Mitochondrial diseases are clinically and genetically heterogeneous, often complicating diagnosis. Here, we describe four unrelated individuals with suspected mitochondrial disease who shared similar neuroimaging features, including bilateral symmetrical supra- and infratentorial white-matter abnormalities, together with variable movement disorders and intellectual impairment. Whole-genome sequencing identified the same homozygous MRPS22 variant (c.798_799delinsTA) in all four patients. MRPS22 encodes a component of the mitochondrial small ribosomal subunit (mtSSU). Functional studies in patient-derived fibroblasts showed impaired mitoribosome assembly and reduced de novo mitochondrial translation. Despite largely preserved steady-state levels of OXPHOS proteins, respiratory chain analysis identified a mild, isolated complex I deficiency. Proteomic profiling revealed reduced levels of mitochondrial ribosomal proteins and dysregulation of mitochondrial translation pathways. In line with the proteomic findings, RNA sequencing of fibroblasts from three patients revealed a distinct transcriptional signature compared with controls, with mitochondrial translation emerging as the most affected pathway. Mitochondrial-encoded transcripts were decreased, whereas nuclear-encoded mitochondrial genes were generally increased. Structural modelling suggested that the variant disrupts key interactions important for mitoribosome stability. While previously reported MRPS22 variants have been associated with severe, often prenatal-onset disease, the individuals described here exhibited a milder phenotype, thereby expanding the clinical spectrum of MRPS22-related disorders. Together, these findings support the pathogenicity of this variant and highlight the value of integrated genomic and functional analyses in diagnosing mitochondrial disease.

Non-van-der-Waals (non-vdW) layered magnets provide bonding degrees of freedom beyond dispersion-dominated stacks, yet how dilute interlayer covalent bridges influence bulk-to-monolayer evolution remains insufficiently understood. Using first-principles calculations, we investigate FePd2Te2 (FPT), a layered ferromagnet with sparse interlayer Pd─Te bridges. These bridges exhibit a covalent component, while the cleavage energy remains in the vdW-like range (∼0.51 J·m[-2]), establishing FPT as an exfoliable non-vdW layered magnet. Upon thinning from bulk to monolayer, local Fe moments and intralayer exchange terms increase slightly, whereas the Curie temperature decreases from 173 to 27 K. Analysis of multiplicity-weighted exchange contributions indicates that this suppression of TC is governed primarily by the weakening and eventual disappearance of interlayer ferromagnetic exchange J3, with enhanced antiferromagnetic competition from J2 providing an additional destabilizing contribution. Meanwhile, orbital reorganization near the Fermi level sustains a relatively large easy-plane magnetocrystalline anisotropy (∼1.86 meV per Fe in bulk) with a moderate enhancement (∼8.6%) in the monolayer, gives rise to a dimensionality-dependent reversal of magnetoelastic response under biaxial strain, and leaves the near-EF spin polarization comparatively robust up to ±5% strain. These results identify FPT as a representative exfoliable non-vdW magnet and clarify how sparse interlayer covalent bridges govern its thickness-dependent magnetic evolution.

We report a highly portable dual modality aptasensing platform for the detection of surface glycoprotein, hemagglutinin (HA), of the influenza A virus. The sensing device consists of a colorimetric detection component composed of a microfluidic paper-based analytical device (μPAD) having four analyte testing areas, as well as a flexible, miniaturized three-electrode system. Both sensing components are brought together and encapsulated within a microfluidic holder, which increases the integrity of the device, mediates sample flow, and allows for ease of translation to point-of-care (POC) use. Colorimetric detection using the μPADs resulted in a detection limit of 0.62 μg/mL in buffer over a linear range of 0.75-50 μg/mL HA (R[2] = 0.9905), with stability over 30 days (up to 97.3% signal retention). The electrochemical component uses impedance spectroscopy to measure changes in charge transfer resistance (Rct) upon aptamer-target recognition using hexaamineruthenium(III) chloride as a redox probe. Through the addition of the electrochemical component, the detection limit was improved to 8.5 ng/mL in buffer over a linear range of 0.015-25 μg/mL HA (R[2] = 0.9730), with stability over 7 days (113.1% signal retention). When using the device with a modeled real sample medium of artificial human saliva, colorimetric analysis resulted in detection of HA down to 1.0 μg/mL, while the electrochemical component resulted in a detection limit of 14.9 ng/mL. Additionally, while carrying out tests in dilute human saliva composed of a fifty-fifty mixture of pooled human saliva and TE buffer, detection limits using the μPAD nearly matched the artificial saliva's calculated limit at 1.04 μg/mL and the electrochemical platform reached a comparable but even lower limit of detection at 4.11 ng/mL HA, displaying promise for real world applicability. Both sensing platforms exhibited excellent selectivity when used against other surface proteins of common viral pathogens. While using the combined device, there are five target-testing zones (4 colorimetric, 1 electrochemical), decreasing the likelihood of false-negative/false-positive outcomes.

Non-anastomotic stricture (NAS), a severe liver transplantation (LT) complication, is pathologically defined by biliary fibrosis, with unclear mechanisms and limited pharmacological therapeutic strategies. Single-cell RNA sequencing was performed on the bile duct tissues of NAS patients, ongoing (fibrosis persistent group) or succeeding (fibrosis remission group) in endoscopic treatment. Integrated analysis indicated that biliary epithelial-mesenchymal transition (EMT) and fibrosis were reduced in the fibrosis remission group than in the fibrosis persistent group. VIM[+] biliary epithelial cell (BEC), a novel EMT-related BEC subcluster, exhibited robust activation of the EMT pathway and decreased during biliary fibrosis remission. Mechanistically, extracellular hypoxia and TGF-β signaling enhanced CREM transcriptional activity in VIM[+] BEC, which promotes EMT by regulating the VIM expression. CREM knockdown in BEC significantly suppressed hypoxia- and TGF-β-induced VIM expression. BEC-specific Crem knockout (Crem[fl/fl]; Sox9-Cre[+/-]) suppressed Vim expression, EMT, and fibrosis in rats post-LT. Melatonin administration reduced Crem expression, biliary EMT, and fibrosis in rats post-LT. An explorative clinical trial preliminarily confirmed that some NAS patients showed improved liver function after melatonin treatment. Our findings revealed that the hypoxia/TGF-β-CREM-VIM axis modulates the VIM[+] BEC subcluster, which in turn drives biliary EMT and fibrosis, and melatonin emerges as a promising drug candidate for NAS-related biliary fibrosis.

Diarrhea caused by amoxicillin (A) or amoxicillin-clavulanate (AC) is common in children, and the induced dysbiosis is often characterized by a severe reduction in bifidobacteria. However, bifidobacteria are extremely antibiotic-sensitive, and their co-administration with antibiotics is likely unwise. The B. breve PRL2020 strain is an A- and AC-resistant probiotic. In a multicenter, randomized, controlled, non-profit study, we tested the tolerability and efficacy of the PRL2020 strain when co-administered to children (3-12 years; N = 121) undergoing A or AC therapy, attempting to interpret the results obtained by observing the intestinal microbiota in a subgroup (N = 41) of enrolled children. In children treated with the probiotic, the therapy was well tolerated and the incidence of diarrhea was significantly reduced by approximately 70% (p < 0.01). Considering only children with diarrhea, in the probiotic-treated group the onset was postponed by about 15 h, and the symptom lasted 19 h less. Gut microbiota richness was significantly reduced in both groups, without significant differences between probiotic-treated and control children. At the phylum level, antibiotic treatment was associated with an increase in Proteobacteria and a reduction in Actinobacteria, with larger apparent shifts in the control group. Bifidobacteria, particularly B. breve, decreased in controls and increased in treated subjects (p < 0.05), despite not being among the most abundant taxa contributing to the majority of the microbial community. Finally, although only in a trend-based manner, butyrate-producing bacteria decreased less in probiotic-treated children, whereas an increase in succinate-consuming bacteria was observed in controls. Co-administering the B. breve PRL2020 strain with A or AC in children significantly reduces diarrheal symptoms and antibiotic-related dysbiotic status. New blinded, placebo-controlled studies with a more robust sample size for microbiota analysis will have to confirm our data.

Tree rings are used for biomonitoring environmental conditions, providing insight into chemical constituents present during a tree's growth. Here, we report the utilization of tree rings and aerial parts (i.e., leaves, shoots, and fruits) of Muntingia calabura Linn. (locally known as mansanitas or aratiles), as well as soil near the trees, to monitor spatial distribution of the presence of mercury (Hg) in 18 cities and municipalities of Cebu, Philippines. While uncommon, tropical tree rings from core samples also provide insight into the chronology of mercury uptake in M. calabura trees between 2003 and 2016. Samples from a total of 65 sites are collected and analyzed for Hg using a Milestone Direct Mercury Analyzer DMA-80 following US EPA Method 7473 and validated using standard reference materials, i.e., NIST SRM 1515 (apple leaves), NIST SRM 1575a (pine needles), and NIST SRM 2687 (soil). Soil parameters are analyzed using standard US EPA methodologies. Mercury concentrations are found to range from 1.52-20.4 parts per billion (ppb, tree cores), 8.75-105 ppb (leaves), 3.82-166 ppb (shoots), 1.40-8.45 ppb (fruits), and 6.29-247 ppb (soil). Spatial and temporal distribution maps of Hg concentrations in M. calabura generated from the collected data, while not conclusive in terms of source attribution, indicate aerial transport and clearly show significant increases in Hg concentrations near heavily industrialized areas or landfills, as well as a general increase in Hg levels from south to north. Analysis of the Hg concentrations in tree cores shows a decreasing trend from 2003 to 2016, suggesting that Hg levels in the environment have been steadily declining, although lateral translocation of the metal from bark to pith remains a factor that cannot be dismissed. This study demonstrates the viability of utilizing aerial parts and tree rings of M. calabura to detect patterns of spatial and temporal distribution of mercury and potentially other metals. Local governments can take advantage of this knowledge to help formulate policies regarding the control of gaseous emissions and disposal of effluents and sludge from industrial facilities, power plants, and sanitary landfills.