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Purpose: Despite the publication of several randomized controlled trials (RCTs), it is not clear which technique for the treatment of focal chondral and osteochondral defects of the knee grants the best clinical outcome. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of microfractures (MF), autologous chondrocyte implantation (ACI), autologous matrix-induced chondrogenesis (AMIC), osteochondral autograft transplantation (OCT) at short (< 1 year), intermediate (1–5 years) and long-term (> 5 years). Methods: We carried out an NMA with Bayesian random-effect model, according to PRISMA guidelines. The search was performed in MEDLINE, EMBASE, Web of Science, CENTRAL, CINAHL, SPORTDiscus, clinicaltrials.gov, WHO ICTRP, from inception to November 2022. The eligibilities were randomized controlled trials on patients with knee chondral and osteochondral defects, undergoing microfractures, OCT, AMIC, ACI, without restrictions for prior or concomitant surgery on ligaments, menisci or limb alignment, prior surgery for fixation or ablation of osteochondritis dissecans fragments, and prior cartilage procedures as microfractures, drilling, abrasion, or debridement. Results: Nineteen RCTs were included. No difference among treatments was shown in the pooled comparison of patient reported outcome measures (PROMs) at any timepoint. Safety data were not available for all trials due to the heterogeneity of reporting, but chondrospheres seemed to have lower failure and reoperation rates. Conclusion: This NMA showed no difference for PROMs with any technique. The lower failure and reoperation rates with chondrospheres must be interpreted with caution since adverse event data was heterogenous among trials. The standardization of the efficacy and safety outcome measures for future trials on knee cartilage repair and regeneration is necessary.

Leishmania major is responsible for zoonotic cutaneous leishmaniasis. Therapy is mainly based on the use of antimony-based drugs; however, treatment failures and illness relapses were reported. Although studies were developed to understand mechanisms of drug resistance, the interactions of resistant parasites with their reservoir hosts and vectors remain poorly understood. Here we compared the development of two L. major MON-25 trivalent antimony-resistant lines, selected by a stepwise in vitro Sb(III)-drug pressure, to their wild-type parent line in the natural vector Phlebotomus papatasi. The intensity of infection, parasite location and morphological forms were compared by microscopy. Parasite growth curves and IC50 values have been determined before and after the passage in Ph. papatasi. qPCR was used to assess the amplification rates of some antimony-resistance gene markers. In the digestive tract of sand flies, Sb(III)-resistant lines developed similar infection rates as the wild-type lines during the early-stage infections, but significant differences were observed during the late-stage of the infections. Thus, on day 7 p. i., resistant lines showed lower representation of heavy infections with colonization of the stomodeal valve and lower percentage of metacyclic promastigote forms in comparison to wild-type strains. Observed differences between both resistant lines suggest that the level of Sb(III)-resistance negatively correlates with the quality of the development in the vector. Nevertheless, both resistant lines developed mature infections with the presence of infective metacyclic forms in almost half of infected sandflies. The passage of parasites through the sand fly guts does not significantly influence their capacity to multiply in vitro. The IC50 values and molecular analysis of antimony-resistance genes showed that the resistant phenotype of Sb(III)-resistant parasites is maintained after passage through the sand fly. Sb(III)-resistant lines of L. major MON-25 were able to produce mature infections in Ph. papatasi suggesting a possible circulation in the field using this vector.

Abstract The development of water‐based composite cathode slurries for Li‐ion batteries is hindered by adverse interactions between the battery active material and water. Insights into interactions between H2O and LiNi0.5Mn1.5O4 (LNMO) are studied using a thin‐film model system. The reactivity of this active material with H2O is evaluated at different lithiation states, showing that protonation of the active material in aqueous environments is electrochemically driven, rather than a chemical Li+/H+ ion exchange reaction. The electrochemically driven mechanism describing the protonation of LNMO is only present when the material is in its partially delithiated form. These findings suggest it is possible to cast this material from an aqueous precursor when lithiated, as long as there are no traces of it when the electrochemical delithiation (cell charging) is carried out.

Abstract Dietary restriction (DR) delays aging, but the mechanism remains unclear. We identified polymorphisms in mtd, the fly homolog of OXR1, which influenced lifespan and mtd expression in response to DR. Knockdown in adulthood inhibited DR-mediated lifespan extension in female flies. We found that mtd/OXR1 expression declines with age and it interacts with the retromer, which regulates trafficking of proteins and lipids. Loss of mtd/OXR1 destabilized the retromer, causing improper protein trafficking and endolysosomal defects. Overexpression of retromer genes or pharmacological restabilization with R55 rescued lifespan and neurodegeneration in mtd-deficient flies and endolysosomal defects in fibroblasts from patients with lethal loss-of-function of OXR1 variants. Multi-omic analyses in flies and humans showed that decreased Mtd/OXR1 is associated with aging and neurological diseases. mtd/OXR1 overexpression rescued age-related visual decline and tauopathy in a fly model. Hence, OXR1 plays a conserved role in preserving retromer function and is critical for neuronal health and longevity.

Saline-alkaline lakes often shelter high biomasses despite challenging conditions, owing to the occurrence of highly adapted phototrophs. Dziani Dzaha (Mayotte) is one such lake characterized by the stable co-dominance of the cyanobacterium Limnospira platensis and the picoeukaryote Picocystis salinarum throughout its water column. Despite light penetrating only into the uppermost meter, the prevailing co-dominance of these species persists even in light- and oxygen-deprived zones. Here, a depth profile of phototrophs metatranscriptomes, annotated using genomic data from isolated strains, is employed to identify expression patterns of genes related to carbon processing pathways including photosynthesis, transporters and fermentation. The findings indicate a prominence of gene expression associated with photosynthesis, with a peak of expression around 1 m below the surface, although the light intensity is very low and only red and dark red wavelengths can reach it, given the very high turbidity linked to the high biomass of L. platensis. Experiments on strains confirmed that both species do grow under these wavelengths, at rates comparable to those obtained under white light. A decrease in the expression of photosynthesis-related genes was observed in L. platensis with increasing depth, whereas P. salinarum maintained a very high pool of psbA transcripts down to the deepest point as a possible adaptation against photodamage, in the absence and/or very low levels of expression of genes involved in protection. In the aphotic/anoxic zone, expression of genes involved in fermentation pathways suggests active metabolism of reserve or available dissolved carbon compounds. Overall, L. platensis seems to be adapted to the uppermost water layer, where it is probably maintained thanks to gas vesicles, as evidenced by high expression of the gvpA gene. In contrast, P. salinarum occurs at similar densities throughout the water column, with a peak in abundance and gene expression levels which suggests a better adaptation to lower light intensities. These slight differences may contribute to limited inter-specific competition, favoring stable co-dominance of these two phototrophs.

The significant rise in plastic consumption and waste generation, coupled with the urgent need for sustainable energy solutions, has led to innovative research seeking to convert plastic waste into valuable resources. This review focuses on the application of hydrothermal carbonization as a promising technique for transforming plastic waste into valuable products. It highlights the suitability of hydrothermal carbonization for plastic waste conversion, and presents recent reports showing promising results, prospects, and a range of potential hydrochar applications, including solid recovered fuels, catalysts, direct carbon fuel cells and supercapacitors. This review further presents the challenges in utilizing plastic hydrochar across different applications, which include feedstock variability, contamination, scalability, material properties, and environmental considerations. The need for optimized synthesis methods, stable performance, and long-term sustainability is also emphasized. The critical evaluation of the applications of hydrothermal carbonization can contribute to advancing sustainable waste management and renewable energy production.

Abstract Surface antigenic variation is crucial for major pathogens that infect humans. To escape the immune system, they exploit various mechanisms. Understanding these mechanisms is important to better prevent and fight the deadly diseases caused. Those used by the fungus Pneumocystis jirovecii that causes life-threatening pneumonia in immunocompromised individuals remain poorly understood. Here, though this fungus is currently not cultivable, our detailed analysis of the subtelomeric sequence motifs and genes encoding surface proteins suggests that the system involves the reassortment of the repertoire of ca. 80 non-expressed genes present in each strain, from which single genes are retrieved for mutually exclusive expression. Dispersion of the new repertoires, supposedly by healthy carrier individuals, appears very efficient because identical alleles are observed in patients from different countries. Our observations reveal a unique strategy of antigenic variation. They also highlight the possible role in genome rearrangements of small imperfect mirror sequences forming DNA triplexes.

Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some of them have been found in unaffected controls or relatives. Here, we describe individuals with likely pathogenic variants in KDM5B, including eight individuals with dominant missense variants. This study is a retrospective case series of 21 individuals with variants in KDM5B. We performed deep phenotyping and collected the clinical information and molecular data of these individuals’ family members. We compared the phenotypes according to variant type and to those previously described in the literature. The most common features were developmental delay, impaired intellectual development, behavioral problems, autistic behaviors, sleep disorders, facial dysmorphism, and overgrowth. DD, ASD behaviors, and sleep disorders were more common in individuals with dominant disruptive KDM5B variants, while individuals with dominant missense variants presented more frequently with renal and skin anomalies. This study extends our understanding of the KDM5B-related neurodevelopmental disorder and suggests the pathogenicity of certain dominant KDM5B missense variants.

Climate change and the scarcity of primary resources are driving the development of new, more renewable and environmentally friendly industrial processes. As part of this green chemistry approach, extremozymes (extreme microbial enzymes) can be used to replace all or part of the chemical synthesis stages of traditional industrial processes. At present, the production of these enzymes is limited by the cellular chassis available. The production of a large number of extremozymes requires extremophilic cellular chassis, which are not available. This is particularly true of halophilic extremozymes. The aim of this review is to present the current potential and challenges associated with the development of a haloarchaea-based cellular chassis. By overcoming the major obstacle of the limited number of genetic tools, it will be possible to propose a robust cellular chassis for the production of functional halophilic enzymes that can participate in the industrial transition of many sectors.