TIM3/CEACAM1 pathway involves in myeloid-derived suppressor cells induced CD8+ T cells exhaustion and bone marrow inflammatory microenvironment in myelodysplastic syndrome.

Myeloid-derived suppressor cells (MDSC) induced cellular immune deficiency and bone marrow inflammatory microenvironment play an important role in the pathogenesis and progression of myelodysplastic syndrome (MDS), but the underlying mechanism remains unclear. Here, we revealed that immune checkpoint protein TIM3 and CEACAM1 were highly demonstrated on MDSC and CD8+ T cells in MDS patients. CD8+ T cells were reduced in number and function and presented a exhaustion state. The levels of pro-inflammatory cytokines (IL-1ß, IL-18) and CEACAM1 were raised in bone marrow supernatants and MDSC culture supernatants. Blocking or neutralizing TIM3/CEACAM1 and IL-1ß/IL-18 partially reversed exhaustion of CD8+ T cells. Moreover, TIM3 correlated with NF-κB /NLRP3 inflammatory pathway. The levels of NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 were all increased in MDSC of MDS. Co-culturing MDSC from MDS patients with rhCEACAM1 enhanced NF-κB/NLRP3/Caspase-1/IL-1ß and IL-18 levels, whereas blocking TIM3 could partially reverse the above manifestations. These results indicated that TIM3/CEACAM1 pathway involved in CD8+ T cells exhaustion and might activate the NF-κB/NLRP3/Caspase-1 pathway in MDSC, increasing pro-inflammatory cytokines secretion in MDS bone marrow microenvironment. This study provided a basis for applying immune checkpoint inhibitors that could simultaneously modulate pro-inflammatory cytokine secretion and enhance anti-tumour immune function in the treatment of MDS.

The expression and clinical significance of CD59 and FLAER in Chinese adult AML patients.

BACKGROUND: The role of CD59 and fluorescently labeled aerolysin (FLAER) in acute myeloid leukemia (AML) remains unclear and requires further investigation. To explore the relationship between CD59, FLAER, and AML, we investigated CD59 and FLAER expression in AML and analyzed their relationship with clinical characteristics of AML patients. METHODS: We employed flow cytometry (FCM) to analyze CD59 and FLAER expression in 161 AML patients at Tianjin Medical University General Hospital and evaluated its association with sex, white blood cell (WBC) count, platelet (PLT) count, thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer(D-D), and lactate dehydrogenase (LDH), followed by analyzing its connection with disease progression and complete remission (CR). RESULTS: CD59 and FLAER deficiencies were identified in AML patients. Compared with CR group, non-CR group patients revealed more CD59 and FLAER deficiency. Compared with non-acute promyelocytic leukemia (M3) group, M3 group patients had more CD59 and FLAER deficiency. CD59- level in primordial cells of M3 patients was positively correlated with primordial cell ratio (r = 0.660, p = 0.003). Additionally, we discovered that the decline in CD59 and FLAER levels might be linked to higher D-D and LDH in AML patients. The difference was statistically significant (p < 0.05). CONCLUSIONS: We demonstrated that the decline in CD59 and FLAER levels was associated with leukemia cell proliferation and abnormal coagulation function in AML, suggesting that they could serve as a predictor of AML coagulation dysfunction, particularly in M3.

Various quantification methods for estimating ammonia volatilization from wheat-maize cropping system.

Ammonia volatilization (AV) dominates the pathway of nitrogen (N) fertilizer losses in crops throughout the world. However, different methods are highly responsible for the different measurements of AV. The existing techniques were separated into static chamber methods (SCM), dynamic chamber methods (DCM), calibrated Dräger-tube method (DTM) and micrometeorological methods (MMM), which were analyzed by a meta-study of 595 observations from 33 published studies. An exponential relationship (P < 0.01) was found between AV and the N fertilizer applied to wheat and maize using all the methods. The amount of AV using SCM was the lowest. The AV monitored by DCM was 24.5%-55.0% (wheat) and 46.9%-65.0% (maize) lower than that for the DTM. Additionally, the AV measured by DTM did not differ significantly in the wheat season but was 58.9% lower (P < 0.05) in the maize season than that in the MMM. To reveal the influencing factors responsible that were for DCM and DTM, a field experiment was conducted during the period of Oct. 2016 to Oct. 2017. The study indicated that the AV was 15.8%-28.3% (wheat, P < 0.05) and 36.7%-44.2% (maize, P < 0.05) lower when monitored by the DCM than when estimated by DTM. The concentration of soil NH4+-N, air temperature, and wind speed positively correlated with the NH3 fluxes. In addition, there was a significant linear correlation (P < 0.01) between the AV measured by DCM and DTM when the wind speed was <1.5 m s-1. This study highlighted the fact that wind speed was the main factor that caused the large difference between DCM and DTM. Herein, DTM or MMM was first recommended, and DCM was accepted when wind speed was <1.5 m s-1 for quantitative estimates of AV. However, only a straight comparison between DCM and DTM under the same field experiment was done, the other comparisons only being based on similar fertilization and environmental conditions. Consequently, the differences between methods have to be treated carefully.

Environmental impacts and production performances of organic agriculture in China: A monetary valuation.

Organic agriculture has developed rapidly in China since the 1990s, driven by the increasing domestic and international demand for organic products. Quantification of the environmental benefits and production performances of organic agriculture on a national scale helps to develop sustainable high yielding agricultural production systems with minimum impacts on the environment. Data of organic production for 2013 were obtained from a national survey organized by the Certification and Accreditation Administration of China. Farming performance and environmental impact indicators were screened and indicator values were defined based on an intensive literature review and were validated by national statistics. The economic (monetary) values of farming inputs, crop production and individual environmental benefits were then quantified and integrated to compare the overall performances of organic vs. conventional agriculture. In 2013, organically managed farmland accounted for approximately 0.97% of national arable land, covering 1.158 million ha. If organic crop yields were assumed to be 10%-15% lower than conventional yields, the environmental benefits of organic agriculture (i.e., a decrease in nitrate leaching, an increase in farmland biodiversity, an increase in carbon sequestration and a decrease in greenhouse gas emissions) were valued at 1921 million RMB (320.2 million USD), or 1659 RMB (276.5 USD) per ha. By reducing the farming inputs, the costs saved was 3110 million RMB (518.3 million USD), or 2686 RMB (447.7 USD) per ha. The economic loss associated with the decrease in crop yields from organic agriculture was valued at 6115 million RMB (1019.2 million USD), or 5280 RMB (880 USD) per ha. Although they were likely underestimated because of the complex relationships among farming operations, ecosystems and humans, the production costs saved and environmental benefits of organic agriculture that were quantified in our study compensated substantially for the economic losses associated with the decrease in crop production. This suggests that payment for the environmental benefits of organic agriculture should be incorporated into public policies. Most of the environmental impacts of organic farming were related to N fluxes within agroecosystems, which is a call for the better management of N fertilizer in regions or countries with low levels of N-use efficiency. Issues such as higher external inputs and lack of integration cropping with animal husbandry should be addressed during the quantification of change of conventional to organic agriculture, and the quantification of this change is challenging.

The effects of salinity on coupled nitrification and aerobic denitrification in an estuarine system.

Salinity has significant effects on nitrification and denitrification processes, particularly in estuarine systems. A dissolved oxygen-enriched river and its estuary in northern China were selected to investigate the impact of salinity gradients (0.6, 4, 7.6, 11.4 and 14.7‰) obtained from the mixing of river samples and estuarine samples with different proportions on coupled nitrification and aerobic denitrification via incubation experiments (35 and 10 °C). Results indicated that: (a) nitrification and coupled nitrification-aerobic denitrification occurred for all treatments, which resulted in NO3- being either accumulated or removed at the end of the incubation; (b) a suitable range of salinity is 4.0-11.4‰ for nitrification and 4.0-7.6‰ for coupled nitrification-aerobic denitrification; and (c) the relatively higher temperature (35 °C) can effectively stimulate N transformation processes compared to the lover temperature (10 °C) in the incubation experiment.

Decades-long organic tea production is distinguished by N deficiency: Evidence from soil and tea δ15N data.

To investigate the possibility of identifying commercial organic teas from conventional teas based on their isotopic signatures, we sampled tea leaves and soil samples from three tea gardens in Pu'er, China, that underwent decades of certified organic cultivation and compared them with adjacent conventional gardens. We found that long-term organic tea cultivation increased the soil organic carbon and soil pH but significantly decreased the total N content of tea. Higher δ15N values were observed in the organic teas, but significant overlap existed with non-organic teas. The lower N content of the organic tea and contrasting pattern between the organic tea δ15N and soil δ15N suggested that the decline of the N availability could potentially act as a robust characteristic for discriminating between organic and non-organic tea cultivation systems. Further analysis implies that combining tea and soil N content with δ15N value is a promising approach to organic tea identification.

Occurrence of organic chlorinated pesticides and their ecological effects on soil protozoa in the agricultural soils of North Western Beijing, China.

The occurrence of ∑HCHs, ∑DDTs, protozoa abundance and their community structure in surface soils of orchards, vegetable lands, and barren lands in northern west outskirts of Beijing were detected in order to investigate the protozoa responses to low dose organic chlorinated Pesticides (OCPs) after long-term field-based exposure. Significant differences in total concentrations of HCHs and DDTs were found among the three general groups ranking in decreasing order of concentration from orchard>vegetable lands >barren lands. Ciliate was the rare group in surface soils of all the sampling groups. The abundance of flagellate, ciliate, and amoebae in vegetable soils were significantly higher than those in orchard soils. The abundance of all the taxa of protozoa was strongly negative correlated with the residue level of ∑HCHs and ∑DDTs (P<0.05) in agricultural soils. However, no negative correlation between the residue levels of OCPs and protozoa abundance was shown in both the orchard and the barren soils. This field study demonstrated a considerable long-term impact of the OCPs residue on the abundance of protozoa in soils, and that the abundance of soil protozoa was much more influenced by land use type in association with different soil properties.

Upregulation of S100A6 and its relation with CD34+ cells apoptosis in high-risk myelodysplastic syndromes patients.

Objectives: Myelodysplastic syndromes (MDS) are a group of myeloid malignancies characterized by peripheral blood cytopenia and hematopoietic dysplasia that often progress to acute myeloid leukemia (AML). Increased apoptosis of normal hematopoietic cells and decreased apoptosis of malignant clonal hematopoietic cells in patients with MDS is some of the mechanisms leading to ineffective hematopoietic cells in the bone marrow. S100 calcium-binding protein A6 (S100A6) is upregulated in many malignancies. The overexpression of S100A6 in these malignancies has been associated with proliferation, migration, and invasion phenotypes in cancer cells, and we aimed to investigate the expression of S100A6 in CD34+ cells and the relationship between S100A6 expression and apoptosis of CD34+ cells in high-risk patients with MDS. Methods: We measured S100A6 mRNA expression in bone marrow (BM) CD34+ cells from high-risk patients with MDS using RT-PCR. Next, we examined S100A6 expression in CD34+ cells using flow cytometry. We also analyzed the correlation between CD34+ cell apoptosis and S100A6 expression in high-risk patients with MDS. Results: Our data showed increased S100A6 mRNA expression in CD34+ cells in patients with MDS (1.05 ± 0.69 vs. 0.17 ± 0.12; P＜0.01). The expression of S100A6 in BM CD34+ cells also increased (58.40 ± 13.18 vs. 45.83 ± 15.01). The expression of S100A6 in CD34+ cells and apoptosis of CD34+ cells were negatively correlated in patients (r = -0.75; P < 0.01). Conclusions: Collectively, S100A6 may be a potential marker of CD34+ cells in high-risk patients with MDS and may participate in the pathological behaviors of CD34+ cells, such as evasion of apoptosis. Thus, S100A6 may be a potential target for eliminating minimal residual disease.

Disentangling the impact of straw incorporation on soil microbial communities: Enhanced network complexity and ecological stochasticity.

Straw incorporation is typically employed to enhance the nutrient content of soil and promote crop growth in intensive agricultural systems. Despite studies regarding the effects of straw incorporation on soil microbial communities, the underlying mechanisms of its effect on community co-occurrence interactions and assembly processes remain poorly understood. Herein, soil samples with or without straw incorporation were collected across a latitudinal gradient from north to central China. We found that straw incorporation considerably altered the structure of soil microbial community. The relative abundance of bacterial Latescibacterota and fungal Mortierellomycota were higher in straw-amended soils owing to their ability to decompose straw residues. The co-occurrence network in straw-amended soil exhibited greater complexity, including more network connectivity and keystone species, and higher average degrees and clustering coefficients compared with the control sample network. The network robustness and vulnerability indices suggested that straw incorporation increased the microbial network stability. Normalized stochastic ratios demonstrated that the stochastic process was the dominant mechanisms shaping the assembly of microbial communities in straw-amended soils. Concurrently, null model analysis revealed that straw increased the contribution of dispersal limitation to the assembly of bacterial and fungal communities. The migration rate of the microbial community, obtained from Sloan neutral community model, was relatively low in straw-amended soil at all the sample sites, potentially indicating the great importance of dispersal limitation. These findings would enhance our understanding of the ecological patterns and interactions of soil microbial communities in response to straw incorporation.

Donor CD7 Chimeric Antigen Receptor T Cell Bridging to Allogeneic Hematopoietic Stem Cell Transplantation for T Cell Hematologic Malignancy.

It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Here we report on the efficacy and safety of donor CD7 chimeric antigen receptor (CAR) T cell therapy (CAR-T) bridging to allo-HSCT in treating 12 patients with relapsed/refractory (r/r) T-ALL or T-cell lymphoblastic lymphoma (T-LBL). The median time from CAR-T infusion to allo-HSCT was 33.5 days (range, 30 to 55 days). With reduced-intensity conditioning, all patients except 1 successfully engrafted. With a mean follow-up of 301 days (range, 238 to 351 days), the remaining 11 patients were alive and disease-free at their last follow-up. Acute graft-versus-host disease (GVHD) was observed in 3 patients, and chronic GVHD developed in 3 patients, all with a limited pattern. Under the current protocol, infection was the main complication post-transplantation, and all infections were well controlled except in 1 patient, who died of multiple organ failure caused by an infection-induced inflammatory cytokine storm at days 14 post-transplantation. One patient relapsed (CD7+), and 3 patients became minimal residual disease (MRD) positive (CD7+ in 1, CD7- in 1, fusion gene positive only in 1). Subsequently, all 3 of these patients achieved an MRD-negative complete remission with either CD7 CAR-T reinfusion or immunosuppressive agent withdrawal. Our study shows for the first time that a novel strategy of donor CD7 CAR-T bridging to allo-HSCT can be highly effective and feasible in improving disease-free survival for patients with r/r T-ALL or T-LBL.

Assessing the environmental sustainability of different soil disinfestation methods used in solar greenhouse vegetable production systems.

Overuse of fertilizers and irrigation and continuous monocropping is increasingly jeopardizing vegetable production in solar greenhouses as it causes serious soil degradation and the spread of soil-borne diseases. As a countermeasure, the practice of anaerobic soil disinfestation (ASD) has been recently introduced, which is carried out during the summer fallow period. However, ASD may increase N leaching and greenhouse gas (GHG) emissions when large amounts of chicken manure are applied. This study assesses how the use of different amounts of chicken manure (CM) combined with rice shells (RS) or maize straw (MS) affects soil O2 availability, N leaching, and GHG emissions during and following the ASD period. Application of RS or MS alone effectively stimulated long-lasting soil anaerobiosis without major stimulating effects on N2O emissions and N leaching. Seasonal N leaching and N2O emissions were in the ranges of 144-306 and 3-44 kg N ha-1, respectively, and were strongly increasing with increasing rates of manure application. Combining high rates of manure application with the additional incorporation of crop residues further increased N2O emissions by 56 %-90 % as compared to the standard practice of farmers (1200 kg N ha-1 CM). About 56 %-91 % of seasonal N2O emissions occurred during the ASD period, whereas N leaching mainly occurred in the cropping period (75 %-100 %). Our study shows, that for priming ASD incorporation of crop residue is sufficient and that the addition of chicken manure for ASD is not needed and should be reduced or even prohibited as it does not improve yields but stimulates the emission of the strong GHG N2O.

Donor-Derived CD7 CAR-T Therapy Followed by Allogeneic Hematopoietic Stem Cell Transplantation for Acute T-Lymphocytic Leukemia Associated With Hepatitis B: A Case Report.

The use of chimeric antigen receptor T cells (CAR-Ts) is effective in the treatment of hematological malignancies. It has been reported that HBV is reactivated after CAR-T immunotherapy for refractory/relapsed hematological malignant B-cell tumors. However, there is little literature on donor-derived CAR-T therapy combined with allogeneic hematopoietic stem cell transplantation in hepatitis B patients with acute T-lymphocytic leukemia. We report the case of one patient with hepatitis B associated with relapsed/refractory acute T-lymphocytic leukemia (T-ALL) treated with donor-derived CD7 CAR-T therapy and allogeneic hematopoietic stem cell transplantation. During treatment, the copy number of hepatitis B virus continuously decreased, and AST, ALT, DBIL and TBIL remained within the controllable ranges. CD7-negative MRD recurred 4.5 months after transplantation, and the flow cytometry results became negative after immunosuppressive reduction. Seven months after transplantation, the patient had complete remission, and the copy number of hepatitis B virus decreased to below 102. This is the first study on the safety and effectiveness of donor-derived CD7 CAR-T therapy bridging to allogeneic hematopoietic stem cell transplantation in a patient with relapsed/refractory acute T-lymphocytic leukemia and hepatitis B.

Reduced fertilization mitigates N2O emission and drip irrigation has no impact on N2O and NO emissions in plastic-shed vegetable production in northern China.

Plastic-shed vegetable production in China creates hotspots for emission of the potent greenhouse gas nitrous oxide (N2O) and the atmospheric pollutant nitric oxide (NO). To mitigate N2O and NO emissions, determination of the predominant processes of N2O and NO generation in plastic-shed vegetable production is important. Here, we reported the findings of a 2-year experimental study on the effects of reduced fertilization and/or drip irrigation on N2O and NO emissions during plastic-shed tomato production in northern China. Five treatments were applied: 1) over fertilization and flood irrigation (conventional practice); 2) fertilization reduced by 20% and flood irrigation; 3) fertilization reduced by 20% and drip irrigation; 4) fertilization reduced by 30% and drip irrigation, and 5) control (no fertilizer input and flood irrigation). Reduced both basal and top-dressed fertilization maintained tomato yields. Compared with conventional practices (mean annual N2O and NO emissions: 18.1 ± 1.3 and 0.79 ± 0.02 kg N ha-1 yr -1, respectively), fertilization reduction by 20%-30% decreased the annual N2O emission by 21.2%-27.0% owing to lower soil inorganic nitrogen (SIN) contents under the reduced fertilization practices. Switching from flood to drip irrigation might weaken denitrification due to lower soil moisture and less wet soil area, but increased SIN contents, and thus had no significant impact on annual N2O and NO emissions. Peak N2O fluxes occurred at soil temperature 28 °C and water-filled pore space (WFPS) > 60%, were higher than those for NO, and peak NO fluxes appeared 4-6 days later than N2O fluxes, consistent with the decline in WFPS. These observations indicated that N2O and NO from alkaline plastic-shed soil may be mainly generated via heterotrophic denitrification and nitrification, respectively. Reduced fertilization and drip irrigation in plastic-shed tomato production maintained crop productivity and mitigated N2O emission. These results could be integrated into the decision-making in sustainable plastic-shed production.

Impact of anaerobic soil disinfestation on seasonal N2O emissions and N leaching in greenhouse vegetable production system depends on amount and quality of organic matter additions.

Greenhouse vegetable production (GVP) systems in China receive excessive amounts of fertilizers (>1500 kg N ha-1 yr-1) and irrigation (>1200 mm yr-1), which results in severe soil degradation. Moreover, soil borne diseases are common as the same crop is planted continuously over years. Anaerobic soil disinfestation (ASD) is a method carried out every 3-4 years during the summer fallow period to combat soil-borne diseases and to improve soil health. The standard ASD practice, which is carried out before the cropping season, involves incorporation of organic matter (i.e. rice shells or straw) into the soil, covering of the soil with plastic films and soil irrigation until saturation. However, many farmers incorporate large amounts of organic nitrogen fertilizer for priming ASD. In this study, we investigated if incorporation of rice shells plus chicken manure (ASD+RM; farmers practice) provokes higher environmental N losses (N2O emissions and N leaching) during the ASD and the following tomato crop growing period as compared to the standard ASD practice (ASD+R: only rice shells) or a Control (fallow, but with incorporation of organic manure, standard in non-ASD years). Results showed that ASD+RM increased seasonal (ASD/fallow period plus tomato crop growing period) soil N2O emissions by a factor of 3 (ASD+RM: 14.1 kg N2O-N ha-1; ASD+R: 4.7 kg N2O-N ha-1), with 2/3 of emissions occurring during the 25 days long ASD period. Across all treatments, nitrate (NO3-) leaching dominated total N leaching (75%), with significantly lower rates observed for ASD+R as compared to ASD+RM. For both ASD treatments, total dissolved organic nitrogen (DON) leaching was a factor of two higher than for the Control. Crop productivity was not affected by ASD. Our findings imply that ASD+RM should be abandoned as the additional supply of manure N results in high environmental N losses without further increasing yields.

Adjuvant Therapy for Resectable Biliary Tract Cancer: A Bayesian Network Analysis.

Background: Selecting proper postoperative adjuvant therapy is of great importance for prolonging overall survival (OS) of patients with biliary tract cancer (BTC). OS is commonly affected by high rate of postoperative recurrence and metastasis. Purpose: The present study aimed to identify the optimal adjuvant therapy for BTC patients. Method: A comprehensive search was carried out on Pubmed, Web of science, and Embase databases to acquire articles regarding BTC therapy approaches. Subsequently, the hazard ratio (HR) and its 95% confidence intervals (CIs) were applied to evaluate the efficacy of different adjuvant therapy regimens. The GemTc (GemTc.0.8-2) and R (R.3.6.0) software were employed to perform statistical analyses. Result: Data from 22 articles, including 14,646 patients, were quantitatively analyzed. The results showed that in terms of 5-year OS, gemcitabine (GEM) was considered as the optimal adjuvant therapy for BTC compared with chemoradiotherapy (CRT; HR = 0.59; 95% CI = 0.34-0.97), observation (OB; HR = 0.49; 95% CI = 0.33-0.73), and radiotherapy (RT; HR = 0.40; 95% CI = 0.22-0.71). Additionally, 5-fluorouracil (5-FU) exhibited improved efficacy compared with RT (HR = 0.52; 95% CI = 0.29-0.91) and OB (HR = 0.63; 95% CI = 0.43-0.92). When the efficacy of 5-FU was compared with that of GEM, the results showed that 5-FU (HR = 1.29) was more effective than GEM. Furthermore, CRT and RT prolonged positive resection margin (R+)-OS (HR = 0.69; 95% CI = 0.49-1.00) and positive lymph node-(N+)-OS (HR = 0.22; 95% CI = 0.074-0.66) in BTC patients. In terms of median recurrence-free survival (RFS) and 1-year OS, the differences were not statistically significant among different therapeutic interventions. Conclusion: The present study suggested that GEM could be used as a first-line adjuvant therapy for resected BTC patients. Additionally, CRT could be the optimal treatment approach for R+ and N+ patients.

Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker for Patients With Metastatic Renal Cell Carcinoma Treated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

There is increasing evidence to suggest that the neutrophil-to-lymphocyte ratio (NLR) is related to the prognosis of patients with renal cell carcinoma (RCC) treated with immune checkpoint inhibitors (ICIs). However, these findings are inconsistent. The present study was performed with the aim of exploring the utility of NLR in patients with RCC treated with ICIs. For this purpose, a comprehensive search of PubMed, Web of Science, and Embase was performed to find studies evaluating the prognostic value of NLR. The overall survival (OS) and progression-free survival (PFS) were the assessed clinical outcomes. All statistical analysis was performed using Stata version 12.0 software. The combined hazard ratios (HRs) and 95% confidence intervals (CIs) of NLR for OS and PFS were calculated using the random-effect models. Heterogeneity was evaluated based on the I 2 value and Cochran's Q test. Egger's and Begg's tests were applied to precisely assess the publication bias. The "trim and fill" method was adopted to perform the sensitivity analysis to determine whether the results were stable. In total, 12 studies encompassing 1,275 patients were included in the final analysis. The results revealed that a high NLR at baseline or pre-therapy was associated with a poor OS (HR, 2.23; 95% CI, 1.84-2.70; p < 0.001) and PFS (HR, 1.78; 95% CI, 1.72-2.09; p < 0.001). During the course of treatment, a decrease in the NLR was associated with a significantly longer OS (HR, 0.34; 95% CI, 0.20-0.56; p < 0.001) and PFS (HR, 0.44; 95% CI, 0.30-0.63; p < 0.001) compared to an increase in NLR. As a preliminary screening of other risk factors, age, sex, race, and IMDC risk may have a certain prognostic value for RCC treated with ICIs. People over 70 years old had better OS compared to people younger than 70 (HR, 0.65; 95% CI, 0.48-0.89). Non-Caucasians treated with immunotherapy had a worse OS (HR, 8.67; 95% CI, 2.87-26.2) and PFS (HR, 2.65; 95% CI, 1.28-5.48) than Caucasians. Males had a worse OS than females (HR, 1.48; 95% CI, 1.14-1.93). Compared with the IMDC favorable risk group, the OS of the IMDC poor risk group was worse (HR, 2.59; 95% CI, 1.56-4.32). There was no significant publication bias or heterogeneity observed in the present study. On the whole, the present study demonstrated that an elevated NLR is associated with an adverse OS and PFS in patients with RCC treated with ICIs. The NLR may thus be used as a readily available prognostic biomarker for these patients. Age, sex, race, and IMDC risk may have potential predictive value for the prognosis of RCC treated with ICIs. However, further investigations are warranted to validate these results.

Crop straw incorporation alleviates overall fertilizer-N losses and mitigates N2O emissions per unit applied N from intensively farmed soils: An in situ 15N tracing study.

A thorough elucidation of the coupled effects of N fertilization and straw incorporation on N2O emissions and N losses is crucial for alleviating negative environmental impacts in intensively farmed regions. Here, we conducted an in situ 15N tracing experiment to assess the source of N2O emissions and fate of fertilizer-N in soil intensively farmed with summer maize (Zea mays L.). Four treatments, i.e., no N fertilization and no straw incorporation (N0S0), straw incorporation only (N0S1), N fertilization only (N1S0), and N fertilization plus straw incorporation (N1S1), were established in the study. Compared with straw removal, straw incorporation increased the seasonal N2O emissions by 22.3% but reduced the N2O emissions per unit of applied N by 6.22% (P > 0.05). The emission of fertilizer-derived N2O occurred mainly in the 13-17 days after fertilization; thereafter, the ratio of fertilizer-derived N2O fluxes would be less than 5%. N fertilization significantly stimulated non-fertilizer-derived N2O emissions and soil CO2 fluxes, especially when straw was incorporated (P < 0.05), indicating that N fertilization might have triggered the mineralization of straw-N and/or native soil organic N. The soil NO3--N concentration in straw-incorporated plots tended to be lower than that in straw-removed plots, especially after N fertilization events. Straw incorporation sequestered 52.5% (27.4 kg N ha-1) more fertilizer-N in 1 m of soil than straw removal (P < 0.05) while significantly increasing the fertilizer-N harvest index and maintaining grain yield. Overall, compared with straw removal, straw incorporation significantly reduced total fertilizer-N losses (by 12.8%, i.e., 14.58 kg N ha-1; P < 0.05). Our study highlights the benefits of straw incorporation for increasing in-season and multiseason fertilizer-N use efficiencies and alleviating fertilizer-N-induced environmental costs in intensively farmed regions.

[How Different Ratios of Straw Incorporation to Nitrogen Fertilization Influence Endogenous and Exogenous Carbon Release from Agricultural Soils].

The adjustment of the C/N ratio by straw combined with fertilizer nitrogen (N) not only affects straw decomposition but also affects soil organic carbon (SOC) decomposition, i.e. the priming effects. Therefore, it is doubly important to study how the ratios of straw to N fertilizer influence the release of endogenous and exogenous C for greenhouse gas emission reduction and soil fertility improvement. We conducted a 32-week laboratory incubation experiment with 13C labeled maize straw under different N levels in farmland soil collected from fields in Huantai County to investigate the effect of the ratios of straw to N fertilizer on straw decomposition and the priming effects. Four treatments were set up, including CK, corn straw (S), corn straw+low urea rates (SN1), and corn straw+high urea rates (SN2). Dynamic sampling was conducted during the early stage (0-10 d), the middle stage (11-43 d), and the later stage (44-224 d) of straw decomposition. The approach was based on using a two-source mixing model to differentiate two sources of soil CO2 (straw and soil-derived C). With an increase in the incubation time, the contribution of SOC decomposition to soil CO2 emissions first decreased and then increased. On the contrary, the contribution of straw mineralization to soil CO2 emissions first increased and then decreased. By the end of the incubation time, the contribution of SOC and straw decomposition to soil CO2 emissions was 0.84-0.86 and 0.14-0.16, respectively. Over the whole incubation period, the effects of N fertilization on straw decomposition first increased and then decreased. The promotion degree of high and low N fertilization on straw decomposition was up to 15.8% and 7.9%, respectively. Over the whole incubation period, the inhibition degree of low N fertilization reached up to 7.1%, while high N fertilization showed a slight promotion trend of 0.7%. Therefore, the regulation of C:N by straw combined with fertilizer N not only affected the contribution of exogenous straw to SOC but also influenced the decomposition of endogenous SOC, and then influenced soil C fixation. Over the whole incubation period, straw C retention could not compensate for CO2 released by the priming effects, which led to a net loss of SOC.

Influences of irrigation and fertilization on soil N cycle and losses from wheat-maize cropping system in northern China.

Excess of water irrigation and fertilizer consumption by crops has resulted in high soil nitrogen (N) losses and underground water contamination not only in China but worldwide. This study explored the effects of soil N input, soil N output, as well as the effect of different irrigation and N- fertilizer managements on residual N. For this, two consecutive years of winter wheat (Triticum aestivum L.) -summer maize (Zea mays L.) rotation was conducted with: N applied at 0 kg N ha-1 yr-1, 420 kg N ha-1 yr-1 and 600 kg N ha-1 yr-1 under fertigation (DN0, DN420, DN600), and N applied at 0 kg N ha-1 yr-1 and 600 kg N ha-1 yr-1 under flood irrigation (FN0, FN600). The results demonstrated that low irrigation water consumption resulted in a 57.2% lower of irrigation-N input (p < 0.05) in DN600 when compared to FN600, especially in a rainy year like 2015-2016. For N output, no significant difference was found with all N treatments. Soil gaseous N losses were highly correlated with fertilization (p < 0.001) and were reduced by 23.6%-41.7% when fertilizer N was decreased by 30%. Soil N leaching was highly affected by irrigation and a higher reduction was observed under saving irrigation (reduced by 33.9%-57.3%) than under optimized fertilization (reduced by 23.6%-50.7%). The net N surplus was significantly increased with N application rate but was not affected by irrigation treatments. Under the same N level (600 kg N ha-1 yr-1), fertigation increased the Total Nitrogen (TN) stock by 17.5% (0-100 cm) as compared to flood irrigation. These results highlighted the importance to further reduction of soil N losses under optimized fertilization and irrigation combined with N stabilizers or balanced- N fertilization for future agriculture development.

Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes.

OBJECTIVE: Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role. METHODS: Fresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined. RESULTS: TIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells. CONCLUSION: The results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS.