Driver-response relationships in a large shallow lake since the Anthropocene: Short-term abrupt perturbations versus long-term sustainable.

Lakes, as integral social-ecological systems, are hotspots for exploring climatic and anthropogenic impacts, with crucial pathways revealed by continuous sediment records. However, the response of multi-proxies in large shallow lakes to typical abrupt events and sustained drivers since the Anthropocene remains unclear. Here, we explored the driver-identification relationships between multi-proxy peaks and natural and anthropogenic events as well as the attribution of short-term perturbations and long-term pressures. To this end, sediment core records, socio-ecological data, and documented events from official records were integrated into a large shallow lake (Dongting Lake, China). Significant causal cascades and path effects (goodness-of-fit: 0.488; total effect: -1.10; p < .001) were observed among catchment environmental proxies, lake biogenic proxies, and mixed-source proxies. The peak-event identification rate (PEIR) and event-peak driving rate were proposed, and values of 28.57%-46.43% and 50%-81.25% were obtained, respectively. The incomplete accuracy of depicting event perturbations using sediment proxies was caused by various information filters both inside and outside the lake. PEIRs for compound events were 1.41 (±0.72) and 1.09 (±0.46) times greater than those for anthropogenic-dominated and natural-dominated events, respectively. Furthermore, socio-economic activity, hydrologic dynamics, land-use changes, and agriculture exerted significant and persistent pressures, cumulatively contributing 55.3%-80.9% to alterations in sediment proxies. Relatively synergistic or antagonistic trends in temporal contributions of these forces were observed after 2000, which were primarily attributed to the "Grain for Green" project and the Three Gorges Dam. This study represents one of the few investigations to distinguish the driver-response relationship of multiple proxies in large shallow lakes under typical event perturbations and long-term sustained pressures since the Anthropocene. The findings will help policymakers and managers address ecological perturbations triggered by climate change and human activities over long-term periods.

Coupled effects of human activities and river-Lake interactions evolution alter sources and fate of sedimentary organic carbon in a typical river-Lake system.

Interconnected river-lake systems record sedimentary organic carbon (OCsed) dynamics and watershed environmental changes, providing valuable information for global carbon budgets and watershed management. However, owing to the evolving river-lake interactions under global change, monitoring OCsed is difficult, thereby impeding the understanding of OCsed transport and fate. This study provided new insights into the dynamical mechanisms of OCsed in a typical river-lake system consisting of Dongting Lake and its seven inlet/outlet rivers (the three inlets of the Yangtze River and four tributaries) over the last century using stable isotope tracing and quantified the influences of climate change and human activities on OCsed. Results indicated that exogenous OC dominated the OCsed in the lake (58.2 %-89.0 %) and was lower in the west than in the east due to the differences in the material inputs and depositional conditions within the lake. Temporally, the distribution patterns of OCsed sources mainly responded to human activities in the basin rather than to climate change. Before 2005, the Yangtze River contributed the most OCsed (53.5 %-74.6 %), attributed to the high-intensity land use changes (path coefficient (r∂): 0.48, p-value < 0.01) and agriculture-industry activities (r∂: 0.44, p-value < 0.001) in the Yangtze River basin that increased soil erosion. After 2005, a large amount of Yangtze River OC was intercepted by the Three Gorges Dam, altering the OC exchange in the river-lake system and shifting OCsed dominance to the four tributaries (52.2 %-63.8 %). These findings highlight the active response of OCsed to the river-lake interaction evolution and anthropogenic control, providing critical information for regulating watershed management behavior under global change.

Constructing a cancer stem cell related prognostic model for predicting immune landscape and drug sensitivity in colorectal cancer.

Background: Colorectal cancer (CRC) ranks the second malignancy with high incidence and mortality worldwide. Cancer stem cells (CSCs) function critically in cancer progression and metastasis via the interplay with immune cells in tumor microenvironment. This study aimed to identify important CSC marker genes and parsed the role of these marker genes in CRC. Materials and methods: CRC samples' single-cell RNA sequencing data and bulk transcriptome data were utilized. Seurat R package annotated CSCs and identified CSC marker genes. Consensus clustering subtyped CRC samples based on CSC marker genes. Immune microenvironment, pathway and oxidative stress analysis was performed using ESTIMATE, MCP-counter analysis and ssGSEA analysis. A prognostic model was established by Lasso and stepAIC. Sensitivity to chemotherapeutic drugs was determined by the biochemical half maximal inhibitory concentration with pRRophetic R package. Results: We identified a total of 29 CSC marker genes related to disease-specific survival (DSS). Two clusters (CSC1 and CSC2) were determined, and CSC2 showed shorter DSS, a larger proportion of late-stage samples, and higher oxidative stress response. Two clusters exhibited differential activation of biological pathways associated with immune response and oncogenic signaling. Drug sensitivity analysis showed that 44 chemotherapy drugs were more sensitive to CSC2 that those in CSC1. We constructed a seven-gene prognostic model (DRD4, DPP7, UCN, INHBA, SFTA2, SYNPO2, and NXPH4) that was effectively to distinguish high-risk and low-risk patients. 14 chemotherapy drugs were more sensitive to high-risk group and 13 chemotherapy drugs were more sensitive to low-risk group. Combination of higher oxidative stress and risk score indicated dismal prognosis. Conclusion: The CSC marker genes we identified may help to further decipher the role of CSCs in CRC development and progression. The seven-gene prognostic model could serve as an indicator for predicting the response to immunotherapy and chemotherapy as well as prognosis of CRC patients.

Sediment organic carbon dynamics response to land use change in diverse watershed anthropogenic activities.

Sediment organic carbon (SOC) is a precious archive that synthesizes anthropogenic processes that remove geochemical fluxes from watersheds. However, the scarcity of inspection about the dynamic mechanisms of anthropogenic activities on SOC limits understanding into how key human factors drive carbon dynamics. Here, four typical basins with similar natural but significantly diverse human contexts (high-moderate-low disturbance: XJ-ZS and YJ-LS) were selected to reconstruct sedimentation rates (SR) and SOC dynamics nearly a century based on 200-cm corers. A partial least squares path model (PLS-PM) was used to establish successive (70 years) and multiple anthropogenic data (population, agriculture, land use, etc.) quantification methods for SOC. Intensified anthropogenic disturbances shifted all SR from pre-stable to post-1960s fluctuating increases (total coefficient: high: 0.63 < low: 0.47 < medium: 0.45). Although land use change was co-critical driver of SOC variations, their trend and extent differed under the dams and other disturbances (SOC mutated in high-moderate but stable in low). For high basin, land use changes increased (0.12) but dams reduced (-0.10) the downstream SOC. Furthermore, SOC mutation corresponded to soil erosion due to urbanization in both periods A and B. For moderate, SOC was reversed with the increase in afforestation and cropland (-0.19) due to the forest excitation effect and deep ploughing, which corresponded to the drought in phase B and the anthropogenic ecological project in A. For low, the increase in SOC corresponded to the Great Leap Forward deforestation in period B and the reed sweep in A, which suggested the minor land change substantially affected (0.16) SOC in fragile environments. Overall, SOC dynamics revealed that anthropogenic activities affected terrestrial and aquatic ecosystems for near the centenary, especially land use. This is constructive for agroforestry management and reservoir construction, consistent with expectations like upstream carbon sequestration and downstream carbon stabilization.

Anthropogenic activities control the source dynamics of sediment organic carbon in the lower reach of an inland river.

Sediment organic carbon (SeOC) sources with rich information can be used as a "historical archive" reflecting anthropogenic activities in the catchment, which is crucial to carbon management in the watershed. Anthropogenic activities and hydrodynamic conditions significantly influence the river environment and are reflected by the SeOC sources. However, the key drivers of the SeOC source dynamics are ambiguous, which restricts the behavior of regulating the carbon output of the basin. In this study, sediment cores from the lower reach of an inland river were selected to quantify the SeOC sources based on a centennial scale. A partial least squares path model was used to establish the relationship between anthropogenic activities and hydrological conditions with the SeOC sources. Findings showed that the exogenous advantage of SeOC composition was gradually significant (early period: 54.3%; middle period: 81%; later period: 82%) from the bottom layer to the surface layer of the sediments in the lower reach of the Xiangjiang River. Factors related to anthropogenic activities controlled the external input of SeOC (δ13C: r∂ = -0.94, P < 0.001; δ15N: r∂ = -0.66, P < 0.001). Different anthropogenic activities performed different effects. Land use change aggravated soil erosion and brought more terrestrial organic carbon to the downstream. The variation of grassland carbon input was the most obvious (from 33.6% to 18.4%). In contrast, the reservoir construction intercepted upstream sediments, which might have been the main reason for the slow growth of terrestrial organic carbon input in the downstream in the later period. This study provides a specific grafting for the SeOC records - source changes - anthropogenic activities in the lower reach of the river, which provides scientific basis for watershed carbon management.

Anthropogenic-driven chronological increase of sediment organic carbon burial in a river-lake system.

Total organic carbon (TOC) in lake sediments from upstream catchments is deposited and buried in substrate, recording historical environmental changes. However, the linkage among natural variability, anthropogenic activity, and TOC burial for has not yet been clarified. This study examined the lake sediments of five 200-cm-deep dated depositional cores in west Dongting lake, China to quantify the magnitude, allocation, and amplitude of TOC burial. 44.47-59.36% of TOC burial flux was buried at 100-200 cm, suggesting lake sediments at deep layers stored considerable carbon. TOC burial rate (BRTOC) decreased along the lake entrance to its body, which was explained by the geochemical differences. Since 1900, BRTOC presented an increasing with a 4-7 times uptrend, showing three sedimentary stages with the increased human disturbance, such as deforestation, hydroelectric facilities. Moreover, the coefficient of variation of BRTOC in the third stage was lower than that in the second stage for the implementation of watershed reforestation and reservoir construction. Our findings stressed that natural variations of lake sedimentation background induced the change of TOC burial among the depositional sites, and enhanced that anthropogenic perturbation drove its chronological increases. This research unveiled the linkage between TOC burial, natural variability, and human disturbance from the perspective of burial evolutions in a lacustrine sedimentary environment.

Multifunctional mesoporous silica-cerium oxide nanozymes facilitate miR129 delivery for high-quality healing of radiation-induced skin injury.

Radiation-induced skin injury (RISI) is an important challenge for clinical treatments. The main causes of RISI include hypoxia in the wound microenvironment, reactive oxygen species (ROS) activation, and downregulation of DNA repair proteins. Here, a multiple radioresistance strategy was designed for microRNA therapy and attenuating hypoxia. A novel mesoporous silica (MS) firmly anchored and dispersed cerium (IV) oxide (CeO2) nanoparticles to form MS-CeO2 nanocomposites, which exhibit superior activity in inhibiting radiation-induced ROS and HIF-1α activation and ultimately promote RISI wound healing. The miR129 serum concentrations in patients can promote radioresistance by directly targeting RAD17 and regulating the Chk2 pathway. Subsequently, MS-CeO2 nanocomposites with miR129 were conjugated with iRGD-grafted polyoxyethylene glycol (short for nano-miR129), which increased the stability and antibacterial character, efficiently delivered miR129 to wound blood capillaries, and exhibited low toxicity. Notably, nano-miR129 promoted radioresistance and enhanced anti-ROS therapeutic efficacy in a subcutaneous RISI mouse model. Overall, this MS-CeO2 nanozyme and miR129-based multiresistance radiotherapy protection strategy provided a promising therapeutic approach for RISI.

The application and potential non-conservatism of stable isotopes in organic matter source tracing.

Organic matter (OM) tracing is critical for understanding the processes of soil redistribution and global carbon cycling. It effectively supports ecological management and global climate change prediction. Stable isotopes are generally more source-specific compared with other tracers and identify OM sources with a higher level of accuracy. Nevertheless, stable isotopes may be enriched or depleted by physical and biochemical processes such as selective migration of particles and OM mineralization in transport and sedimentary environments, making it difficult to establish links between the source and sink regions. Literature on OM source identification tends to assume a direct link between stable isotope sources and sinks, ignoring the non-conservatism of stable isotopes. There is further literature on understanding and modeling the processes that link the sources to sinks in terms of the non-conservatism of stable isotopes. The disagreement in response to the non-conservatism lies in the lack of comprehensive understanding of stable isotope fingerprinting systems and non-conservatism. The development of stable isotope fingerprinting technology is full of challenges. This review outlines the applicability of stable isotope tracers, identification mechanisms, and associated quantitative models, intending to improve the stable isotope fingerprinting system. We highlight the non-conservatism of stable isotopes in space and time caused by physical and biochemical processes. Additionally, a decision tree is established to determine the quantitative tools, evaluation indicators, and procedures related to non-conservatism. This decision tree clarifies the process from non-conservatism detection to threshold determination of statistical quantification, which can guide the end-users to better apply stable isotope to trace OM sources.

Durable Complete Response to Pembrolizumab in Esophageal Squamous Cell Carcinoma With Divergent Microsatellite Status: A Case Report.

Microsatellite instability-high (MSI-H) is widely believed to be a biomarker for immune checkpoint inhibitors (ICIs) such as pembrolizumab in solid tumors. However, due to the low prevalence of MSI-H in most cancers, it tends to be insufficient to identify whether patients should receive ICIs according to this biomarker alone. Here, we report a Chinese esophageal squamous cell carcinoma (ESCC) patient with unusual divergent MSI status between the primary lesion (MSS) and metastatic lesion (MSI-H) which developed after platinum-based therapy and radiotherapy. Both his primary and metastatic tumors responded well to pembrolizumab-containing therapies or pembrolizumab monotherapy and maintained a complete response for over 24 months. Whole-exome sequencing and multiplex immunohistochemistry were used to examine his tissue specimens. Notably, there were multiple high-frequency mutations of DDR (DNA damage repair) genes shared in the primary lesion and metastatic lesion, especially in the latter. Besides, we observed considerable degrees of infiltrating CD3+/CD8+ lymphocytes in both of his primary tumor and metastatic tumor without obvious difference, suggesting that the conversion of microsatellite status had little effect on the infiltration of lymphocytes. Collectively, given the predictive role of DDR alterations for ICIs in other malignancies, the alterations of DDR genes might also be promising biomarkers in ESCC individuals receiving ICIs.

Chronological records of sediment organic carbon at an entrance of Dongting Lake: Response to historical meteorological events.

Lake sediments are the products of soil erosion and are strongly influenced by climate variability, particularly extreme meteorological events. Sediment organic carbon (SOC) can reflect environmental changes that affect sediment transport. However, the response of SOC chronological records to major meteorological events is relatively unknown. This study explored the chronological regularity of SOC and verified its variations using major historical meteorological events. Based on three sediment profiles with a depth of 230 cm at the Yuan River entrance to the West Dongting Lake (Hanshou entrance), the SOC chronology was reconstructed by employing the sedimentation rates calculated by 137Cs and 210Pb. The sedimentary environment then was interpreted via comparisons and quantitative analysis. The grain distribution and the S-shaped distribution of SOC reflected the general deposition regularity of organic carbon in lake sediments, which gradually stabilized with depth. The average sedimentation rates based on 137Cs and 210Pb were 1.310 and 1.319 cm a-1, respectively. Accordingly, SOC records covered the past 76 years via dating (0-100 cm), during which the SOC content first increased and subsequently stabilized. By comparing the data with the occurrence of 11 major historical meteorological events, we found that SOC generally increased after these events. Moreover, the frequent occurrence of meteorological events stabilized the SOC content. Severe floods had a greater impact on SOC content than severe droughts, causing SOC to change by up to 20.24% and 8.77%, respectively. Our findings suggest that major historical meteorological events can verify SOC chronological records, thereby highlighting their significant impacts on organic carbon variations in sediments.

Characteristics of microbial community composition and its relationship with carbon, nitrogen and sulfur in sediments.

Microorganisms play an important role in the biogeochemical cycles of lacustrine sediments. However, little is known about their vertical responses to sedimentary depths and their contributions to important element cycles such as carbon, nitrogen and sulfur. Here, we investigated the community features of sedimental prokaryotes along with vertical profiles (i.e., sedimental depths of 0-230 cm) in the Dongting watershed. In the entire profile, the bacterial diversity wavelike decreased with increasing sediment depths, whereas archaeal diversity increased monotonically in the deep layer (100-230 cm). Bacteria were more sensitive to sedimental depths than archaea (B: P < 0.001, R = 0.534; A: P < 0.001, R = 0.327). The relative abundance of the primary phylum of bacteria (e.g. Proteobacteria) and archaea (e.g. Thaumarchaeota) changed significantly with sediment layers (P < 0.05). The vertical distribution of prokaryotes in sediments was related to the changes in sediment properties (P < 0.05, e.g., the content of nutrients, pH, texture, etc.). The co-occurrence network analysis further indicated that the superficial (0-40 cm) and deep (100-230 cm) networks contained more tightly connected node groups (more modules number), while the tighter connections (shorter APL) and more complex networks (higher avgK) were seen in sub-deep (40-100 cm) sediments. Based on the FAPROTAX database, we found that the predicted prokaryotic microbial functional groups involved in the N cycle had the highest abundance (87.47%), followed by the C cycle (9.48%) and the S cycle (2.39%). In addition, these groups were enriched in the superficial and deep layers. Taken together, these results reveal a new perspective on the vertical spatial variation in microorganisms at the fine-scale of the lake sediments. Distinct microbiome response patterns may have important implications for carbon, nitrogen and sulfur cycling along with the sediment profile in Dongting lake ecosystems.