial expenditure by the number of SAM cases treated. Caregiver costs were collected through structured exit interviews, analyzed using Excel, and summarized as mean cost per treatment episode. The mean caregiver cost was added to the provider-side financial cost to estimate the total economic cost per SAM child. The total annual provider-side financial cost for SAM treatment was USD 386,598 in Girawa district and USD 289,433 in Adadle district. Supplies, particularly RUTF and therapeutic milk, constituted the largest cost category in Girawa (57.7%), whereas repeated SAM-specific training and supervision represented the major share in Adadle (40.9%). The average provider-side financial cost per SAM child was USD 171.1 in Girawa and USD 325.2 in Adadle. The average caregivers incurred cost per SAM episode was USD 53.55. The total economic cost per SAM child, including caregiver expenses, was USD 224.65 in Girawa and USD 378.75 in Adadle. There is substantial variation in the cost of delivering SAM treatment across districts, highlighting the importance of context-specific district-level cost analyses. SAM-specific supplies and training intensity were the primary cost drivers. The incorporation of the household economic burden highlights an important but often overlooked dimension of treatment costs. These findings provide realistic district-level unit costs that can directly guide partners and governments in estimating resource needs for annual response plans while strengthening CMAM budgeting, planning, scaling up in Ethiopia.

Most coastal urban environments are characterised by a large concentration of shipping ports, walkways, and other built infrastructures. These are commonly associated with high levels of artificial light at night (ALAN), a pervasive anthropogenic driver that erodes natural light cycles and impacts the ecology of benthic communities. However, it is not well known whether the spatial configuration of coastal built structures may influence the effects of light pollution on community structure. Here, we conducted field surveys in natural rocky habitats and on breakwaters directly lit by streetlights (ALAN), and in matched unlit zones (without-ALAN), along the coast of northern and central Chile (20°S-32°S), to examine the influence of light pollution on the diel activity and density of the intertidal grazer guild and on the biomass of their main food resource, biofilm, in both habitat types. The patchy distribution of artificial light on the breakwaters seems to allow the co-occurrence of diurnal and nocturnal grazers at night, resulting in no major alteration of grazer densities with light pollution. The density and night-time activity of diurnal grazer species increased in parallel with an increase in the biofilm biomass under lit conditions in the topographically more homogeneous natural rocky habitat. On the lit breakwaters, biofilm also increased but no change in grazer densities was found, most likely related to the presence of dark zones. Our results indicate that the influence of coastal streetlight pollution on benthic grazers can be dampened by the presence of among-boulder interstices in the built structure. Increases in biofilm, the main food of grazers, by artificial light, may reinforce grazing pressure in both rocky habitats. Promoting a balanced mix of built habitats and conserving urban natural rocky shores while reducing coastal light pollution from streetlights could help prevent impacts on different functional groups due to accelerated urban infrastructure expansion.

Home environments shape children's dietary habits, but which factors are most influential is unclear. The study purpose was to identify factors in the home environment associated with child intake of fruit and vegetables (FV) and sugar-sweetened beverages (SSBs) using a national dataset collected in 2013-2015 in the U.S. Data from 5,138 school-aged children (4-15 years old) from 130 U.S. communities were collected in 2013-2015. Parents and/or children completed a dietary screener and additional survey questions to assess household socioeconomic status (SES), grocery shopping sources, home food availability, social support for healthy eating, eating out frequency, and other home eating and related behaviors. Other child characteristics included breastfeeding history, intake of school foods, and participation in other nutrition programs. Community variables included predominant race/ethnicity and SES. Classification and regression trees (CART) identified key predictors of intake. The FV and SSB CARTS had 14 and 12 terminal groups, respectively. Children with the highest FV intake (0.54 SD from mean cups/day; 13% of sample) had fruit more often available at home, dark green vegetables more often available at home, ate dinner with family more often, had SSBs less often available at home, and were breastfed longer. Conversely, children in the two groups with the lowest FV intake either had fruit less often available at home, and family never complimented their eating (-0.86; 2%), or they had family that rarely or sometimes complimented their eating, and perceived school lunches as unhealthy (-0.87; 1%). For SSB intake, the lowest consumers (-0.63 SD from mean tsp/day sugar; 17%) never or rarely had SSBs available at home, and lived in higher SES communities. Children in the two groups with the highest SSB intakes had SSBs available at home more often, and lived in a SNAP-participating household and either ate out less often, used a phone/computer for social networking, and had SSBs available at home very often (1.3; 1%), or they ate out more often, and were breastfed for a shorter duration (1.1; 5%). Home availability of FV and SSBs were the most salient predictors of intake of both FV and SSBs, while other predictors differed between FV and SSB intake. Study findings highlight several actionable home-environment strategies to test in future studies to improve school-aged children's diets.

Filamentous fungi have played an undeniable role in the biosphere for hundreds of millions of years and, for humans, have increasingly been developed as sources of food, medicine and other resources; their uses growing to include materials science and bioremediation. As these developments have gained pace, a variety of disparate fields are making new advances and turning to synthetic biology to increase their potential. As genetic sequencing and computing technologies widen our knowledge of the different species of fungi, synthetic biology enables us to harness and expand their unique traits. These developments are discussed in the context of these existing and emerging applications of engineering and synthetic biology, so that they might be more widely understood, thus promoting the standardisation of language and innovation. Certain challenges and research gaps within the investigated research fields are also highlighted, as are various opportunities and connections found during the exploration of these fields, and the impact of developing technologies including 3D printing and cell-free systems.

Hidradenitis suppurativa (HS), an inflammatory skin disorder characterized by painful nodules and abscesses, has varying prevalence among different races/ethnicities. This study explored the social drivers of health, burden, and impact of HS among different racial and ethnic groups. An online, cross-sectional survey was conducted among adult patients with HS (September 2023-December 2023) in the USA. Patients were recruited through HS Connect (patient advocacy group) and AmeriSpeak (US national sample panel). Descriptive data were collected using patient-reported outcome measures and de novo questions about patients' disease knowledge and perception, healthcare access and utilization, impact on quality of life (QoL), and social impact. All analyses were descriptive and stratified by racial/ethnic groups. The study included 583 patients (mean age, 34.8&#xa0;years; 95.5% female) representing a range of racial backgrounds: Black or African American (n&#x2009;=&#x2009;273; 46.8%), white (n&#x2009;=&#x2009;236; 40.5%), Two or More Races (n&#x2009;=&#x2009;47; 8.1%), American Indian or Alaska Native (n&#x2009;=&#x2009;18; 3.1%), Asian (n&#x2009;=&#x2009;7; 1.2%), and Native Hawaiian and Other Pacific Islander (n&#x2009;=&#x2009;2; 0.3%). Ethnic representation also varied (Hispanic/Latino&#x2009;=&#x2009;n&#x2009;=&#x2009;76; 13.0%). Patients of all races and ethnicities reported considerable QoL impact (Dermatology Life Quality Index, EQ-5D-5L), with results for smaller subgroups (n&#x2009;<&#x2009;10) included for descriptive completeness only and not intended for comparison with other groups. During flaring, most patients used over-the-counter products/medications (54.2%) or nonmedical intervention/home remedy (56.9%) Up to 36.5% of patients reported challenges in procuring food, utilities, medicine/healthcare, phone, clothing, or childcare when needed in the past year. Among those who paid out-of-pocket for their HS treatment, 55.6% reported that it stopped them from visiting a healthcare provider for treatment. The findings indicate a high burden and impact of HS across all races and ethnicities. Patients reported social drivers of health and challenges with healthcare utilization, indicating the need for integrating social workers and care management teams in dermatology practice, which could facilitate improved care of patients with HS. Hidradenitis suppurativa is a painful skin condition that causes lumps and abscesses. It affects people of all races and ethnicities but is more common in Black or African American individuals. This study surveyed 583 adults in the USA to understand how hidradenitis suppurativa affects people from different racial and ethnic backgrounds. Our focus was on how the disease impacts their daily lives, their ability to access healthcare, how often they visit doctors, their quality of life, and their mental and emotional well-being. Most people said that hidradenitis suppurativa lowers their quality of life and makes daily activities harder. During flaring, many used home remedies instead of seeing a doctor. People suffering from hidradenitis suppurativa also reported trouble getting basic needs such as food, medicine, and transportation. These challenges occurred among patients from different racial and ethnic groups; results for very small subgroups (Asian, Native Hawaiian/Other Pacific Islander) are reported descriptively only and should not be interpreted as representative of these groups or compared with other groups. The research underscores the importance of improving awareness and tailoring care for people with hidradenitis suppurativa, particularly those facing barriers to healthcare.

The effect of sodium chloride concentration (0-0.20&#x202f;M) on the structure and properties of wheat starch-acetylated starch (WS-AS) binary gel was investigated. The addition of an appropriate salt concentration decreased the hardness, cohesion, and chewiness of the WS-AS binary gel (0.02-0.05&#x202f;M). In addition, the amylose leaching content and spin-spin relaxation time (T2) of the saline sample were lower than those of the salt-free sample. Correlation analysis indicated that changes in gel properties were consistent with the inhibition of system retrogradation at an appropriate salt level (0.02-0.05&#x202f;M). Overall, an appropriate salt concentration suppressed retrogradation in the WS-AS system by modulating hydrophobic interactions and restricting chain entanglement, thereby retarding starch-chain rearrangement and providing guidance for the design of wheat starch-based food matrices with tailored properties.

Fenofibrate, an active pharmaceutical ingredient (API) of the fibrate class approved by the U.S. Food and Drug Administration (FDA) for the treatment of hypercholesterolemia and hyperlipidemia, has emerged as a promising candidate for repurposing in cancer. Indeed, beyond its lipid-lowering effects, fenofibrate has demonstrated antitumor properties, including antiproliferative and cytotoxic effects in normoxia (21% O2) in preclinical models of GBM. In addition, fenofibrate may inhibit hypoxia-inducible factor-1 alpha (HIF-1&#x3b1;) and reduce the expression of hypoxia-inducible genes, potentially overcoming hypoxia-induced chemoresistance. These findings, combined with its established clinical safety profile, support further investigation of fenofibrate as a potential therapeutic strategy in GBM. On this basis, physico-chemical characterization of fenofibrate was assessed to determine its ability to cross the blood-brain barrier. We determined in vitro on GBM cell lines U251-MG, U87-MG and GL261, the efficacy of fenofibrate in decreasing GBM cell viability and proliferation under normoxia (21% O2) and hypoxia (1% and 0.2% O2). We investigated the kinetics of its internalization by HPLC. In addition, the safety of fenofibrate was evaluated on non-tumoral brain cells. Dunn's post-hoc test was used after a significant Kruskal-Wallis. Being practically insoluble in water, fenofibrate was dissolved in dimethyl sulfoxide (DMSO) for studies. Primary astrocytes showed no signs of toxicity following treatment with fenofibrate. The effect of fenofibrate on GBM cell lines was studied at various time points and exhibited a cell type-, time- and concentration-dependent cytotoxicity with an LC50 of 25, 43.7 and 49.6&#xa0;&#xb5;M for U251-MG, U87-MG and GL261 cells, respectively. Interestingly, fenofibrate uptake was confirmed, 12.9&#x2009;&#xb1;&#x2009;5.7% and 14.2&#x2009;&#xb1;&#x2009;6.6% of fenofibrate was found in U251-MG and U87-MG cells, respectively. Intracellular concentrations of fenofibrate increased over time and no precipitation was observed. In hypoxia (1% and 0.2% of O2), the cytotoxic effect of fenofibrate was still present, albeit decreased. Furthermore, fenofibrate induced a cytostatic effect on U251-MG and U87-MG under both normoxia (21% O2) and hypoxia (1% and 0.2% O2), reducing their proliferation. Under the experimental conditions tested, namely in vitro studies, fenofibrate appeared more efficient compared with temozolomide, the standard treatment for GBM. This study demonstrated the cytotoxic and cytostatic effect of fenofibrate on GBM cells. These results indicate that fenofibrate may be a therapeutic alternative for GBM treatment.

Early and accurate detection of plant leaf diseases is an essential requirement for precision agriculture, given their severe impact on global food security. While much has been done recently, many deep learning-based approaches will still fail in real-world tests because of challenges such as background clutter, differences in illumination, occlusion, or the fact that visual&#x2002;symptoms for these diseases can be very subtle early on. Traditional CNN- and Transformer-based architectures generally lack accurate lesion localisation and interpretability, hindering their practical deployment in agricultural decision-support tools. To address these issues, we present LDDHybridNet, a region-based, explanation-friendly deep learning framework that can identify leaf disease at an early, accurate stage. It then applies preprocessing steps guided by ROI, based on leaf segmentation from the U-Net, followed by a compact CNN-based spatial feature-extraction framework. We arrange spatial feature embeddings extracted from lesion regions into an ordered sequence and employ a Bi-LSTM with attention to model structured contextual dependencies, allowing progression-aware feature learning without requiring actual temporal image sequences. Lastly, Grad-CAM-based post-hoc explainability is employed to interpret model decisions, enabling transparent visualisation of disease-relevant regions. We conduct extensive experiments on the PlantVillage benchmark and the FieldPlant dataset and show that LDDHybridNet consistently outperforms representative CNN, transformer, and hybrid baselines across multiple evaluation metrics. Although the near-ceiling performance on PlantVillage reveals the dataset's artificial nature, the proposed framework achieves 95.37% accuracy under real-world field conditions and 92.84% on weak-lesion early-stage samples, demonstrating the method's robustness and early-stage detection potential. The performance boosts are statistically significant (P&#x2009;<&#x2009;0.01). In general, LDDHybridNet is an interpretable and robust deep learning framework for leaf disease detection, which can support data-driven crop protection and precision agriculture&#x2002;applications.

The functional properties and application performance of poly-&#x3b3;-glutamic acid (&#x3b3;-PGA) are strongly dependent on its molecular weight (MW). However, the precise control of MW remains challenging, significantly hindering its high-value applications in the food, agricultural, cosmetic, and pharmaceutical sectors. Heterologous enzyme expression has emerged as a powerful and specific strategy for regulating the MW of &#x3b3;-PGA. In this study, &#x3b3;-DL-glutamyl hydrolase (BvPgdS45) from Bacillus velezensis CAU263 was heterologously expressed in Komagataella phaffii, achieving an activity of 102.7 IU/mL following high-cell-density fermentation. BvPgdS45 exhibited optimal activity at a pH of 7.0 and temperature of 50 &#x2103;. Subsequently, its effects on &#x3b3;-PGA degradation property were evaluated. The weight-average molecular weight (Mw) of &#x3b3;-PGA decreased from 3.3&#xd7;106Da to 1.1&#xd7;105Da after 3h of enzymatic hydrolysis at enzyme dosages ranging from 0 IU/mL to 10 IU/mL. Furthermore, &#x3b3;-PGA with different MW was produced using B. velezensis CAU263 via in situ enzymatic hydrolysis. Products with Mw ranging from 5.1&#xd7;105 Da to 2.1&#xd7;106 Da were generated, while the &#x3b3;-PGA yield increased from 62.6g/L to 73.7g/L in a 5L fermenter. Overall, this study demonstrates the effectiveness of BvPgdS45 expressed in K. phaffii for degrading &#x3b3;-PGA and provides an efficient in situ hydrolysis strategy for the precise regulation of its MW.

Microfibers (MFs) are a prevalent form of microplastics in aquatic environments and are frequently ingested by aquatic organisms. In nature, individual fibers do not always remain straight but can bend, coil, or become partially self-entangled, potentially altering their biological interactions. However, how such morphological variability influences MF ingestion by benthic gastropods remains poorly understood. Here, we exposed the freshwater snail Sinotaia quadrata to 50 items/L, within the range reported for freshwater systems, of polyethylene terephthalate and polyamide MFs, including elongated single fibers and coiled forms derived from the same individual fibers of corresponding lengths but exhibiting smaller external dimensions. Regardless of food availability and across all tested size classes, snails ingested significantly more elongated single fibers than coiled MFs. Ingestion of both forms peaked within 6 h; however, elongated fibers exhibited longer retention times in the digestive tract, whereas coiled forms were largely egested within 24 h. Microscopic observations indicated that radula-mediated feeding interactions more effectively captured elongated, flexible fibers, whereas coiled MFs were more likely to undergo transient contact without sustained retention and be dislodged during repeated radula-mediated movements. Scanning electron microscopy and micro-Raman analyses further revealed localized surface irregularities on ingested fibers. Together, these results provide experimental evidence that feeding interactions may enhance the bioavailability of elongated MFs and may facilitate their physical alteration. Our findings underscore the importance of fiber morphology and feeding mode in shaping MF exposure pathways and fate in benthic freshwater ecosystems.

Mitochondria represent central regulators of neuronal function, and their network is dynamically restructured via fission and fusion. The mitochondrial fission factor (MFF) serves as an adaptor protein that recruits and organizes the core fission machinery at the outer mitochondrial membrane. Here, we investigated the role of MFF in Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) in their regulation of systemic energy homeostasis. We demonstrated that mice lacking MFF in AgRP neurons exhibited increased mitochondrial size, both in AgRP neuron somata and their axonal compartments. This translated into increased mitochondrial Ca2+ uptake capacity, increased mitochondrial membrane potential, and a shift toward a more reduced mitochondrial NAD(P)H redox state. Ultimately, these changes resulted in increased neuronal excitability and neurotransmitter release to functionally enhance dynamic food intake during energy state transitions. Collectively, MFF-dependent mitochondrial fission links cell-type-specific neuronal mitochondrial dynamics via mitochondrial Ca2+ handling to control systemic metabolism.

To evaluate finerenone-associated adverse events (AEs) and to investigate the association between finerenone use and renal injury via data mining of the Food and Drug Administration Adverse Event Reporting System (FAERS). To minimize statistical bias, the data extraction period was set from database inception (2004) to provide a stable background for disproportionality analysis. Four disproportionality algorithms (ROR, PRR, BCPNN, and MGPS) and stricter case-screening methods were employed to improve analytical precision. Additionally, a clinical priority evaluation was conducted to rank clinical risks and surveillance levels for these AEs. Supplementary analysis was performed to assess the relationship between finerenone and renal injury, as well as associated risk factors. A total of 1316 finerenone-related reports were identified. 30 AEs were detected as significantly positive signals, with most being related to renal function (15 PTs, 50%), blood pressure (5 PTs, 16.67%), and blood potassium (4 PTs, 13.33%). Among them, blood glucose increased, blood creatine increased, and flank pain were new potential AEs. Acute kidney injury, hyperkalemia, renal impairment, glomerular filtration rate decreased, blood creatinineincreased, blood potassium increased, and hyponatremia exhibited moderate clinical priority levels and warrant further study. Signals reflecting renal injury were detected in patients regardless of baseline nephropathy. Male sex, taking more than 3 drugs, and using amlodipine may be risk factors for finerenone-related nephrotoxicity. These results highlight new finerenone-related AEs, provide ranked guidance for pharmacovigilance through clinical priority evaluation, and clarify factors that influence renal injury, providing guidance for individualized treatment and improved drug safety.

Reptiles often inhabit environments that are in close proximity to humans and livestock, creating opportunities for parasite transmission. They are common in areas where they find shelter, food and warmth. The Bengal monitor lizard (Varanus bengalensis), a member of the family Varanidae, represents one of the largest groups of extant poikilothermic predators. Monitor lizards are known to harbor several tick species that serve as vectors for a variety of pathogens. No prior information is available in the literature regarding ticks infesting V. bengalensis in Pakistan as well as regarding the occurrence of Toxoplasma gondii in these ticks. Therefore, we aimed to determine the molecular prevalence of T. gondii in Amblyomma gervaisi ticks (n&#x2009;=&#x2009;93) collected from 24 V. bengalensis in Buner District, Khyber Pakhtunkhwa Province, Pakistan, between May and September 2023. Polymerase chain reaction (PCR) amplified a 300&#xa0;bp fragment specific for the ITS-1 region of T. gondii in 10 of the 93 (11%) A. gervaisi ticks. DNA sequencing and BLAST analysis confirmed the presence of T. gondii. Phylogenetic analysis showed that these sequences clustered with the ITS-1 sequences of T. gondii detected in reptiles and mammals from Pakistan, Brazil, China, Tunisia and Portugal. The prevalence of T. gondii in A. gervaisi was not limited to a specific tick sex, feeding stage or month of sampling. However, among the tick developmental stages, nymphs had the highest rate of T. gondii infection. In conclusion, for the very first time from Pakistan, we are reporting the presence of T. gondii in A. gervaisi that were infesting monitor lizards. We recommend that similar and large scale studies should be conducted in all those areas of Pakistan that are unexplored for the presence of T. gondii in A. gervaisi ticks. Prevalence of this parasite should also be screened in all the animals harboring these as well as other tick species. This will help in better understanding of T. gondii transmission to new hosts that will lead toward its effective control.