Search

Abstract Holobionts are highly organized assemblages of eukaryotic hosts, cellular microbial symbionts, and viruses, whose interactions and evolution involve complex biological processes. It is largely unknown which specific determinants drive similarity or individuality in genetic diversity between holobionts. Here, we combine short- and long-read sequencing and DNA-proximity-linkage technologies to investigate intraspecific diversity of the microbiomes, including host-resolved viruses, in individuals of a model marine sponge. We find strong impacts of the sponge host and the cellular hosts of viruses on strain-level organization of the holobiont, whereas substantial overlap in nucleotide diversity between holobionts suggests frequent exchanges of microbial cells and viruses at intrastrain level in the local sponge population. Immune-evasive arms races likely restricted virus-host co-evolution at the intrastrain level, generated holobiont-specific genome variations, and linked virus-host genetics through recombination. Our work shows that a decoupling of strain- and intrastrain-level interactions is a key factor in the genetic diversification of holobionts.

Abstract Liver metastasis remains the primary cause of mortality in patients with colon cancer. Identifying specific driver gene mutations that contribute to metastasis may offer viable therapeutic targets. To explore clonal evolution and genetic heterogeneity within the metastasis, we conducted single-cell exome sequencing on 150 single cells isolated from the primary tumor, liver metastasis, and lymphatic metastasis from a stage IV colon cancer patient. The genetic landscape of the tumor samples revealed that both lymphatic and liver metastases originated from the same region of the primary tumor. Notably, the liver metastasis was derived directly from the primary tumor, bypassing the lymph nodes. Comparative analysis of the sequencing data for individual cell pairs within different tumors demonstrated that the genetic heterogeneity of both liver and lymphatic metastases was also greater than that of the primary tumor. This finding indicates that liver and lymphatic metastases arose from clusters of circulating tumor cell (CTC) of a polyclonal origin, rather than from a single cell from the primary tumor. Single-cell transcriptome analysis suggested that higher EMT score and CNV scores were associated with more polyclonal metastasis. Additionally, a mutation in the TRPS1 (Transcriptional repressor GATA binding 1) gene, TRPS1 R544Q, was enriched in the single cells from the liver metastasis. The mutation significantly increased CRC invasion and migration both in vitro and in vivo through the TRPS1R544Q/ZEB1 axis. Further TRPS1 mutations were detected in additional colon cancer cases, correlating with advanced-stage disease and inferior prognosis. These results reveal polyclonal seeding and TRPS1 mutation as potential mechanisms driving the development of liver metastases in colon cancer.

Abstract Background In 2022, our team launched the pioneering national proficiency testing (PT) scheme for the pathological diagnosis of breast cancer, rapidly establishing its credibility throughout China. Aiming to continuously monitor and improve the proficiency of Chinese pathologists in breast pathology, the second round of the PT scheme was initiated in 2023, which will expand the number of participating institutions, and will conduct a nationwide investigation into the interpretation of HER2 0, 1+, and 2+/FISH- categories in China. Methods The methodology employed in the current round of PT scheme closely mirrors that of the preceding cycle in 2022, which is designed and implemented according to the “Conformity assessment—General requirements for proficiency testing”(GB/T27043—2012/ISO/IEC 17043:2010). More importantly, we utilized a statistics-based method to generate assigned values to enhance their robustness and credibility. Results The final PT results, published on the website of the National Quality Control Center for Cancer ( http://117.133.40.88:3927 ), showed that all participants passed the testing. However, a few institutions demonstrated systemic biases in scoring HER2 0, 1+, and 2+/FISH- with accuracy levels below 59%, considered unsatisfactory. Especially, the concordance rate for HER2 0 cases was only 78.1%, indicating challenges in distinguishing HER2 0 from low HER2 expression. Meanwhile, areas for histologic type and grade interpretation improvement were also noted. Conclusions Our PT scheme demonstrated high proficiency in diagnosing breast cancer in China. But it also identified systemic biases in scoring HER2 0, 1+, and 2+/FISH- at some institutions. More importantly, our study highlighted challenges in the evaluation at the extreme lower end of the HER2 staining spectrum, a crucial area for further research. Meanwhile, it also revealed the need for improvements in interpreting histologic types and grades. These findings strengthened the importance of robust quality assurance mechanisms, like the nationwide PT scheme conducted in this study, to maintain high diagnostic standards and identify areas requiring further training and enhancement.

Abstract Background This study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting. Methods This was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients. Conclusions Rh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

Abstract As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran’s index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input–output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management.

Abstract People procrastinate, but why? One long-standing hypothesis is that temporal discounting drives procrastination: in a task with a distant future reward, the discounted future reward fails to provide sufficient motivation to initiate work early. However, empirical evidence for this hypothesis has been lacking. Here, we used a long-term real-world task and a novel measure of procrastination to examine the association between temporal discounting and real-world procrastination. To measure procrastination, we critically measured the entire time course of the work progress instead of a single endpoint, such as task completion day. This approach allowed us to compute a fine-grained metric of procrastination. We found a positive correlation between individuals’ degree of future reward discounting and their level of procrastination, suggesting that temporal discounting is a cognitive mechanism underlying procrastination. We found no evidence of a correlation when we, instead, measured procrastination by task completion day or by survey. This association between temporal discounting and procrastination offers empirical support for targeted interventions that could mitigate procrastination, such as modifying incentive systems to reduce the delay to a reward and lowering discount rates.

Abstract Vitamin D deficiency is common in patients with inflammatory bowel disease (IBD). In this study, we aimed to evaluate the prevalence and risk factors of vitamin D deficiency in a Taiwanese IBD cohort. Vitamin D levels were checked in adult patients with IBD who were treated at Changhua Christian Hospital, a medical center in central Taiwan, from January 2017 to December 2023. The risk factors for vitamin D deficiency were evaluated. 106 adult IBD patients were included, including 20 patients with Crohn’s disease and 86 with ulcerative colitis. The median age at diagnosis was 39.2 years. The mean vitamin D level was 22.2 ± 8 ng/mL. Forty-five patients (42.5%) had vitamin D deficiency (vitamin D level

Abstract Magnetic skyrmions are topological spin textures that are regarded as promising information carriers for next-generation spintronic memory and computing devices. For practical applications, their deterministic generation, manipulation, and efficient detection are the most critical aspects. Although the generation and manipulation of skyrmions have been extensively studied, efficient electrical detection of mobile skyrmions by using techniques that are compatible with modern magnetic memory technology, remains to be adequately addressed. Here, through integrating magnetic multilayers that host nanoscale skyrmions, together with the magnetic tunnel junctions (MTJ), we demonstrate the electrical detection of skyrmions by using the tunneling magnetoresistance (TMR) effect with a TMR ratio that reaches over 100% at room temperature. By building prototype three-terminal racetrack-like devices, we further show the electrical detection of mobile skyrmions by recording the time-dependent TMR ratios. Along with many recent developments, our results could advance the development of skyrmionic memory and logic devices.

This study analyzes the influences of evapotranspiration or substrate moisture variation on the indoor-temperature reduction of green roofs compared to the control group. A multiple linear regression (MLR) model for the operation stage based on observation and an integrated MLR model for the planning stage based on simulation are verified. The MLR model shows 0.64 °C of the Root Mean Square Error (RMSE) in predicting the hourly difference of temperature reduction based on the measured change in evapotranspiration and air temperature. The contributions of the hourly increment of air temperature (ΔTa) and increment of evapotranspiration (ΔET) are similar to the hourly increment of temperature reduction (ΔTdif). Then, the feasibility of the integrated MLR model is demonstrated based on the evapotranspiration and substrate moisture of a green roof simulated by a hydrological model as well as the indoor-temperature reduction simulated by a building energy model, which has fair performances in capturing the heat-transfer and water-balance physical process within a green roof. The integrated MLR model shows that evapotranspiration is relatively essential, followed by substrate moisture, air temperature, and vapor pressure. Despite the modeling bias, the integrated model quantitatively relates the influential factors to temperature reduction and predicts temperature reduction with an RMSE of 1.02 °C. The integrated model can quantify the influence of irrigation on temperature reduction under various climate conditions and green roof structures. This study demonstrates the procedure of establishing the integrated model. It shows the potential of the integrated model to provide decision support on irrigation for multi-purpose optimization of green roof performances.

IntroductionLung cancer is a major global health concern. Patients undergo a substantial process of emotional transformation following a lung cancer diagnosis, during which subtle changes in brain function and/or structure may occur. As such, the present study aimed to investigate the neuroplastic changes induced by negative emotions in patients with early-stage lung cancer.MethodsThis cross-sectional study recruited 35 patients with early-stage lung cancer and 33 age- and sex-matched healthy control patients. All participants completed the Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD), and functional magnetic resonance imaging (fMRI). Amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used as the fMRI indices. Correlations between the clinical assessments and ALFF and ReHo values were calculated.ResultsOur analysis revealed no significant differences in HAMD and HAMA scores between patients and control patients (p > 0.05). However, significant alterations in ALFF and ReHo were observed in multiple brain regions in patients with early-stage lung cancer compared to healthy controls (PFalseDiscoveryRate < 0.05). Specifically, ALFF values were decreased in the right postcentral gyrus, calcarine, and left middle cingulate, while ReHo values increased in the right angular gyrus and decreased in the bilateral postcentral gyrus, insula, left calcarine, putamen, superior temporal gyrus, middle cingulate, and right Rolandic gyrus. The HAMD score was significantly correlated with the ALFF value in the right postcentral gyrus (P = 0.007).ConclusionThis study provides valuable insights into the adaptive responses of the brain following the early diagnosis of lung cancer, revealing potential disturbances in negative emotional processing. Harnessing neuroplasticity may open new avenues for the establishment of personalized treatment strategies and targeted interventions to support the emotional and mental health of patients with lung cancer.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host–symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill’s structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host–symbiont interaction and the bivalves' environmental adaption mechanisms.

Urban green infrastructure (UGI) is pivotal in reconciling biodiversity conservation with sustainable urban development through adaptive management approaches. This paper introduces a comprehensive conceptual framework integrating ecological principles, urban planning strategies, and adaptive management methodologies to nurture resilient and biodiverse urban landscapes. The essence of UGI lies in its capacity to bolster ecological connectivity, restore ecosystem functions, and provide habitats for diverse flora and fauna within urban settings. Fundamental principles governing UGI design underscore its multifunctionality, connectivity, diversity, and accessibility, emphasizing the importance of adaptive management marked by its iterative and participatory nature. Despite challenges posed by urbanization, such as habitat loss, pollution, and climate change, UGI interventions offer promising avenues for enhancing habitat quality, connectivity, and ecosystem resilience. Global case studies demonstrate the effectiveness of UGI in biodiversity conservation, leveraging initiatives like green roofs, urban forests, and community gardens. UGI significantly contributes to sustainable urban development by offering diverse ecosystem services across various domains. Adaptive management is critical for effective UGI planning and implementation, ensuring flexibility amidst evolving environmental conditions. However, UGI encounters hurdles, including funding constraints, institutional fragmentation, and equity issues. Addressing these challenges necessitates innovative financing mechanisms, community involvement, and policy innovations. UGI presents a transformative pathway towards fostering resilient, biodiverse, and sustainable urban landscapes, imperative for cities to thrive in the 21st century.