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Exploring the link between osteosarcopenia and osteoarthritis in prediabetic adults using NHANES data

Address the psychological toll of kidney disease

Characterisation of an autochthonous mouse ccRCC model of immune checkpoint inhibitor therapy resistance

Abstract Many metastatic clear cell renal cell carcinomas (ccRCC) are resistant to immune checkpoint inhibitor therapies, however the mechanisms underlying sensitivity or resistance remain incompletely characterised. We demonstrate that ccRCCs in the Vhl/Trp53/Rb1 mutant mouse model are resistant to combined anti-PD-1/anti-CTLA-4 therapy alone and in combination with additional therapeutic agents that reflect current ccRCC clinical trials. However, in some animals in vivo checkpoint therapy allowed isolated splenic T cells to recognise cultured ccRCC cells from the same animal, implicating the tumour microenvironment in suppression of T cell activation. We identified putative immunosuppressive myeloid cell populations with features similar to myeloid cells in the microenvironment of human ccRCC. The expression patterns of immune checkpoint ligands in both the mouse model and in human ccRCC suggests that several checkpoint systems other than PD-1 and CTLA-4 are likely to represent the dominant T cell suppressive forces in ccRCC. Our findings characterise an autochthonous mouse ccRCC model of immune checkpoint inhibitor therapy resistance and pave the way for a systematic functional dissection of the identified potential molecular barriers to effective immune therapy of ccRCC.

UPLC-HRMS-MS profiling of Ludwigia adscendens subsp. diffusa aerial parts and investigation of the anti-inflammatory effect

Abstract Ludwigia adscendens subsp. diffusa (Forssk.) P.H. Raven, also known as L. stolonifera, is an aquatic herb belonging to family Onagraceae and widely distributed in canals and drains in the Nile Delta, Egypt. The main goal of the current study is to investigate the metabolic profile of L. adscendens aerial parts using ultra-high performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS/MS) and investigation of its anti-inflammatory activity. A total of 168 metabolites were identified by UPLC-MS/MS analysis in negative and positive modes belonging to several phytochemical classes including phenolics (57), flavonoids (26), terpenoids (25), sterols (23), fatty acids (11), coumarins (7) organic acids (5), sugar derivatives (5), lactones (4), acids (3), and glycoside (2). The UPLC-MS analysis of L. adscendens revealed identification of a diverse array of phytochemicals which contribute to its potential pharmacological properties. The identification of bioactive metabolites in L. adscendens aerial parts including gallic acid, quercetin, ellagic acid, and betulinic acid can impart biological activities including antioxidant and anti-inflammatory activities. The anti-inflammatory activity was investigated for L. adscendens methanol and ethyl acetate extract using nitric acid inhibition assay revealing IC50 of 26.4 and 23.9 µg/ml, respectively, compared to resveratrol as a standard anti-inflammatory with IC50 value of 14.2 µg/ml. These findings can highlight the importance of L. adscendens aerial parts as a potential source of bioactive metabolites.

A PBPK modeling approach for personalized dose optimization of nicardipine in renal and hepatic dysfunction

Exclusive: Inside the thriving wild-animal markets that could start the next pandemic

SHAP-enhanced interpretive MGTWR-CNN-BILSTM-AM framework for predicting surface subsidence: a case study of Shanghai municipality

Effects of visual interface presentation location and auditory information on takeover performance in multimodal takeover interfaces for high-speed trains

Reusing of intraoperative exfoliated finger epidermis in the treatment of hand scar contracture in patients with RDEB

Speeding up ginseng growth to aid drug discovery

Integrative path modeling and QTL mapping identify maturity, stem strength, and cell wall composition driving lettuce resistance to Sclerotinia minor

Abstract Lettuce (Lactuca sativa) is highly vulnerable to Sclerotinia minor, the pathogen causing lettuce drop. Breeding for resistance is the most effective control strategy; however, full resistance has not been achieved, and current partial resistance sources are often linked with undesirable traits, such as early bolting. This study aimed to unravel the genetic basis of partial resistance to S. minor and its relationship with plant maturity (bolting), stem mechanical strength (SMS), and cell wall composition (CWC) using a recombinant inbred line (RIL) population derived from a cross between the susceptible iceberg cv. ‘Salinas’ and the resistant oil-seed accession PI 251246. Field evaluations indicated that resistance was linked to earlier bolting, stronger stems, and higher pentose content. Path analysis demonstrated that earlier-maturing plants exhibited increased resistance through enhanced SMS and modified CWC, particularly with higher xylose and lower arabinose levels. Further analysis indicated a significant relationship between syringyl lignin content and resistance, especially in plants with varying bolting responses. Three key quantitative trait loci (QTLs) on linkage groups (LG) 2, 6, and 7 were consistently associated with resistance, bolting, and SMS. Importantly, residual QTL analysis revealed that the resistance locus on LG7 acted independently of maturity, suggesting a distinct resistance mechanism. Callose synthase emerged as a key candidate gene within the LG7 resistance QTL, located near - but distinct from - genes associated with plant maturity and flowering. These findings provide valuable insights into decoupling resistance from early bolting, suggesting a pathway for breeding lettuce cultivars with improved disease resistance and delayed bolting.

Snowmelt and laying date impact the parental care strategy of a high-Arctic shorebird

Abstract Why parental care strategies can vary from uniparental to biparental care across taxa remains unclear, likely because various sets of ecological conditions are at-play. Here we tested ten possible hypotheses to decipher the direct and indirect impacts of critical factors likely to influence the parental care strategy during incubation in Sanderlings (Calidris alba), one of the few species that uses both types of care during that critical time of the breeding cycle. We examined three ecological factors (timing of local snowmelt, regional temperatures, and the North Atlantic Oscillation experienced just before breeding), one trophic factor (predation pressure), and two social factors (relative abundance of Sanderlings and their laying dates). Using long-term data from Greenland (2011–2023), path analyses revealed that laying date and snowmelt influence parental care strategies during incubation, with indirect climatic effects during migration and on breeding grounds. We observed a greater proportion of uniparental nests in years with delayed laying dates, and the reverse in years with delayed snowmelt. These findings underscore the complex interplay between environmental parameters and parental care strategies, offering insights into how these strategies are likely to respond to rapidly changing Arctic ecological conditions driven by climate change.

The polar regions hold crucial scientific secrets — and the time to study them is running out

Bioinformatics analysis of innovative multi-epitope vaccine utilizing MAGE-A, MAM-A, and Gal-3 for breast cancer management

Stereoretentive radical cross-coupling

Multimodal assessment of sleep-wake perception in insomnia disorder

Abstract Insomnia disorder is a prevalent health problem. The primary diagnostic criterion is a subjective complaint about reduced quantity or quality of sleep, which is often not observed in objective sleep measurements. Here we show that patients with insomnia disorder, characterized by substantial subjective sleep complaints, did not differ on objective measures of sleep continuity, sleep architecture, spectral power, spectral slope, and phase-amplitude coupling of slow oscillatory and spindle activity. Perception of wakefulness following serial awakenings from NREM sleep was frequent in both patients and controls, with no significant group difference. High frequency spectral power, as an index of cortical arousal prior to awakening, but not standard measures of sleep, predicted the perception of wakefulness across groups, possibly related to physiological wake-like activity during sleep. Our results support the notion that sleep-wake regulatory systems and direct sleep-wake perception are often intact in patients with insomnia disorder. These results propose empirical support for cognitive behavioral therapy for insomnia as the first-line treatment.

National preoperative HIV prevalence in China: a retrospective analysis of 4,753,874 surgical patients

Total cholesterol/high-density lipoprotein cholesterol ratio is a candidate predictor of survival outcomes in patients with metastatic renal cell carcinoma

How to keep astronauts healthy in deep space

Brain lateralization for perceiving direction of motion is reversed in Williams syndrome and related to BUD23

Abstract Lateralized nervous system function is phylogenetically old but fundamentally important for human brain function. Although altered in developmental and psychiatric disorders, we know little about its genetics. To understand the genetic origins of hemispheric specialization, we investigated laterality in a genetic disorder, Williams Syndrome (WS), caused by ~ 27 deleted genes on 7q11.2. Using a multidisciplinary approach combining individuals’ molecular genetic, electrophysiological, and behavioral data, we identify reversed lateralization, from right to left hemisphere for perceiving direction of motion in WS and show hemispheric strengths are inversely correlated. Moreover, we correlate decreased transcript levels of the deleted gene BUD23, with strength of the reversed lateralization and with decreased performance in mental rotation, another right hemisphere lateralized function. The results implicate dosed BUD23, an 18S ribosomal RNA methyltransferase, in human brain laterality, support an evolutionary origin and provide altered lateralization as a novel mechanism for impaired cognition in genetic and behavioral disorders.