Browse Articles

Autophagy Is Required for Dopaminergic Axon Development and Confers Their Responsiveness to Guidance Cues

Midbrain dopamine (mDA) neurons play a wide range of brain functions, but the molecular mechanisms driving the formation of mDA circuits remain largely unknown. Here, we show that autophagy, the main cellular recycling pathway, is present in the growth cones of developing mDA neurons, and its level changes dynamically in response to guidance cues. To characterize the role of autophagy in mDA axon growth and guidance, we knocked out essential autophagy genes (Atg12, Atg5) specifically in mDA neurons in mice of either sex. Autophagy-deficient mDA axons exhibit axonal swellings and reduced branching both in vitro and in vivo. Strikingly, deletion of autophagy-related genes completely blunted the response of mDA neurons to both chemorepulsive and chemoattractive guidance cues. Our data demonstrate that autophagy plays a central role in regulating mDA neuron development by orchestrating axonal growth and guidance.

Survival outcomes with trastuzumab deruxtecan in HER2-positive vs. HER2-low breast cancer patients with brain metastases: a real-world cohort study

Exploring the contribution of straw utilization to carbon emission reduction in Anhui Province (China)

Taking various prefecture-level cities in Anhui Province as the subject of this study, this research draws on data from the ‘Anhui Statistical Yearbook’ to analyze crop straw resources’ potential full utilization, and spatial distribution characteristics, in Anhui Province for the year 2023. The carbon neutralizing effect of straw full utilization was also evaluated using life cycle assessment. Results indicate that the total theoretical straw resources from major crops in Anhui Province in 2023 amounted to 5.213 × 10 7 tons (t), dominated by wheat, rice, and corn straw; which collectively accounted for 89.72% of the total. The carbon emission reductions from straw utilization through fertilization, animal feed, energy generation, substrate application, and raw material processing were approximately 4 × 10 6 , 1.07 × 10 6 , 5.8 × 10 5 , 9.8 × 10 4 , and 1.67 × 10 5 t of CO₂, respectively. Clarifying the total amount, types, potential utilization, and spatial distribution of straw resources at the city level is essential for promoting rational resource allocation and facilitating logicall regional planning for the utilization of those resources. These findings are of paramount importance towards efforts to achieve the goals of “Carbon peaking and carbon neutrality” (Dual-carbon) and fostering coordinated economic and social development in China. Under the framework of “dual carbon” national strategy and the overall layout of agricultural carbon emission reduction, the data analysis results of straw resource utilization in Anhui Province can serve as a reference for other regions to carry out relevant work.

Correction: Biological activity, UHPLC-MS phytochemical profiling, and computational studies of the leaf extract of Acridocarpus socotranus

Sterilization efficacy of a warm-air circulation system in a vaporized hydrogen peroxide sterilizer

Background Vaporized hydrogen peroxide (VH 2 O 2 ) sterilization is a widely recognized method for low-temperature sterilization of medical devices. To overcome limitations associated with residual moisture and maximize sterilization efficacy, the integration of a warm-air circulation system (WACS) is proposed as a robust solution. Objective This study aimed to evaluate the effects of the WACS by comparing temperature uniformity and moisture removal with and without its operation. Additionally, the study assessed whether the WACS contributes to effective sterilization under conditions involving complex medical devices. Methods Temperature variations within the sterilization chamber and medical devices were monitored using sensors. The impact of the WACS on sterilization efficacy was assessed by introducing artificial moisture to the loading packages in cycles performed with and without the system. Sterilization efficacy was assessed through tests with various items, including process challenge devices (PCDs), flexible and rigid lumens, and dual flexible endoscope dummies. Results The WACS maintained a stable temperature of approximately 55 ~ 60 °C and effectively removed moisture throughout sterilization cycles, ensuring successful sterilization of all items. Conclusion This study demonstrates that the WACS significantly improves sterilization effectiveness by ensuring uniform temperature and effective moisture removal. This additional system in the VH 2 O 2 sterilizers will enhance the safety and sterilization efficacy of complex medical devices in healthcare settings.

Swarm intelligence-guided ROI selection for deep learning assessment of HER2 in colorectal cancer

Local genetic correlations between systemic sclerosis and common cancer types

Introduction The incidence of cancer, encompassing all major types, is significantly higher among patients with systemic sclerosis (SSc) compared to the general population. While previous studies have assessed the global genetic relationships between SSc and various cancers and found no evidence of causality or pleiotropy, these methods average effects across the genome and thus ignore potential opposing directional effects at different loci, thereby missing locus-specific associations. To address this gap, we assessed fine-scaled genetic overlap between SSc and commonly associated cancers, namely breast and lung cancers, as well as hematologic malignancies, by applying local genetic correlation analyses. Methods We assessed the genetic relationship between SSc and cancers that frequently co-occur with SSc: breast cancer and its’ four main molecular subtypes: HER2-enriched-like, luminal A and B-like, and triple-negative breast cancers, as well as lung cancer, lymphocytic leukemia, and non-Hodgkin's lymphoma. Published genome-wide association study statistics were obtained from the GWAS catalog and The Breast Cancer Association Consortium, and data were standardized, quality control filtered, and preprocessed. Global and local genetic correlations were evaluated using linkage disequilibrium score regression and Local Analysis of [co]Variant Annotation software. Gene-based cross-trait meta-analysis, colocalization and fine-mapping approaches were used to assess evidence of pleiotropy across regions identified by local genetic correlation analyses. We implemented visualization of the local genetic correlations and functional enrichment analyses of pleiotropic genes from these local correlations. Results We did not detect any significant global genetic correlation between SSc and the analyzed cancer subtypes. However, we identified 23 significant local bivariate correlations; 21 were with different molecular subtypes of breast cancer. However, only the locus shared between SSc and lung cancer showed strong evidence of pleiotropy. Genes within loci shared with lung cancer were involved in cell communication and signaling, extracellular matrix remodelling and skin morphogenesis. Conclusions We report a pleiotropic locus between SSc and lung cancer, illuminating potential pathobiological mechanisms and providing gene candidates for future research.

Delta feature and random forest–enhanced LSTM–attention forecasts with probabilistic postprocessing for rainfall forecasting

When Matilda shows up: The double-edged impact of women researchers’ media visibility in management science

Although the proportion of women in academic positions has increased, women researchers continue to receive less media coverage than their counterparts. To examine the implications of this underrepresentation, we investigate how different audiences respond to women researchers’ increased visibility in social sciences dissemination media. We conducted two laboratory experiments, the first with a sample of non-academic individuals (N = 271) and the second with a sample of graduate students (N = 129). Results show that greater visibility of women researchers reduces the gender gap in self-efficacy beliefs between men and women in both populations. It also increases women researchers’ perceived expertise among non-academic participants, but not among graduate students. Among the later, however, heightened visibility is also unexpectedly associated with a decline in the perceived attractiveness of academic careers, but only for men. While our research focuses specifically on women researchers in the field of management science and manipulates media visibility through the relative representation of women and men in a simulated scientific dissemination newsletter, our findings offer broader insights into how media exposure can influence self-efficacy beliefs, perceptions of researchers’ expertise, and the attractiveness of academic careers. Building on these insights, we propose recommendations for researchers, academic institutions, and media organizations engaged in science dissemination.

ESAK-YOLO: multi-scale attention enhanced object detection for floating waste in complex water scenes

Origin of the Unusual Narrowband Near-Infrared Emission from Cr ³⁺ -Doped Oxides

Exploring the perceived impact of physical activity on physical and mental health among individuals with long COVID: A qualitative interview inquiry

Objectives Long COVID presents a significant health burden with limited treatment options. Physical activity (PA) has been suggested for self-management, yet symptom worsening has been reported in similar patient populations. This study aims to identify PA’s perceived impact on physical and mental health in adults with long COVID. Methods Semi-structured interviews were conducted with 34 adults (mean age 52 years, 62% women) based in the United States (U.S.) self-reporting long COVID. PA-related content was analyzed using deductive thematic analysis, assessing worsened and improved health experiences attributed to PA. Results Participants’ perceived health scores were one standard deviation worse than the general U.S. population. Most participants (64.7%) reported worsening long COVID symptoms with PA, while 14.7% noted improvement. Themes for worsened physical health included post-exertional malaise, specific symptom worsening (e.g., fatigue), limited PA abilities, external control perceptions, forced inactivity, and loss of previous PA abilities. Improved health themes involved beliefs in health benefits, symptom improvement, increased energy, accomplishment, enhanced PA abilities, and hope. Discussion PA’s impact on health varied among individuals with long COVID, highlighting the need to tailor PA recommendations to individual needs and limits.

The power of many small sex differences in cognition, personality, and interests

Abstract It has repeatedly been shown that most psychological sex differences are small, with largely overlapping distributions. This study examined whether multiple small sex differences—across cognitive performance, personality traits, and interests—can collectively distinguish between males and females and predict real-life outcomes. Participants (N F  = 1465, N M  = 1302, 35–45 years old) completed online tests and questionnaires that assessed cognitive performance, personality, and interest in people and in things. Results showed sex differences across 13 tasks and questionnaires in the expected directions. Importantly, when combined, these measures correctly predicted whether an individual was male or female in 80% of cases and accounted for a substantial share of the variance in the real-life outcome of occupational gender segregation. These findings demonstrate how multiple small individual differences can collectively yield substantial predictive power, offering new insight into the underpinnings of gender differences in society.

Motorization and its consequences: A mixed-methods study on the epidemiology, impact, and stakeholder perspectives of road traffic injuries among undergraduate two-wheeler riding students in Nepal

Introduction Motorization has undeniably enhanced mobility and convenience, but it comes at a significant cost, as the increasing number of vehicles has led to a surge in road traffic injuries (RTIs) now a major global cause of disability and death. Over the past decade, the significant growth in two-wheelers has coincided with a rise in RTIs, creating an increasing concern for young individuals. This mixed-method study aims to explore epidemiology, assess their impact on undergraduate students, and gather key recommendations from stakeholders to improve road safety and reduce injury rates. Methodology The quantitative data collection was conducted among undergraduate students in the four colleges in Kathmandu district. The total number of participants in this study was 1217 students of 17–31 years of age. Furthermore, for the qualitative data collection, 5 Key informant interviews were conducted among various stakeholders. Results The prevalence of RTI in 2021–2022 was 23%. The most common injuries were bruises in the upper and lower limbs. It was seen that only 78% of the respondents had a driving license. The injuries led to academic loss and caused financial strain due to healthcare and vehicle repair expenses. 5 key recommendations to decrease the ever-increasing burden of RTI have emerged from the qualitative data analysis. Conclusion The study highlighted a high prevalence and impact of RTIs among undergraduate students along with 5 key recommendations that came forward from this study could be instrumental for road safety in Nepal.

Antibiotic prescriptions in Lombardy Region according to WHO AWaRe classification: trend from 2000 to 2024

A portable, ultra-low cost, open-source, pedal-controlled microinjector for laboratory use

In vivo transduction or electroporation often requires sub-microliter volume injection of virus or recombinant DNA/RNA to a precise anatomic site. Two-hand manual manipulation of the injection needle and target tissues is dramatically faster than mechanical manipulation, but technically challenging for operators. Here, we present an all open-source, footswitch-actuated injector for nano- or microliter volumes. Our microinjector is simple, can be assembled in less than 2 hours with ordinary tools, does not require custom fabrication or soldering, and can cost less than $130 USD. This device is completely self-contained, pressure controllable, and offers both aspirate and discharge modes to facilitate multiple injections during the same procedure. Pulse-triggered discharges can reliably deliver nanoliter volumes with dispense errors of around 15%. By reducing technical and financial barriers, we anticipate this microinjector may inspire adoption of in vivo electroporation or genome editing across broader scientific communities where access may be presently limited.

Insular Input to the Prelimbic Cortex Underlies Social Affective Behavior in Rats

To navigate social interactions, animals must adjust their behavior in response to information derived from conspecifics. The integration of social information and coordination of behavior occurs within a distributed social decision-making network. The prelimbic (PL) prefrontal cortex and the insula (IC) are key nodes in the salience network which is anatomically situated to interact with the social brain. We investigated the IC→PL circuit in a social affective preference (SAP) test in which male rats are exposed to two age-matched conspecifics where one is stressed via footshock and the other is naive to stress. Typically, rats approach stressed juvenile conspecifics but avoid stressed adults. Using a combination of local and tract-specific loss of function methods, we demonstrate that the PL, anterior IC, and the tracts between the posterior or anterior IC and the PL are necessary when rats face the choice to approach or avoid stressed conspecifics. Going further, chemogenetic inhibition of PL neurons innervated by the IC also interfered with social affective behaviors. These studies enrich our understanding of the neurobiology of social decision-making by establishing a mechanistic link between insular and prefrontal circuits.

Gene deletion of Klotho in the dentate gyrus does not affect the number of adult-born granule cells

Abstract Overexpression and exogenous administration of the anti-ageing hormone Klotho has been shown to enhance and promote adult hippocampal neurogenesis. However, whether locally produced Klotho from dentate gyrus neurons contributes to this process has remained unclear. Here we show that conditional gene knockout of Klotho in granule cells of the mouse dentate gyrus results in a temporally restricted reduction of immature neurons (days 7–17 post-mitosis), but does not affect stem cell proliferation or long-term neuronal survival. Thus, the role of local Klotho expression is not essential for functional maturation and integration of adult-born neurons.

Limited and idiosyncratic thermal acclimation in soil saprotrophic fungi

Increased soil microbial activity due to higher temperatures caused by heatwaves could lead to higher carbon losses from soil into the atmosphere, further accelerating climate change. Hence, knowing how soil microbes respond to higher temperatures is crucial for improving soil-atmosphere carbon circulation models in the context of climate change. Thermal acclimation may reduce carbon losses from soils by retarding increases in microbial activity in response to elevated temperatures. However, the capacity of soil microbes to acclimate to realistic soil temperatures in vitro, and our ability to predict this acclimation based on traits, remains poorly understood. We tested how submission to two previous temperature treatments or ‘environmental histories’ affected subsequent growth at two exposure temperatures for seven widespread soil saprotrophic fungi. We hypothesized that (1) soil fungi have higher intrinsic growth and weaker self-limitation after exposure to a colder environmental history, and (2) the response of fungal eco-physiological traits (pigmentation and spore load) to elevated temperature exposure predicts fungal acclimation in terms of growth. Our results showed that environmental history had limited impact on the tested fungi, and trait responses to history temperatures did not predict fungal growth after treatment with both history and exposure temperatures. We conclude that fungal thermal acclimation is limited and idiosyncratic.

Mechanism of age-related accumulation of mtDNA mutations in human blood

Abstract Accumulation of mutant mitochondrial DNA (mtDNA) heteroplasmy is among the strongest signatures of ageing 1 . Here we investigated the underlying mechanism by calling mtDNA sequence, mtDNA abundance and mtDNA heteroplasmic variants in human blood using whole-genome sequences from approximately 750,000 individuals. We observed that mtDNA single-nucleotide variants (mtSNVs) accumulate sharply at age 60 years, occur at low levels of heteroplasmy, exhibit little evidence of positive selection and are likely to be predominantly neutral. The mutational spectrum of mtSNVs does not reflect oxidative lesions, as is commonly invoked, but is more consistent with mtDNA replication errors. To understand why mtSNVs become detectable with age, we performed a genome-wide association study for heteroplasmic mtSNV burden, identifying germline variants near TERT , TCL1A and SMC4 , all of which have been linked to clonal haematopoiesis (CH) 2 . Rare-variant analysis also showed that high mtSNV burden is associated with mutations in numerous CH driver genes. These genetic associations persisted even after exclusion of individuals with known CH driver mutations. Our results support a model in which ‘cryptic’ mtDNA mutations initially arise randomly as replication errors but are undetectable in bulk. They then become apparent only through age-related expansion of cellular clones in blood. We propose that the high copy number and mutation rate of mtDNA make it a sensitive blood-based marker of somatic mosaicism due to CH. Our work mechanistically unifies three prominent signatures of ageing: common germline variants in TERT , CH and observed accrual of mtDNA mutations.