Search

Colorectal cancer (CRC) ranks third in global incidence and second in mortality. However, a comprehensive predictive model for CRC prognosis, immunotherapy response, and drug sensitivity is still lacking. Various types of programmed cell death (PCD) are crucial for cancer occurrence, progression, and treatment, indicating their potential as valuable predictors. Fourteen PCD genes were collected and subjected to dimensionality reduction using regression methods to identify key hub genes. Predictive models were constructed and validated based on bulk transcriptomes and single-cell transcriptomes. Furthermore, the tumor microenvironment, immunotherapy response, and drug sensitivity profiles among patients with CRC were explored and stratified by risk. A risk score incorporating the PCD genes FABP4, AQP8, and NAT1 was developed and validated across four independent datasets. Patients with CRC who had a high-risk score exhibited a poorer prognosis. Unsupervised clustering algorithms were used to identify two molecular subtypes of CRC with distinct features. The risk score was combined with the clinical features to create a nomogram model with superior predictive performance. Additionally, patients with high-risk scores exhibited decreased immune cell infiltration, higher stromal scores, and reduced responsiveness to immunotherapy and first-line clinical drugs compared with low-risk patients. Furthermore, the top ten non-clinical first-line drugs for treating CRC were selected based on their predicted IC50 values. Our results indicate the efficacy of the model and its potential value in predicting prognosis, response to immunotherapy, and sensitivity to different drugs in patients with CRC. [ABSTRACT FROM AUTHOR]

Global change factors, such as variation in precipitation regimes and nitrogen (N) deposition, are likely to occur simultaneously and may have profound impacts on the relative abundance of grasses differing in functional traits, such as C3 and C4 species. We conducted an extreme drought and re-watering experiment to understand differences in the resistance and recovery abilities of C3 and C4 grasses under different N deposition scenarios. A C3 perennial grass (Leymus chinensis) and two C4 grasses (annual species Chloris virgata and perennial species Hemarthria altissima) that co-occur in Northeast China were selected as experimental plants. For both C3 and C4 grasses, N addition caused a strong increase in biomass and resulted in more severe drought stress, leading to a change in the dominant photosynthetic limitation during the drought periods. Although N addition increased antioxidant enzyme activities and protective solute concentrations, the carbon fixing capacity did not fully recover to pre-drought levels by the end of the re-watering period. N addition resulted in lower resilience under the drought conditions and lower resistance at the end of the re-watering. However, N addition led to faster recovery of photosynthesis, especially in the C3 grass, which indicate that the effect of N addition on photosynthesis during drought was asymmetric, especially in the plants with different photosynthetic nitrogen use efficiency (PNUE). These findings demonstrated that nitrogen deposition may significant alter the susceptibility of C3 and C4 grass species to drought stress and re-watering, highlighting the asymmetry between resistance and resilience and to improve our understanding about plant responses to climate change.

Global change factors, such as variation in precipitation regimes and nitrogen (N) deposition, are likely to occur simultaneously and may have profound impacts on the relative abundance of grasses differing in functional traits, such as C3 and C4 species. We conducted an extreme drought and re-watering experiment to understand differences in the resistance and recovery abilities of C3 and C4 grasses under different N deposition scenarios. A C3 perennial grass (Leymus chinensis) and two C4 grasses (annual species Chloris virgata and perennial species Hemarthria altissima) that co-occur in Northeast China were selected as experimental plants. For both C3 and C4 grasses, N addition caused a strong increase in biomass and resulted in more severe drought stress, leading to a change in the dominant photosynthetic limitation during the drought periods. Although N addition increased antioxidant enzyme activities and protective solute concentrations, the carbon fixing capacity did not fully recover to pre-drought levels by the end of the re-watering period. N addition resulted in lower resilience under the drought conditions and lower resistance at the end of the re-watering. However, N addition led to faster recovery of photosynthesis, especially in the C3 grass, which indicate that the effect of N addition on photosynthesis during drought was asymmetric, especially in the plants with different photosynthetic nitrogen use efficiency (PNUE). These findings demonstrated that nitrogen deposition may significant alter the susceptibility of C3 and C4 grass species to drought stress and re-watering, highlighting the asymmetry between resistance and resilience and to improve our understanding about plant responses to climate change. [ABSTRACT FROM AUTHOR]

Backgrounds: Periprocedural myocardial injury (PMI) after elective percutaneous coronary intervention (PCI) significantly influences the prognosis of coronary artery disease (CAD). However, it was unclear whether the occurrence of PMI was associated with a series of controllable factors, such as PCI strategy or severity of CAD.Methods: A total of 544 consecutive stable CAD patients underwent elective PCI were enrolled. The main outcome is PMI, defined as troponin T after PCI was at least one value above the 99th percentile upper reference limit. Major adverse cardiac events (MACE), including all-cause death, repeat myocardial infarction and target vessel revascularization were record in the period of follow-up. Univariate and multivariate analysis was applied to assess predictors for the occurrence of PMI.Results: The incidence of PMI was 38.8% in the study. Compared with non-PMI patients (n = 333), PMI patients (n = 211) had more diseased vessels, higher Gensini and Syntax score. Meanwhile, there were higher incidence of MACE in PMI groups (9.5% vs. 3.2%, P < 0.01). We found that PMI patients underwent higher proportion of multi-vessel PCI simultaneously (32.2% vs. 10.5%, P < 0.01) and had more stents implanted (1.8 ± 0.8 vs. 1.4 ± 0.6, P < 0.01). Importantly, after simultaneously adjusted by other factors (such as age, diabetes, total cholesterol, number of diseased vessels, Gensini score and stent length), the risk of PMI was still increased 84% by multi-vessel PCI independently (OR = 1.654, 95% CI = 1.004-2.720, P < 0.05).Conclusions: The phenomenon of PMI occurred more commonly in stable CAD patients underwent multi-vessel PCI. Multi-vessel international therapy could increase the risk of PMI in elective PCI. [ABSTRACT FROM AUTHOR]

Variations in the carbon isotope signature of leaf dark-respired CO2 (δ13CR) within a single night is a widely observed phenomenon. However, it is unclear whether there are plant functional type differences with regard to the amplitude of the nighttime variation in δ13CR. These differences, if present, would be important for interpreting the short-term variations in the stable carbon signature of ecosystem respiration and the partitioning of carbon fluxes. To assess the plant functional type differences relating to the magnitude of the nighttime variation in δ13CR and the respiratory apparent fractionation, we measured the δ13CR, the leaf gas exchange, and the δ13C of the respiratory substrates of 22 species present in the agricultural-pastoral zone of the Songnen Plain, northeast China. The species studied were grouped into C3 and C4 plants, trees, grasses, and herbs. A significant nocturnal shift in δ13CR was detected in 20 of the studied species, with the magnitude of the shift ranging from 1‰ to 5.8‰. The magnitude of the nighttime variation in δ13CR was strongly correlated with the daytime cumulative carbon assimilation, which suggests that variation in δ13CR were influenced, to some extent, by changes in the contribution of malate decarboxylation to total respiratory CO2 flux. There were no differences in the magnitude of the nighttime variation in δ13CR between the C3 and C4 plants, as well as among the woody plants, herbs and graminoids. Leaf respired CO2 was enriched in 13C compared to biomass, soluble carbohydrates and lipids; however the magnitude of enrichment differed between 8 pm and 4 am, which were mainly caused by the changes in δ13CR. We also detected the plant functional type differences in respiratory apparent fractionation relative to biomass at 4 am, which suggests that caution should be exercised when using the δ13C of bulk leaf material as a proxy for the δ13C of leaf-respired CO2. [ABSTRACT FROM AUTHOR]

Objective: Given the crucial role of mitochondria in the prognosis and treatment of hepatocellular carcinoma (HCC), we aim to develop two independent mitochondrial scoring systems to separately predict patient prognosis and the likelihood of transarterial chemoembolization non-response (TACE NR). Methods: Mitochondria-related candidate genes were selected and analyzed using univariate Cox and LASSO Cox regression analyses to create a risk prognosis score (RPS). Univariate and LASSO logistic regression analyses were used to establish the risk diagnosis score (RDS). Alternative therapies for patients with TACE NR were explored using TIDE and oncoPredict algorithms. The Seurat package was used to study the involvement of the RDS genes in HCC differentiation. Results: The RPS accurately predicts the 1-5 year survival rates of patients with HCC, where higher RPS values were associated with poorer survival outcomes. The RDS model demonstrated a commendable performance in diagnosing TACE NR, as patients with a higher RDS exhibited a greater likelihood of TACE NR. RDS was associated with the infiltration of various immune cells, and patients with lower RDS tended to have higher response rates to immunotherapy and increased sensitivity to JAK1, rapamycin, and AZD2014. By contrast, patients with higher RDS values and a higher probability of TACE NR had more responsive to paclitaxel, dasatinib, and vincristine, suggesting that these drugs are potential alternative therapies. Single-cell sequencing studies have identified ACSM2A as a key player in HCC differentiation and a potential target for therapeutic intervention. Conclusion: The RPS and RDS are important reference points for predicting outcomes and guiding treatment decisions in patients with HCC. Additionally, ACSM2A shows promise as a potential therapeutic target for HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Resources in water-limited ecosystems are highly variable and unpredictable, and the maintenance of functional diversity among coexisting species is a crucial ecological strategy through which plants mitigate environmental stress. The comparison of differential eco-physiological responses among co-occurring plants in harsh environments could help provide deep insights into the coexistence mechanisms of competing species. Two coexisting desert shrubs with different photosynthetic pathways ( Haloxylon ammodendron and Tamarix ramosissima ) were selected in the Gurbantunggut Desert located in northwest China. This study detected variations in the water sources, photosynthetic parameters, stem water status, and non-structural carbohydrates of the two shrubs at three sites with different groundwater table depths during the growing seasons of 2015 and 2016 to identify distinct eco-physiological performances in coexisting plants with different functional types under fluctuating water conditions. The water sources of H. ammodendron shifted from soil water to groundwater, while T. ramosissima extracted water mainly from deep soil layers at both sites. Significant reductions in carbon assimilation and stomatal conductance in H. ammodendron with deeper groundwater table depth were detected during most drought periods, but no significant decreases in transpiration rate were detected with declining groundwater table depth. For T. ramosissima , all of these gas exchange parameters decreased with the progression of summer drought, and their relative reduction rates were larger compared with those of H. ammodendron . The stem water status of H. ammodendron deteriorated, and the relative reduction rates of water potential increased with deeper groundwater, whereas those of T. ramosissima did not differ with greater groundwater depth. These findings indicated that prolonged drought would intensify the impact of declining groundwater depth on the eco-physiology of both shrubs, but the extent to which the shrubs would respond differed. The two shrubs were segregated along the water-carbon balance continuum: the C 3 shrub T. ramosissima maximized its carbon fixation at an enormous cost of water, while greater carbon fixation was achieved with far greater water economy for H. ammodendron . These results demonstrated that the two shrubs prioritized carbon gain and water loss differently when faced with limited water sources. These mechanisms might mitigate competitive stress and enable their coexistence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tiemuerbieke, Ma and Sun.)

Global change factors, such as variation in precipitation regimes and nitrogen (N) deposition, are likely to occur simultaneously and may have profound impacts on the relative abundance of grasses differing in functional traits, such as C 3 and C 4 species. We conducted an extreme drought and re-watering experiment to understand differences in the resistance and recovery abilities of C 3 and C 4 grasses under different N deposition scenarios. A C 3 perennial grass ( Leymus chinensis ) and two C 4 grasses (annual species Chloris virgata and perennial species Hemarthria altissima ) that co-occur in Northeast China were selected as experimental plants. For both C 3 and C 4 grasses, N addition caused a strong increase in biomass and resulted in more severe drought stress, leading to a change in the dominant photosynthetic limitation during the drought periods. Although N addition increased antioxidant enzyme activities and protective solute concentrations, the carbon fixing capacity did not fully recover to pre-drought levels by the end of the re-watering period. N addition resulted in lower resilience under the drought conditions and lower resistance at the end of the re-watering. However, N addition led to faster recovery of photosynthesis, especially in the C 3 grass, which indicate that the effect of N addition on photosynthesis during drought was asymmetric, especially in the plants with different photosynthetic nitrogen use efficiency (PNUE). These findings demonstrated that nitrogen deposition may significant alter the susceptibility of C 3 and C 4 grass species to drought stress and re-watering, highlighting the asymmetry between resistance and resilience and to improve our understanding about plant responses to climate change.

Whether photosynthetic pathway differences exist in the amplitude of nighttime variations in the carbon isotope composition of leaf dark-respired CO 2 (δ 13 C l ) and respiratory apparent isotope fractionation relative to biomass (Δ R,biomass ) in response to drought stress is unclear. These differences, if present, would be important for the partitioning of C 3 -C 4 mixed ecosystem C fluxes. We measured δ 13 C l , the δ 13 C of biomass and of potential respiratory substrates and leaf gas exchange in one C 3 ( Leymus chinensis ) and two C 4 ( Chloris virgata and Hemarthria altissima ) grasses during a manipulated drought period. For all studied grasses, δ 13 C l decreased from 21:00 to 03:00 h. The magnitude of the nighttime shift in δ 13 C l decreased with increasing drought stress. The δ 13 C l values were correlated with the δ 13 C of respiratory substrates, whereas the magnitude of the nighttime shift in δ 13 C l strongly depended on the daytime carbon assimilation rate and the range of nighttime variations in the respiratory substrate content. The Δ R,biomass in the C 3 and C 4 grasses varied in opposite directions with the intensification of the drought stress. The contribution of C 4 plant-associated carbon flux is likely to be overestimated if carbon isotope signatures are used for the partitioning of ecosystem carbon exchange and the δ 13 C of biomass is used as a substitute for leaf dark-respired CO 2 . The detected drought sensitivities in δ 13 C l and differences in respiratory apparent isotope fractionation between C 3 and C 4 grasses have marked implications for isotope partitioning studies at the ecosystem level.

Unequal absorption of photons between photosystems I and II, and between bundle-sheath and mesophyll cells, are likely to affect the efficiency of the CO2-concentrating mechanism in C4 plants. Under steady-state conditions, it is expected that the biochemical distribution of energy (ATP and NADPH) and photosynthetic metabolite concentrations will adjust to maintain the efficiency of C4 photosynthesis through the coordination of the C3 (Calvin-Benson-Bassham) and C4 (CO2 pump) cycles. However, under transient conditions, changes in light quality will likely alter the coordination of the C3 and C4 cycles, influencing rates of CO2 assimilation and decreasing the efficiency of the CO2-concentrating mechanism. To test these hypotheses, we measured leaf gas exchange, leaf discrimination, chlorophyll fluorescence, electrochromatic shift, photosynthetic metabolite pools, and chloroplast movement in maize (Zea mays) and Miscanthus × giganteus following transitional changes in light quality. In both species, the rate of net CO2 assimilation responded quickly to changes in light treatments, with lower rates of net CO2 assimilation under blue light compared with red, green, and blue light, red light, and green light. Under steady state, the efficiency of CO2-concentrating mechanisms was similar; however, transient changes affected the coordination of C3 and C4 cycles in M. giganteus but to a lesser extent in maize. The species differences in the ability to coordinate the activities of C3 and C4 cycles appear to be related to differences in the response of cyclic electron flux around photosystem I and potentially chloroplast rearrangement in response to changes in light quality.