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PTP1B inhibition promotes microglial phagocytosis in Alzheimer’s disease models by enhancing SYK signaling

Amyloid β (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD). Emerging evidence suggests that impaired microglial Aβ phagocytosis is a key feature in AD, highlighting the therapeutic potential of enhancing this innate immune function. Here, we demonstrate that genetic deletion or pharmacological inhibition of protein tyrosine phosphatase 1B (PTP1B) ameliorated memory deficits and reduced Aβ burden in APP/PS1 mice. Moreover, we show that PTP1B was highly expressed in microglia, and its deficiency promoted a transcriptional shift toward immune activation and phagocytosis. Consistently, PTP1B deletion in microglia enhanced phagocytosis and energy metabolism, supported by increased AKT-mTOR signaling, a pathway essential for meeting the energy demands of activation. Mechanistically, we identified spleen tyrosine kinase (SYK), a key regulator of microglial phagocytosis, as a direct substrate of PTP1B. Inhibition of SYK showed that PTP1B modulates microglial activation in a SYK-dependent manner. These findings established PTP1B as a critical modulator of microglial activation and a potential therapeutic target for AD.

Turmeric essential oil infused pectin blended sodium alginate polymer as sustainable food packaging material

Health-focused frames mobilize Americans to action to address LGBTQ inequality

“More than 1 in 8 LGBTQ people live in states where doctors can refuse to treat them.” This headline describes a flurry of laws passed in 2025 allowing doctors to refuse treatment of LGBTQ patients based on personal beliefs. This and other laws like it limit healthcare access and exacerbate health inequality for LGBTQ individuals. But health is not the only domain in which LGBTQ individuals face disparities. Long-standing inequalities also exist in other domains of life, for example, gay men earn up to 32% less wages than their heterosexual peers. In the current research, we ask if exposure to LGBTQ inequality in one domain (e.g., health) motivates more support for action than exposure to inequality in other domains (e.g., economics). In six experiments (five preregistered), we test our hypothesis that emphasizing health-based LGBTQ inequality (vs. economics and belonging) spurs engagement with and support for mitigating action (S1-2). We also investigate why people support action (S1a-1b) and what boosts support (S3a-3c). As predicted and preregistered, we find greater support for action to mitigate health-based LGBTQ inequality, compared to economics and belonging. This occurs, in part, because people blame LGBTQ individuals less for health (vs. economic) disparities and perceive health inequalities to violate morally sacred values, which is associated with greater perceived injustice. Finally, we find that connecting economic inequality to health inequality in individuals’ minds can increase support for mitigating economic inequality.

The impact of COVID-19 on women’s mental health and coping during pregnancy and postpartum

Abstract The COVID-19 pandemic resulted in elevated rates of depression and anxiety among people during pregnancy, at rates higher than those observed in pregnant populations pre-pandemic. In this mixed methods study, 20 postpartum women were interviewed and administered depression and anxiety screeners to assess the mental health impacts of giving birth during the pandemic. Qualitative data were analyzed using a thematic approach, with subgroups comparisons to draw out differences in emotional, social, and psychological impacts, as well as coping mechanisms used. Descriptive statistics were used to describe the prevalence of anxiety and depressive symptoms. Most women held advanced degrees (85%), were married (95%), first-time parents (60%) and experienced a high-risk pregnancy (60%). Less than half (40%) of the women identified as a racial or ethnic minority. Women in this sample reported low rates of mild anxiety (30%) and depressive symptoms (15%). This study identified three themes related to mental health and coping during pregnancy and postpartum: isolation and loneliness as a result of COVID-19 disruptions, fear and anxiety resulting from simultaneous information overload and uncertainty surrounding COVID-19, and coping mechanisms to confront stress, anxiety, and loneliness. Community-based interventions to promote maternal mental health are needed to complement clinical support and resources.

Harnessing hemostasis to transform surgical scars into CAR-T immunological niches

A reliable and holistic approach to evaluating hearing and cognitive auditory processing in adult and aged companion dogs

Direct preference optimization-based adaptive control for minimizing total harmonic distortion in photovoltaic-powered electric drives

Proximity-driven acceleration of challenging solid-phase peptide couplings

Many important solid-phase synthesis reactions proceed slowly and inefficiently, for example, the coupling of an activated ester to a sterically hindered, bead-displayed amine, a critical step in the synthesis of many peptides. Forcing conditions are often required to achieve acceptable yields. We show here that such reactions can be accelerated by tethering to the bead a nucleophilic pyridine catalyst, which reacts with the activated ester, creating a high local concentration of a reactive acylpyridinium intermediate that couples efficiently to the bead-displayed amine. In many cases, the “cleanliness” of reactions carried out on resins equipped with an immobilized catalyst is substantially better than the analogous reactions in which the catalyst is added to the solution.

Foreign object detection on photovoltaic panels based on DHLNet

Correction for Curtis et al., Fragmentation signatures in cancer patients resemble those of patients with vascular or autoimmune diseases

Sharp Lyapunov inequalities and the emergence of chaos in discrete fractional systems

RPA-independent activation of the ATR/CHK1 pathway

The ATR/CHK1 pathway governs a crucial intra-S-phase checkpoint that safeguards genome stability under replication stress by stabilizing stalled replication forks and ensuring high-fidelity DNA replication. Traditionally, activation of this pathway is thought to rely on replication protein A (RPA)-coated single-stranded DNA, which recruits the ATR–ATRIP complex to sites of stalling fork, positioning RPA as essential for ATR signaling. In this study, we report a surprising and previously unrecognized phenomenon: acute depletion of RPA2 triggers robust ATR/CHK1 activation through an RPA-independent mechanism. Using 293A and RPE-1 cells engineered with an inducible RPA2-dTAG degron system, we observed increased phosphorylation of CHK1 at Ser296 and Ser345 in the absence of RPA. Notably, this elevated CHK1 phosphorylation was abolished by ATR inhibition, confirming its dependence on ATR kinase activity. Mechanistic analyses further revealed that this RPA-independent activation requires the checkpoint mediators RAD9 and TOPBP1. These findings uncover dual mechanisms, both RPA-dependent and -independent, of ATR/CHK1 pathway activation, highlighting a robust and flexible replication stress response network that preserves genome integrity even when canonical signaling is disrupted.

Advanced polymer-based humidity sensor for aerospace applications implementing ZnO-G: theoretical and experimental study

Reply to Compton et al.: Another paradoxical misunderstanding

Multimodal large language models challenge NEJM image challenge

Deglacial stratification of the polar Southern Ocean

It is widely accepted that meltwater from northern ice sheets drove changes in the Atlantic Meridional Overturning Circulation, impacting global climate. In contrast, data are lacking on the Antarctic Ice Sheet’s (AIS) effect on Southern Ocean overturning, despite the Southern Ocean’s central role in ventilating the ocean interior. Here, we present diatom-bound nitrogen isotope evidence indicating that during deglaciations, as wind-driven upwelling in the open Antarctic Ocean increased, AIS melting strengthened density stratification in the polar Antarctic Ocean. This change coincides with reconstructions of meltwater discharge and resembles model simulations of global warming including AIS meltwater forcing. The transient input of freshwater and, thus, buoyancy weakened Southern Ocean’s “lower cell” that outcrops in the polar Antarctic Ocean even as open Antarctic Ocean’s “upper cell” strengthened. Given evidence that deep-ocean ventilation and CO 2 release were ongoing early in deglaciation, our data suggest that the open Antarctic Ocean, and not solely the most polar Antarctic Ocean, can directly ventilate the deep ocean. During the last deglaciation, the strongest density stratification in the polar Antarctic Ocean occurred just before the Antarctic Cold Reversal, when southern hemisphere warming paused and the northern hemisphere warmed sharply (i.e., during the Bølling–Allerød period). We propose that when combined with stronger wind-driven upwelling, the freshwater-driven redirection of upwelled water away from deep water formation and toward the upper cell deepened the global pycnocline, working to restart North Atlantic deep water formation in the Bølling–Allerød period. If so, polar ocean freshening in both hemispheres drove the “bipolar seesaw” events of deglaciation.

Effects of cold plasma generated ozone on development of Galleria mellonella induced alterations in hemolymph protein and biochemistry of beeswax

Abstract Greater wax moth Galleria mellonella is a serious pest in apiculture, invading honeybee colonies and inflicting widespread damage. Ozone gas generated by the non-thermal atmospheric pressure plasma produced with a dielectric barrier discharge (DBD) reactor is an attractive solution for insect control. The effect of ozone gas generated by cold plasma on the egg, larva, and pupae stages of G. mellonella was investigated by using two concentrations, 400 and 800 ppmv, at different exposure times of 5, 10, 20, 40, 60, and 80 min. The mortality rate of the larvae increased as the exposure time lengthened, while a decrease in adult survivorship was observed after exposure. Complete suppression of the survived larval instar percentage and pupation percentage was noted after 7 days of exposure to 40 and 20 min at 400 and 800 ppmv of ozone, respectively, compared to the control group, which had a 96.67% survivorship. Pupal exposure to 800 ppmv for 20 min was sufficient to completely inhibit adult emergence. Larvae exhibited greater tolerance to ozone gas generated by cold plasma than eggs and pupae 24 h after exposure. Additionally, ozone treatment at 400 and 800 ppmv significantly increased total hemolymph protein content after 24 h, reaching 17.55 g/L and 18.50 g/L, respectively, compared to 16.52 g/L for the control. Cold plasma ozone treatment altered the stored beeswax matrix by modifying essential hydrocarbons and enhancing fatty acid diversity, while preserving the fundamental ester structure, thus converting it into a functionally changed biomaterial. Exposure to ozone gas at 800ppmv caused remarkable abnormalities in appearance in wax moths throughout their life stages, resulting in shrunken, twisted, and crippled insects unable to complete normal development.

For reducing premature adult mortality in India, education matters more than income

Preventing premature death is a global policy objective reflected in the SDGs. While numerous studies have found socioeconomic factors to be significantly associated with premature death everywhere in the world, the debate on the relative effect of such factors on mid-age (15 to 59 ages) has not received enough attention, particularly in low-income countries, where this question is pertinent due to scant resources in the healthcare sector. Using nationally representative, longitudinal data from the India Human Development Survey, we assess the relative importance of individual- and community-level education vs. income and wealth in India, where approximately 3 million premature deaths occur annually in mid-ages. We find a clear downward gradient in mid-age mortality with increasing education within each wealth category, whereas no consistent mortality advantage with increasing wealth status is visible within education subgroups. Multilevel logistic regression models show that the decline in the risk of death across the education spectrum by far exceeds (14% for male and 13% for female) the decline moving along the wealth distribution, even after controlling for other relevant demographic, socioeconomic, regional variables. Along with the direct effect of individual-level educational attainment, we also find a protective effect of education at the community level, particularly for women. Based on these findings, we infer that educational attainment is essential for reducing mid-age mortality in India. Population and health policies in developing countries, therefore, should focus on education to prevent adult mortality.

A novel adaptive neuro-fuzzy and adaptive proportional resonant control scheme for PMSM based electric vehicle applications

Neuron-specific modulation of SLC30A10 identifies dopaminergic and glutamatergic neurons as targets of manganese-induced motor disease

Essential metals accumulate in the basal ganglia at elevated levels and induce incurable motor disease. But, unlike other motor diseases, the neuronal targets of essential metals are unknown, and this fundamental knowledge gap has limited therapeutic progress. Because metal efflux transporters have high specificity, we hypothesized that neuron-specific knockout or knockin (i.e., overexpression) of efflux transporters may alter metal levels in targeted neurons and define the neuronal targets of metal-induced disease. To test this, we focused on manganese (Mn)-induced motor disease, which is a public health problem. We generated six neuron-specific Slc30a10 mouse strains with knockout or knockin of the Mn efflux transporter Slc30a10 in dopaminergic, GABAergic, or glutamatergic neurons. In the knockout strains, SLC30A10 was depleted and Mn levels were elevated in targeted brain regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockouts developed motor deficits without Mn exposure. Conversely, in the knockins, SLC30A10 was elevated and the increase in Mn levels after Mn exposure was attenuated in targeted regions. However, only dopaminergic- or glutamatergic-, but not GABAergic-, specific knockins were protected against Mn-induced motor deficits. Dopaminergic-specific Slc30a10 knockouts also exhibited deficits in dopaminergic neurotransmission that were consistent with their motor phenotype. Overall, 1) elevated Mn targets dopaminergic and glutamatergic neurons to induce motor disease, and 2) neuron-specific knockout/knockin of efflux transporters is an effective strategy to isolate the neuronal targets and underlying mechanisms of metal-induced neurological disease.