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Understanding the origins and processes of riverine dissolved inorganic carbon (DIC) is crucial for predicting the global carbon cycle with projected, more frequent climate extremes yet our knowledge has remained fragmented. Here we ask: How and how much do DIC production and export vary across space (shallow vs. deep, uphill vs. depression) and time (daily, seasonal, and annual)? How do the relative contributions of biogenic (soil respiration) and geogenic (carbonate weathering) sources differ under different temperature and hydrological conditions? We answer these questions using a catchment‐scale reactive transport model constrained by stream flow, stable water isotopes, stream DIC, and carbon isotope data from a headwater karstic catchment in southwest China in a subtropical monsoon climate. Results show climate seasonality regulates the timing of DIC production and export. In hot‐wet seasons, high temperature accelerates soil respiration and carbonate weathering (up to a factor of three) via elevating soil CO2 and carbonate solubility, whereas high discharge enhances export by two orders of magnitude compared to cold‐dry seasons. Carbonate weathering is driven more by soil CO2 than water flow. At the annual scale, 92.9% and 7.1% of DIC was produced in shallow and deep zone, respectively, whereas 64.5% and 35.5% of DIC was exported from shallow and deep zone, respectively. These results highlight the uniqueness of subtropical karst areas as synchronous reactors and transporters of DIC during the hot‐wet monsoon, contrasting the asynchronous production and export in other climate regions. A future hotter and wetter climate with more intensive storms in the region may further intensify DIC production and export, accentuating the potential of subtropical karst regions as global hot spots for carbon cycling. Plain Language Summary Understanding the origins and movement of dissolved inorganic carbon (DIC) in rivers is crucial for comprehending global carbon dynamics. Here we used a model and field data from a karstic region in southwest China to understand these processes. We found that the hot and wet seasons are important for both DIC production and export to the stream, because the warm temperature and rapid water movement speeds up the breakdown of soil carbon and rocks into DIC. In addition, the shallow soil produces more DIC compared to deeper rocks. The origins of DIC also vary with the seasons. In the hot‐wet season, it mostly comes from living things in the soil, while in the cold‐dry season, it comes more from non‐living sources like rocks. This work suggests that karst formations in hot‐wet monsoon climates might be significant in capturing CO2. In the hotter and wetter climate, even more DIC may be produced and transported into rivers and streams. Key Points Synchronous amplified production and export of dissolved inorganic carbon (DIC) in the hot‐wet season in subtropical monsoon climate Shallow and deep (vertical) contrasts are more pronounced than uphill‐depression (landscape) contrasts Riverine DIC is mostly biogenic from shallow soil respiration, especially in the hot‐wet monsoon (58%–66%)

The episodic growth of high-elevation orogenic plateaux is controlled by a series of geodynamic processes. However, determining the underlying mechanisms that drive plateau growth dynamics over geological history and constraining the depths at which growth originates, remains challenging. Here we present He-CO 2 -N 2 systematics of hydrothermal fluids that reveal the existence of a lithospheric-scale fault system in the southeastern Tibetan Plateau, whereby multi-stage plateau growth occurred in the geological past and continues to the present. He isotopes provide unambiguous evidence for the involvement of mantle-scale dynamics in lateral expansion and localized surface uplift of the Tibetan Plateau. The excellent correlation between 3 He/ 4 He values and strain rates, along the strike of Indian indentation into Asia, suggests non-uniform distribution of stresses between the plateau boundary and interior, which modulate southeastward growth of the Tibetan Plateau within the context of India-Asia convergence. Our results demonstrate that deeply-sourced volatile geochemistry can be used to constrain deep dynamic processes involved in orogenic plateau growth. Deeply-sourced volatiles are releasing from orogenic plateau regions, providing windows to plateau growth dynamics occurring at variable depths. Here the authors show that mantle-derived volatiles reveal the involvement of mantle dynamics in southeastward growth of the Tibetan Plateau.

A heavy load of nitrogenous compounds reflects nutrient loss and influences water quality in large rivers. Nitrogenous concentrations and dual isotopes of nitrate were measured to ascertain the spatial and temporal distributions of nitrate transformation in the Yellow River, the second-longest river in China. Assessment of the long-term record indicates that [NO 3 − –N] has increased by two-fold over the past three decades. Weekly observation of ammonium over a twelve-year period revealed high concentrations and suggests impairment of water quality, particularly since 2011. The estimated total dissolved nitrogen flux was 7.2 times higher in middle reaches than that at head waters. Anthropogenic nitrogen sources become more important in lower section of the upper reaches and middle reaches because of intensive agricultural activities and urban input. Nitrate in the lower reaches was mainly derived from transportation of upstream nitrate and point sources from cities. The spatial variation of ammonium and nitrate isotopes show that nitrification is a key process governing nitrogen transformation. Riverine biological processes could potentially be responsible for the shift of nitrate isotope signature. The first step to reducing nitrogen load and improving water quality will be containment and careful management of sources from urban input, sewage waste and irrigation runoff.

Riverine dissolved inorganic carbon (DIC), essential for understanding terrestrial carbon cycling, is undergoing dramatic changes due to climate change and human disturbances. Quantifying how these changes impact DIC fluxes from land to rivers has remained challenging due to limited long‐term data and complex, interacting drivers. Here we ask the question: How and to what extent do climate and land‐cover changes distinctively influence long‐term seasonal and annual trends of DIC production and export? We developed a reactive transport model, constrained by three decades of streamflow, DIC, and carbon isotope data, for a karst catchment in southwest China simultaneously experiencing a warmer, drier climate (increasing aridity) and forest recovery. Results show that from 1980 to 2010s, precipitation has declined from 1,261 to 1,005 mm/yr, and discharge from 700 to 552 mm/yr, with no significant change in evapotranspiration. DIC production and export have declined at the rates of 2.3 × 105 and 5.4 × 105 mol C/yr/yr, respectively. Drier climate and reduced discharge diminish carbonate weathering but also store more produced DIC, resulting in higher DIC concentrations over time but a twofold decline in DIC export compared to its production. Interestingly, although forest recovery elevates organic carbon content, cooling soils and lower soil moisture reduce rates of soil respiration. Scenario analysis shows that forest recovery accounts for 91% of the production decline, while increasing climate aridity explains 78% of the export reduction. Seasonal analysis further reveals that soil respiration declines most during hot‐wet seasons but calcite weathering drops more in cold‐dry seasons. These findings underscore the differential impacts of climate and land‐cover changes on carbon transport and transformation processes, which are crucial for understanding carbon cycling and budgets under evolving environmental conditions.

Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression. We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA. Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network. These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.

Novel neoadjuvant therapy regimens are warranted for oral squamous cell carcinoma (OSCC). In this phase I trial (NCT04393506), 20 patients with locally advanced resectable OSCC receive three cycles of camrelizumab (200 mg, q2w) and apatinib (250 mg, once daily) before surgery. The primary endpoints are safety and major pathological response (MPR, defined as ≤10% residual viable tumour cells). Secondary endpoints include 2-year survival rate and local recurrence rate (not reported due to inadequate follow-up). Exploratory endpoints are the relationships between PD-L1 combined positive score (CPS, defined as the number of PD-L1-stained cells divided by the total number of viable tumour cells, multiplied by 100) and other immunological and genomic biomarkers and response. Neoadjuvant treatment is well-tolerated, and the MPR rate is 40% (8/20), meeting the primary endpoint. All five patients with CPS ˃10 achieve MPR. Post-hoc analysis show 18-month locoregional recurrence and survival rates of 10.5% (95% CI: 0%–24.3%) and 95% (95% CI: 85.4%–100.0%), respectively. Patients achieving MPR show more CD4+ T-cell infiltration than those without MPR (P = 0.02), and decreased CD31 and ɑ-SMA expression levels are observed after neoadjuvant therapy. In conclusion, neoadjuvant camrelizumab and apatinib is safe and yields a promising MPR rate for OSCC. In patients with locally advanced resectable oral squamous cell carcinoma (OSCC), the risk of recurrence and metastasis following treatment is high. Here, a phase I clinical trial reports safety and pathological response of neoadjuvant camrelizumab and apatinib in patients with locally advanced resectable OSCC.

Anthropogenic perturbations have substantially altered riverine carbon cycling worldwide, exerting influences on dissolved carbon dioxide (CO2) and methane (CH4) dynamics at multiple levels. However, the magnitude and role of anthropogenic activities in modulating carbon emissions across entire river networks, as well as the influence of climatic controls, remain largely unresolved. Here, we explore the controlling factors of riverine CO2 and CH4 dynamics across 62 subtropical, monsoon‐influenced streams and rivers through basin‐wide seasonal measurements. We found that land use and aquatic metabolism played significant roles in regulating the spatial and temporal patterns of both gases. Increased nutrient levels and organic matter contributed to higher partial pressure of CO2 (pCO2) and CH4 (pCH4). Dissolved oxygen, stable carbon isotope of dissolved inorganic carbon, the proportion of impervious surface, catchment slope, and river width were the major predictors for pCO2. For pCH4, the major predictors were Chlorophyll a and water temperature, which influence organic matter availability and methanogenesis. Seasonal variations in pCO2 and pCH4 were strongly modulated by hydroclimatic conditions, with temperature markedly regulating river ecosystem metabolism. These findings highlight the likelihood of significant changes in riverine carbon emissions as climate changes and land use patterns evolve, thereby profoundly affecting the global carbon cycle. Key Points Land use and aquatic metabolism greatly regulate the riverine CO2 and CH4 dynamics Seasonal pCO2 and pCH4 variations are strongly governed by hydroclimatic conditions Urbanization and climate warming will further enhance riverine CH4 and CO2 emissions

Aldehyde dehydrogenase 2 (ALDH2) is a new therapeutic target in the central nervous system. However, the association between ALDH2 and brain edema following ischemic stroke (IS) remains unclear. The present study was investigated to whether active ALDH2 can attenuate brain edema by using a rat model of IS, with the aim of clarifying the underlying mechanisms involved. Rats were administered the ALDH2 agonist Alda-1, vehicle or the ALDH2 inhibitor cyanamide (CYA) 15 min prior to a 1.5 h middle cerebral artery occlusion (MCAO) surgery. The effects of ALDH2 were subsequently investigated 24 h after reperfusion by evaluating neurological function, infarct sizes, brain edema volumes, 4-hydroxy-2-nonenal (4-HNE) levels, and aquaporin 4 (AQP4) protein expression. The results demonstrated that increasing ALDH2 activity significantly improved neurological deficits, reduced infarct sizes, and attenuated brain edema after MCAO. Alda-1 administration led to decreased 4-HNE levels and inhibited AQP4 protein expression in the peri-infarct section of the brain. Whereas, CYA administration increased 4-HNE levels, AQP4 expression, and simultaneously aggravated brain edema following MCAO. In conclusion, increasing ALDH2 activity can improve brain edema, infarct volumes, and reduce neurological impairment in a rat IS model. The therapeutic benefits of ALDH2 are related to 4-HNE clearance and AQP4 down-regulation.