Divergent trajectories of future global gross primary productivity and evapotranspiration of terrestrial vegetation in Shared Socioeconomic Pathways.

Understanding the future trends of carbon and water fluxes between terrestrial ecosystems and the atmosphere is crucial for predicting Earth's climate dynamics. This study employs an advanced numerical approach to project global gross primary productivity (GPP) and evapotranspiration (ET) from 2001 to 2100 under various climate scenarios based on Shared Socioeconomic Pathways (SSPs). To improve predictions of vegetation dynamics, we introduce a novel model (CoLM-PVPM), an enhancement of the Common Land Model version 2014 (CoLM2014), incorporating a prognostic vegetation phenology model (PVPM). Compared to CoLM2014 that relies on satellite-based leaf area index (LAI) inputs, CoLM-PVPM predicts LAI time series using climate variables. Model validation using historical data from 2001 to 2010 demonstrates PVPM in capturing spatiotemporal variations in satellite LAI. Our modeling results indicate that annual averaged LAI and total GPP increase under SSP1-2.6 but decrease under SSP2-4.5, SSP3-7.0, and SSP5-8.5 by 2100. By comparison, annual total ET consistently increases under all SSP scenarios by 2100. Global annual averaged LAI is highly correlated with annual total GPP in all scenarios, while its correlation with annual total ET weakens in SSP2-4.5, SSP3-7.0, and SSP5-8.5. Global annual total vapor pressure deficit (VPD) and precipitation are highly correlated with annual total ET in all scenarios. As emission levels increase, the negative correlation between annual total VPD and GPP strengthens, while the correlation between annual total precipitation and GPP weakens. This research presents an improved model for predicting terrestrial vegetation processes and underscores the importance of low carbon emission scenarios in maintaining carbon-water balances in specific regions.

Water-energy-vegetation nexus explain global geographical variation in surface urban heat island intensity.

Surface urban heat island (SUHI) is a key climate risk associated with urbanization. Previous case studies have suggested that precipitation (water), radiation (energy), and vegetation have important effects on urban warming, but there is a lack of research that combines these factors to explain the global geographic variation in SUHI intensity (SUHII). Here, we utilize remotely sensed and gridded datasets to propose a new water-energy-vegetation nexus concept that explains the global geographic variation of SUHII across four climate zones and seven major regions. We found that SUHII and its frequency increase from arid zones (0.36 ± 0.15 °C) to humid zones (2.28 ± 0.10 °C), but become weaker in the extreme humid zones (2.18 ± 0.15 °C). We revealed that from semi-arid/humid to humid zones, high precipitation is often coupled with high incoming solar radiation. The increased solar radiation can directly enhance the energy in the area, leading to higher SUHII and its frequency. Although solar radiation is high in arid zones (mainly in West, Central, and South Asia), water limitation leads to sparse natural vegetation, suppressing the cooling effect in rural areas and resulting in lower SUHII. In extreme humid regions (mainly in tropical areas), incoming solar radiation tends to flatten out, which, coupled with increased vegetation as hydrothermal conditions become more favorable, leads to more latent heat and reduces the intensity of SUHI. Overall, this study offers empirical evidence that the water-energy-vegetation nexus highly explains the global geographic variation of SUHII. The results can be used by urban planners seeking optimal SUHI mitigation strategies and for climate change modeling work.

Thymidine kinase 1 drives hepatocellular carcinoma in enzyme-dependent and -independent manners.

Metabolic reprogramming plays a crucial role in the development of hepatocellular carcinoma (HCC). However, the key drivers of metabolic reprogramming underlying HCC progression remain unclear. Using a large-scale transcriptomic database and survival correlation screening, we identify thymidine kinase 1 (TK1) as a key driver. The progression of HCC is robustly mitigated by TK1 knockdown and significantly aggravated by its overexpression. Furthermore, TK1 promotes the oncogenic phenotypes of HCC not only through its enzymatic activity and production of deoxythymidine monophosphate (dTMP) but also by promoting glycolysis via binding with protein arginine methyltransferase 1 (PRMT1). Mechanistically, TK1 directly binds PRMT1 and stabilizes it by interrupting its interactions with tripartite-motif-containing 48 (TRIM48), which inhibits its ubiquitination-mediated degradation. Subsequently, we validate the therapeutic capacity of hepatic TK1 knockdown in a chemically induced HCC mouse model. Therefore, targeting both the enzyme-dependent and -independent activity of TK1 may be therapeutically promising for HCC treatment.

PRDM1/BLIMP1 induces cancer immune evasion by modulating the USP22-SPI1-PD-L1 axis in hepatocellular carcinoma cells.

Programmed death receptor-1 (PD-1) blockade have achieved some efficacy but only in a fraction of patients with hepatocellular carcinoma (HCC). Programmed cell death 1 ligand 1 (PD-L1) binds to its receptor PD1 on T cells to dampen antigen-tumor immune responses. However, the mechanisms underlying PD-L1 regulation are not fully elucidated. Herein, we identify that tumoral Prdm1 overexpression inhibits cell growth in immune-deficient mouse models. Further, tumoral Prdm1 overexpression upregulates PD-L1 levels, dampening anti-tumor immunity in vivo, and neutralizes the anti-tumor efficacy of Prdm1 overexpression in immune-competent mouse models. Mechanistically, PRDM1 enhances USP22 transcription, thus reducing SPI1 protein degradation through deubiquitination, which enhances PD-L1 transcription. Functionally, PD-1 mAb treatment reinforces the efficacy of Prdm1-overexpressing HCC immune-competent mouse models. Collectively, we demonstrate that the PRDM1-USP22-SPI1 axis regulates PD-L1 levels, resulting in infiltrated CD8+ T cell exhaustion. Furthermore, PRDM1 overexpression combined with PD-(L)1 mAb treatment provides a therapeutic strategy for HCC treatment.

Quantification of human contribution to soil moisture-based terrestrial aridity.

Current knowledge of the spatiotemporal patterns of changes in soil moisture-based terrestrial aridity has considerable uncertainty. Using Standardized Soil Moisture Index (SSI) calculated from multi-source merged data sets, we find widespread drying in the global midlatitudes, and wetting in the northern subtropics and in spring between 45°N-65°N, during 1971-2016. Formal detection and attribution analysis shows that human forcings, especially greenhouse gases, contribute significantly to the changes in 0-10 cm SSI during August-November, and 0-100 cm during September-April. We further develop and apply an emergent constraint method on the future SSI's signal-to-noise (S/N) ratios and trends under the Shared Socioeconomic Pathway 5-8.5. The results show continued significant presence of human forcings and more rapid drying in 0-10 cm than 0-100 cm. Our findings highlight the predominant human contributions to spatiotemporally heterogenous terrestrial aridification, providing a basis for drought and flood risk management.

Unexpected response of nitrogen deposition to nitrogen oxide controls and implications for land carbon sink.

Terrestrial ecosystems in China receive the world's largest amount of reactive nitrogen (N) deposition. Recent controls on nitrogen oxides (NOx = NO + NO2) emissions in China to tackle air pollution are expected to decrease N deposition, yet the observed N deposition fluxes remain almost stagnant. Here we show that the effectiveness of NOx emission controls for reducing oxidized N (NOy = NOx + its oxidation products) deposition is unforeseen in Eastern China, with one-unit reduction in NOx emission leading to only 55‒76% reductions in NOy-N deposition, as opposed to the high effectiveness (around 100%) in both Southern China and the United States. Using an atmospheric chemical transport model, we demonstrate that this unexpected weakened response of N deposition is attributable to the enhanced atmospheric oxidizing capacity by NOx emissions reductions. The decline in N deposition could bear a penalty on terrestrial carbon sinks and should be taken into account when developing pathways for China's carbon neutrality.

MGP promotes CD8+ T cell exhaustion by activating the NF-κB pathway leading to liver metastasis of colorectal cancer.

Matrix Gla protein (MGP) was originally reported as a physiological suppressor of ectopia calcification and has also been reported to be associated with cancer. However, the relation between the biological functions of MGP and the immune response in colorectal cancer (CRC) remains unclear. Here, we investigated the regulatory role of MGP in the immune microenvironment of CRC. MGP expression in CRC samples was assessed by single-cell RNA sequencing and the Gene Expression Omnibus (GEO) database, and confirmed by quantitative real-time Polymerase Chain Reaction (qRT-PCR) and immunohistochemistry analysis of human CRC samples. The effect of MGP on proliferation and invasion of CRC cells was evaluated by in vitro assays involving MGP knockdown and overexpression. Luciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay were performed to identify transcriptional regulatory sites of the nuclear factor kappa-B (NF-κB) and programmed cell death ligand 1 (PD-L1). In vivo experiments were performed in mouse model of CRC liver metastasis established via spleen injection. The results revealed that MGP was significantly upregulated in cancer cell clusters from the primary CRC or liver metastases, compared with that in the corresponding paracancerous tissues via single-cell RNA sequencing. MGP enriched intracellular free Ca2+ levels and promoted NF-κB phosphorylation, thereby activated PD-L1 expression to promote CD8+ T cell exhaustion in CRC. The luciferase reporter assay and ChIP-qPCR assay indicated that the transcriptional regulation of NF-κB upregulated PD-L1 expression. In vivo, MGP inhibition significantly decreased the rate of CRC liver metastasis, which was further reduced after combined therapy with αPD1 (anti-PD1). In conclusions, this study revealed that MGP can facilitate CD8+ T cell exhaustion by activating the NF-κB pathway, leading to liver metastasis of CRC. The combination of MGP knockdown and αPD1 can synergistically resist liver metastasis of CRC.

m6A modification of circHPS5 and hepatocellular carcinoma progression through HMGA2 expression.

N6-methyladenosine (m6A) is capable of mediating circRNA generation in carcinoma biology. Nevertheless, the posttranscriptional systems of m6A and circRNA in hepatocellular carcinoma (HCC) development are still unclear. The present study identified a circRNA with m6A modification, circHPS5, which was increased in neoplasm HCC tissues and indicated poor patient survival. Silencing of circHPS5 inhibited epithelial-mesenchymal transition (EMT) and cancer stem-like cell (CSC) phenotypes. Notably, METTL3 could direct the formation of circHPS5, and specific m6A controlled the accumulation of circHPS5. YTHDC1 facilitated the cytoplasmic output of circHPS5 under m6A modification. In addition, we demonstrated that circHPS5 can act as a miR-370 sponge to regulate the expression of HMGA2 and further accelerate HCC cell tumorigenesis. Accordingly, the m6A modification of circHPS5 was found to modulate cytoplasmic output and increase HMGA2 expression to facilitate HCC development. The new regulatory model of "circHPS5-HMGA2" provides a new perspective for circHPS5 as an important prognostic marker and therapeutic target in HCC and provides mechanistic insight for exploring the carcinogenic mechanism of circHPS5 in HCC.

Perspectives on Immunotherapy of Metastatic Colorectal Cancer.

Colorectal cancer, especially liver metastasis, is still a challenge worldwide. Traditional treatment such as surgery, chemotherapy and radiotherapy have been difficult to be further advanced. We need to develop new treatment methods to further improve the poor prognosis of these patients. The emergence of immunotherapy has brought light to mCRC patients, especially those with dMMR. Based on several large trials, some drugs (pembrolizumab, nivolumab) have been approved by US Food and Drug Administration to treat the patients diagnosed with dMMR tumors. However, immunotherapy has reached a bottleneck for other MSS tumors, with low response rate and poor PFS and OS. Therefore, more clinical trials are underway toward mCRC patients, especially those with MSS. This review is intended to summarize the existing clinical trials to illustrate the development of immunotherapy in mCRC patients, and to provide a new thinking for the direction and experimental design of immunotherapy in the future.

Identification of a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma: A case report.

RATIONALE: Gallbladder carcinoma is a malignant biliary tract tumor which is characterized by poor prognosis. Recent advances in genomic medicine have identified a few novel germline mutations that contribute to the increased risk of gallbladder carcinoma. RAD52 is a crucial human deoxyribonucleic acid (DNA) repair gene involved in maintaining genomic stability and preventing tumor occurrence. PATIENT CONCERNS: A 57-year-old man was hospitalized for space-occupying lesions in the gallbladder. DIAGNOSIS: A diagnosis of gallbladder adenocarcinoma was made based on computed tomography, B-ultrasound, blood tests, and postoperative pathology. INTERVENTIONS: Next-generation sequencing using a 599-gene panel and Sanger sequencing were performed to validate the mutation in the proband and his family members, respectively. OUTCOMES: A novel potentially pathogenic heterozygous germline RAD52 missense mutation (c.276T > A: p.N92K) was identified in the patient. Sanger sequencing revealed that this variation was not observed in unaffected family members. LESSONS: We identified a novel heterozygous germline RAD52 missense mutation in a patient with gallbladder carcinoma. Our results added to the current body of knowledge. It also provides new insights into genetic counseling and targeted therapeutic strategies for patients with gallbladder carcinoma.

CHI3L1 alleviate acute liver injury by inhibiting Th1 cells differentiation through STAT3 signaling pathway.

BACKGROUND: Acute liver injury (ALI) is a severe liver disease. Chitinase 3-like-1 (CHI3L1), a protein belonging to the glycosyl hydrolase family 18, is involved in many diseases, such as inflammatory diseases, bacterial infections, and various malignant tumors; however, the function of CHI3L1 in ALI remains unclear. The objective of this study was to evaluate the protective functions of CHI3L1 against thioacetamide (TAA)-induced ALI in mice and explore its potential mechanisms. METHODS: Data from 20 patients with ALI and 10 healthy subjects was collected. Serum CHI3L1, serum aspartate transaminase (AST), and serum alanine aminotransferase (ALT) were measured. To establish ALI mouse models, thioacetamide was intraperitoneally injected into groups of the CHI3L1-knockout (CHI3L1-KO) and wild-type (WT) mice (80 and 150 mg/kg). Recombinant CHI3L1 protein (rCHI3L1) (5 µg/kg), IFN-γ (500 ng), and WP1033 (an inhibitor of P-STAT3, 0.2 mL) were injected before TAA treatment, after which the effects were estimated. Splenic CD4+CD62L+ naive T cells were isolated from CHI3L1-KO mice and stimulated to differentiate into regulatory T (Treg) cells, T-helper 1 (Th1) cells, T-helper 2 (Th2) cells, and T-helper 17 (Th17) cells. RESULTS: Increased serum CHI3L1 levels were seen both in healthy subjects and post-therapy patients compared with ALI patients. CHI3L1 levels were negatively correlated with serum ALT and AST levels in ALI patients. CHI3L1-KO group showed higher serum ALT and AST levels than the WT group following TAA treatment, while tail vein injection of rCHI3L1 reduced liver tissue injury and improved Treg cell differentiation in vivo. In vitro experiment showed that knockout of CHI3L1 improved IFN-γ+ Th1 cell differentiation. Furthermore, intraperitoneal administration of IFN-γ produced more severe hepatocellular necrosis compared with rCHI3L1 injection alone. Mechanism study showed that T-box expressed in T cells (T-bet), and signal transducer and activator of transcription 3 (STAT3), play a critical role in adversely mediating the effect of CHI3L1, which is consistent with the finding that treatment with WP1033 down-regulated the differentiation of the Th1 cells in vitro and reduced severity of liver injury in vivo. CONCLUSIONS: CHI3L1 reduced the production of IFN-γ and inhibited Th1 cell differentiation through the STAT3 signaling pathway, which could be a potential therapeutic strategy for treating ALI.

Urban warming advances spring phenology but reduces the response of phenology to temperature in the conterminous United States.

Urbanization has caused environmental changes, such as urban heat islands (UHIs), that affect terrestrial ecosystems. However, how and to what extent urbanization affects plant phenology remains relatively unexplored. Here, we investigated the changes in the satellite-derived start of season (SOS) and the covariation between SOS and temperature (RT ) in 85 large cities across the conterminous United States for the period 2001-2014. We found that 1) the SOS came significantly earlier (6.1 ± 6.3 d) in 74 cities and RT was significantly weaker (0.03 ± 0.07) in 43 cities when compared with their surrounding rural areas (P < 0.05); 2) the decreased magnitude in RT mainly occurred in cities in relatively cold regions with an annual mean temperature <17.3 °C (e.g., Minnesota, Michigan, and Pennsylvania); and 3) the magnitude of urban-rural difference in both SOS and RT was primarily correlated with the intensity of UHI. Simulations of two phenology models further suggested that more and faster heat accumulation contributed to the earlier SOS, while a decrease in required chilling led to a decline in RT magnitude in urban areas. These findings provide observational evidence of a reduced covariation between temperature and SOS in major US cities, implying the response of spring phenology to warming conditions in nonurban environments may decline in the warming future.

Evaluating and Improving the Performance of Three 1-D Lake Models in a Large Deep Lake of the Central Tibetan Plateau.

The ability of FLake, WRF-Lake, and CoLM-Lake models in simulating the thermal features of Lake Nam Co in Central Tibetan Plateau has been evaluated in this study. All the three models with default settings exhibited distinct errors in the simulated vertical temperature profile. Then model calibration was conducted by adjusting three (four) key parameters within FLake and CoLM-Lake (WRF-Lake) in a series of sensitive experiments. Results showed that each model's performance is sensitive to the key parameters and becomes much better when adjusting all the key parameters relative to tuning single parameter. Overall, setting the temperature of maximum water density to 1.1 °C instead of 4 °C in the three models consistently leads to improved vertical thermal structure simulation during cold seasons; reducing the light extinction coefficient in FLake results in much deeper mixed layer and warmer thermocline during warm seasons in better agreement with the observation. The vertical thermal structure can be clearly improved by decreasing the light extinction coefficient and increasing the turbulent mixing in WRF-Lake and CoLM-Lake during warm seasons. Meanwhile, the modeled water temperature profile in warm seasons can be significantly improved by further replacing the constant surface roughness lengths by a parameterized scheme in WRF-Lake. Further intercomparison indicates that among the three calibrated models, FLake (WRF-Lake) performs the best to simulate the temporal evolution and intensity of temperature in the layers shallower (deeper) than 10 m, while WRF-Lake is the best at simulating the amplitude and pattern of the temperature variability at all depths.

Observational Evidence for Desert Amplification Using Multiple Satellite Datasets.

Desert amplification identified in recent studies has large uncertainties due to data paucity over remote deserts. Here we present observational evidence using multiple satellite-derived datasets that desert amplification is a real large-scale pattern of warming mode in near surface and low-tropospheric temperatures. Trend analyses of three long-term temperature products consistently confirm that near-surface warming is generally strongest over the driest climate regions and this spatial pattern of warming maximizes near the surface, gradually decays with height, and disappears in the upper troposphere. Short-term anomaly analyses show a strong spatial and temporal coupling of changes in temperatures, water vapor and downward longwave radiation (DLR), indicating that the large increase in DLR drives primarily near surface warming and is tightly associated with increasing water vapor over deserts. Atmospheric soundings of temperature and water vapor anomalies support the results of the long-term temperature trend analysis and suggest that desert amplification is due to comparable warming and moistening effects of the troposphere. Likely, desert amplification results from the strongest water vapor feedbacks near the surface over the driest deserts, where the air is very sensitive to changes in water vapor and thus efficient in enhancing the longwave greenhouse effect in a warming climate.

Soil diversity as affected by land use in China: consequences for soil protection.

Rapid land-use change in recent decades in China and its impact on terrestrial biodiversity have been widely studied, particularly at local and regional scales. However, the effect of land-use change on the diversity of soils that support the terrestrial biological system has rarely been studied. Here, we report the first effort to assess the impact of land-use change on soil diversity for the entire nation of China. Soil diversity and land-use effects were analyzed spatially in grids and provinces. The land-use effects on different soils were uneven. Anthropogenic soils occupied approximately 12% of the total soil area, which had already replaced the original natural soils. About 7.5% of the natural soil classes in China were in danger of substantial loss, due to the disturbance of agriculture and construction. More than 80% of the endangered soils were unprotected due to the overlook of soil diversity. The protection of soil diversity should be integrated into future conservation activities.

Particle-size distribution models for the conversion of Chinese data to FAO/USDA system.

We investigated eleven particle-size distribution (PSD) models to determine the appropriate models for describing the PSDs of 16349 Chinese soil samples. These data are based on three soil texture classification schemes, including one ISSS (International Society of Soil Science) scheme with four data points and two Katschinski's schemes with five and six data points, respectively. The adjusted coefficient of determination r (2), Akaike's information criterion (AIC), and geometric mean error ratio (GMER) were used to evaluate the model performance. The soil data were converted to the USDA (United States Department of Agriculture) standard using PSD models and the fractal concept. The performance of PSD models was affected by soil texture and classification of fraction schemes. The performance of PSD models also varied with clay content of soils. The Anderson, Fredlund, modified logistic growth, Skaggs, and Weilbull models were the best.

Developed and developing world responsibilities for historical climate change and CO2 mitigation.

At the United Nations Framework Convention on Climate Change Conference in Cancun, in November 2010, the Heads of State reached an agreement on the aim of limiting the global temperature rise to 2 °C relative to preindustrial levels. They recognized that long-term future warming is primarily constrained by cumulative anthropogenic greenhouse gas emissions, that deep cuts in global emissions are required, and that action based on equity must be taken to meet this objective. However, negotiations on emission reduction among countries are increasingly fraught with difficulty, partly because of arguments about the responsibility for the ongoing temperature rise. Simulations with two earth-system models (NCAR/CESM and BNU-ESM) demonstrate that developed countries had contributed about 60-80%, developing countries about 20-40%, to the global temperature rise, upper ocean warming, and sea-ice reduction by 2005. Enacting pledges made at Cancun with continuation to 2100 leads to a reduction in global temperature rise relative to business as usual with a 1/3-2/3 (CESM 33-67%, BNU-ESM 35-65%) contribution from developed and developing countries, respectively. To prevent a temperature rise by 2 °C or more in 2100, it is necessary to fill the gap with more ambitious mitigation efforts.

Impact of vegetation removal and soil aridation on diurnal temperature range in a semiarid region: application to the Sahel.

Increased clouds and precipitation normally decrease the diurnal temperature range (DTR) and thus have commonly been offered as explanation for the trend of reduced DTR observed for many land areas over the last several decades. Observations show, however, that the DTR was reduced most in dry regions and especially in the West African Sahel during a period of unprecedented drought. Furthermore, the negative trend of DTR in the Sahel appears to have stopped and may have reversed after the rainfall began to recover. This study develops a hypothesis with climate model sensitivity studies showing that either a reduction in vegetation cover or a reduction in soil emissivity would reduce the DTR by increasing nighttime temperature through increased soil heating and reduced outgoing longwave radiation. Consistent with empirical analyses of observational data, our results suggest that vegetation removal and soil aridation would act to reduce the DTR during periods of drought and human mismanagement over semiarid regions such as the Sahel and to increase the DTR with more rainfall and better human management. Other mechanisms with similar effects on surface energy balance, such as increased nighttime downward longwave radiation due to increased greenhouse gases, aerosols, and clouds, would also be expected to have a larger impact on DTR over drier regions.