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Conventional ultrafine-grains can generate high strength in Mg alloys, but significant tradeoff of corrosion resistance due to inclusion of a large number of non-equilibrium grain boundaries. Herein, an ultrafine-grain structure consisting of dense ultrafine twins is prepared, yielding a high strength up to 469 MPa and decreasing the corrosion rate by one order of magnitude. Generally, the formation of dense ultrafine twins in Mg alloys is rather difficult, but a carefully designed multi-directional compression treatment effectively stimulates twinning nucleation within twins and refines grain size down to 300 nm after 12-passes compressions. Grain-refinement by low-energy twins not only circumvents the detrimental effects of non-equilibrium grain boundaries on corrosion resistance, but also alters both the morphology and distribution of precipitates. Consequently, micro-galvanic corrosion tendency decreases, and severe localized corrosion is suppressed completely. This technique has a high commercial viability as it can be readily implemented in industrial production. Conventional ultrafine grains can generate high-strength Mg alloys, but non-equilibrium grain boundaries deteriorates their corrosion resistance. Here, the authors present ultrafine grained Mg alloys with dense twins that display high strength and reduced corrosion rate by one order of magnitude.

Plasticity of neoplasia, whereby cancer cells attain stem-cell-like properties, is required for disease progression and represents a major therapeutic challenge. We report that in breast cancer cells NANOG , SNAIL and NODAL transcripts manifest multiple isoforms characterized by different 5’ Untranslated Regions (5’UTRs), whereby translation of a subset of these isoforms is stimulated under hypoxia. The accumulation of the corresponding proteins induces plasticity and “fate-switching” toward stem cell-like phenotypes. Mechanistically, we observe that mTOR inhibitors and chemotherapeutics induce translational activation of a subset of NANOG , SNAIL and NODAL mRNA isoforms akin to hypoxia, engendering stem-cell-like phenotypes. These effects are overcome with drugs that antagonize translational reprogramming caused by eIF2α phosphorylation (e.g. ISRIB), suggesting that the Integrated Stress Response drives breast cancer plasticity. Collectively, our findings reveal a mechanism of induction of plasticity of breast cancer cells and provide a molecular basis for therapeutic strategies aimed at overcoming drug resistance and abrogating metastasis. Protein synthesis suppression protects breast cancer cells from clinically relevant stresses like hypoxia. Here, the authors show that unique mRNA isoforms that govern stem cell-like phenotypes escape translational repression to drive tumor progression and chemoresistance.

Frailty and sarcopenia are geriatric syndromes of increasing concern and are associated with adverse health outcomes. They are more prevalent among long-term care facility (LTCF) users than among community dwellers. Exercise, especially multicomponent and progressive resistance training, is essential for managing these conditions. However, LTCFs, particularly in rural areas, face challenges in implementing structured exercise programs due to health care professional shortages. Moreover, older adults often become bored with repetitive exercise training and may lose interest over time. The Nintendo Switch Ring Fit Adventure (RFA) exergame is a novel exergame that combines resistance, aerobic, and balance exercises and offers a potential solution by boosting motivation in an immersive manner and reducing staff intervention needs. We aimed to evaluate the clinical effectiveness of an exergame-based exercise training program delivered via RFA (exergame-RFA) in improving muscle mass and functional performance among older adult LTCF users. This was a randomized controlled trial conducted from August 2022 to September 2023 and involved older adult LTCF users (aged ≥60 y) in rural southern Taiwan. Participants were randomized into an intervention group (exergame-RFA plus standard care) or a control group (standard care alone). The intervention, conducted seated with arm fit skills and trunk control exercises using the RFA, lasted 30 minutes twice weekly over 12 weeks. The primary outcomes measured were the Study of Osteoporotic Fractures index (serving as an indicator of frailty status) and the diagnostic criteria for sarcopenia (appendicular skeletal muscle mass index, handgrip strength, and gait speed). The secondary outcomes included functional performance (box and block test as well as maximum voluntary isometric contraction of the dominant upper extremity), muscle condition (muscle thickness measured using ultrasonography), activities of daily living (Kihon checklist), health-related quality of life (Short Form Health Survey-36), and cognitive function (brain health test). We used an intention-to-treat analysis, incorporating a simple imputation technique in statistical analysis. A mixed ANOVA, with time as a within-participant factor and intervention as a between-participant factor, was used to compare the training effects on outcomes. We recruited 96 individuals, of whom 60 (62%) underwent randomization. Of these 60 participants, 55 (92%) completed the study. Significant group×time interactions were observed in the intervention group in all primary outcomes (all P<.001, except P=.01 for handgrip strength) and most secondary outcomes, including maximum voluntary isometric contraction of the biceps (P=.004) and triceps brachii (P<.001) muscles, biceps muscle thickness measured using ultrasonography (P<.001), box and block test (P<.001), Kihon checklist (physical function: P=.01, mood status: P=.003, and total: P=.003), and brain health test (P<.001). The exergame-RFA intervention significantly improved muscle mass, strength, and functional performance among older adult users of rural LTCFs, offering a novel approach to addressing frailty and sarcopenia. ClinicalTrials.gov NCT05360667; https://clinicaltrials.gov/study/NCT05360667. RR2-10.3389/fmed.2022.1071409.

Bronze vessels were the ultimate emblems of power in ancient China. Beginning in the twelfth century, the rediscovery of ancient bronzes as evidence of an earlier golden age led to a revival of bronze casting. This publication presents a comprehensive study of these later Chinese bronzes in archaic styles, which were commissioned by emperors and officials from the twelfth through the nineteenth centuries to assert political legitimacy and alignment with traditional values. Redressing the misconception that these works were mere imitations of the ancient vessels they emulated, 'Recasting the Past' demonstrates that they were in fact creative reinterpretations of antique shapes and decorative motifs that were fundamentally new creations with their own aesthetic and functional character.

All-polymer solar cells (all-PSCs) based on polymerized small molecular acceptors (PSMAs) have made significant progress recently. Here, we synthesize two A-DA’D-A small molecule acceptor based PSMAs of PS-Se with benzo[c][1,2,5]thiadiazole A’-core and PN-Se with benzotriazole A’-core, for the studies of the effect of molecular structure on the photovoltaic performance of the PSMAs. The two PSMAs possess broad absorption with PN-Se showing more red-shifted absorption than PS-Se and suitable electronic energy levels for the application as polymer acceptors in the all-PSCs with PBDB-T as polymer donor. Cryogenic transmission electron microscopy visualizes the aggregation behavior of the PBDB-T donor and the PSMA in their solutions. In addition, a bicontinuous-interpenetrating network in the PBDB-T:PN-Se blend film with aggregation size of 10~20 nm is clearly observed by the photoinduced force microscopy. The desirable morphology of the PBDB-T:PN-Se active layer leads its all-PSC showing higher power conversion efficiency of 16.16%. Through development of non-fullerene acceptors, OPVs have reached efficiencies of 18%, yet the inadequate operational lifetime still poses a challenge for the commercialisation. Here, the authors investigate the origin of instability of NFA solar cells, and propose some strategies to mitigate this issue.

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to α-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1–RSK2–ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA . Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations. Cancer cells rely on glutamine to replenish the TCA cycle. Here, the authors show that oncogenic PIK3CA mutations drive this metabolic rewiring in colorectal cancer cells by up-regulating glutamate pyruvate transaminase expression, thus increasing sensitivity to glutamine starvation.