The OsNLP3/4-OsRFL module regulates nitrogen-promoted panicle architecture in rice.

Rice panicles, a major component of yield, are regulated by phytohormones and nutrients. How mineral nutrients promote panicle architecture remains largely unknown. Here, we report that NIN-LIKE PROTEIN3 and 4 (OsNLP3/4) are crucial positive regulators of rice panicle architecture in response to nitrogen (N). Loss-of-function mutants of either OsNLP3 or OsNLP4 produced smaller panicles with reduced primary and secondary branches and fewer grains than wild-type, whereas their overexpression plants showed the opposite phenotypes. The OsNLP3/4-regulated panicle architecture was positively correlated with N availability. OsNLP3/4 directly bind to the promoter of OsRFL and activate its expression to promote inflorescence meristem development. Furthermore, OsRFL activates OsMOC1 expression by binding to its promoter. Our findings reveal the novel N-responsive OsNLP3/4-OsRFL-OsMOC1 module that integrates N availability to regulate panicle architecture, shedding light on how N nutrient signals regulate panicle architecture and providing candidate targets for the improvement of crop yield.

Significant methane ebullition from large shallow eutrophic lakes of the semi-arid region of northern China.

Eutrophic lakes are a major source of the atmospheric greenhouse gas methane (CH4), and CH4 ebullition emissions from inland lakes have important implications for the carbon cycle. However, the spatio-temporal heterogeneity of CH4 ebullition emission and its influencing factors in shallow eutrophic lakes of arid and semi-arid regions remain unclear. This study aimed to determine the mechanism of CH4 emission via eutrophication in Lake Ulansuhai, a large shallow eutrophic lake in a semi-arid region of China.To this end, monthly field surveys were conducted from May to October 2021, and gas chromatography was applied using the headspace equilibrium technique with an inverted funnel arrangement. The total CH4 fluxes ranged from 0.102 mmol m-2 d-1 to 59.296 mmol m-2 d-1 with an average value of 4.984 ± 1.82 mmol m-2 d-1. CH4 ebullition emissions showed significant temporal and spatial variations. The highest CH4 ebullition emission was observed in July with a grand mean of 9.299 mmol m-2 d-1, and the lowest CH4 ebullition emissions occurred in October with an average of 0.235 mmol m-2 d-1. Among seven sites (S1-S7), the maximum (3.657 mmol m-2 d-1) and minimum (1.297 mmol m-2 d-1). CH4 ebullition emissions were observed at S2 and S7, respectively. As the main route of CH4 emission to the atmosphere in Lake Ulansuhai, the CH4 ebullition flux during May to October accounted for 69% of the total CH4 flux. Statistical analysis showed that CH4 ebullition was positively correlated with temperature (R = 0.391, P < 0.01) and negatively correlated with air pressure (R = 0.286, P < 0.00). Temperature and air pressure were found to strongly regulate the production and oxidation of CH4. Moreover, nutritional status indicators such as TP and NH4+-N significantly affect CH4 ebullition emissions (R = 0.232, P < 0.01; R = -0.241, P < 0.01). This study reveals the influencing factors of CH4 ebullition emission in Lake Ulansuhai, and provides theoretical reference and data support for carbon emission from eutrophic lakes. Nevertheless, research on eutrophic shallow lakes needs to be further strengthened. Future research should incorporate improved flux measurement techniques with process-based models to improve the accuracy from regional to large-scale estimation of CH4 emissions and clarify the carbon budget of aquatic ecosystems. In this manner, the understanding and predictability of CH4 ebullition emission from shallow lakes can be improved.

Balanced nitrogen-iron sufficiency boosts grain yield and nitrogen use efficiency by promoting tillering.

Crop yield plays a critical role in global food security. For optimal plant growth and maximal crop yields, nutrients must be balanced. However, the potential significance of balanced nitrogen-iron (N-Fe) for improving crop yield and nitrogen use efficiency (NUE) has not previously been addressed. Here, we show that balanced N-Fe sufficiency significantly increases tiller number and boosts yield and NUE in rice and wheat. NIN-like protein 4 (OsNLP4) plays a pivotal role in maintaining the N-Fe balance by coordinately regulating the expression of multiple genes involved in N and Fe metabolism and signaling. OsNLP4 also suppresses OsD3 expression and strigolactone (SL) signaling, thereby promoting tillering. Balanced N-Fe sufficiency promotes the nuclear localization of OsNLP4 by reducing H2O2 levels, reinforcing the functions of OsNLP4. Interestingly, we found that OsNLP4 upregulates the expression of a set of H2O2-scavenging genes to promote its own accumulation in the nucleus. Furthermore, we demonstrated that foliar spraying of balanced N-Fe fertilizer at the tillering stage can effectively increase tiller number, yield, and NUE of both rice and wheat in the field. Collectively, these findings reveal the previously unrecognized effects of N-Fe balance on grain yield and NUE as well as the molecular mechanism by which the OsNLP4-OsD3 module integrates N-Fe nutrient signals to downregulate SL signaling and thereby promote rice tillering. Our study sheds light on how N-Fe nutrient signals modulate rice tillering and provide potential innovative approaches that improve crop yield with reduced N fertilizer input for benefitting sustainable agriculture worldwide.

The ABI3-ERF1 module mediates ABA-auxin crosstalk to regulate lateral root emergence.

Abscisic acid (ABA) is involved in lateral root (LR) development, but how ABA signaling interacts with auxin signaling to regulate LR formation is not well understood. Here, we report that ABA-responsive ERF1 mediates the crosstalk between ABA and auxin signaling to regulate Arabidopsis LR emergence. ABI3 is a negative factor in LR emergence and transcriptionally activates ERF1 by binding to its promoter, and reciprocally, ERF1 activates ABI3, which forms a regulatory loop that enables rapid signal amplification. Notably, ABI3 physically interacts with ERF1, reducing the cis element-binding activities of both ERF1 and ABI3 and thus attenuating the expression of ERF1-/ABI3-regulated genes involved in LR emergence and ABA signaling, such as PIN1, AUX1, ARF7, and ABI5, which may provide a molecular rheostat to avoid overamplification of auxin and ABA signaling. Taken together, our findings identify the role of the ABI3-ERF1 module in mediating crosstalk between ABA and auxin signaling in LR emergence.

Transcription elongation factor AtSPT4-2 positively modulates salt tolerance in Arabidopsis thaliana.

BACKGROUND: Salt stress significantly influences plant growth and reduces crop yield. It is highly anticipated to develop salt-tolerant crops with salt tolerance genes and transgenic technology. Hence, it is critical to identify salt tolerance genes that can be used to improve crop salt tolerance. RESULTS: We report that the transcription elongation factor suppressor of Ty 4-2 (SPT4-2) is a positive modulator of salt tolerance in Arabidopsis thaliana. AtSPT4-2 expression is induced by salt stress. Knockout mutants of AtSPT4-2 display a salt-sensitive phenotype, whereas AtSPT4-2 overexpression lines exhibit enhanced salt tolerance. Comparative transcriptomic analyses revealed that AtSPT4-2 may orchestrate the expression of genes associated with salt tolerance, including stress-responsive markers, protein kinases and phosphatases, salt-responsive transcription factors and those maintaining ion homeostasis, suggesting that AtSPT4-2 improves salt tolerance mainly by maintaining ion homeostasis and enhancing stress tolerance. CONCLUSIONS: AtSPT4-2 positively modulates salt tolerance by maintaining ion homeostasis and regulating stress-responsive genes and serves as a candidate for the improvement of crop salt tolerance.

A new method based on additive vegetation index for mapping Huangtai algae coverage in Lake Ulansuhai.

Huangtai algal blooms are key indicators of eutrophication and lake-ecosystem damage. Understanding the spatiotemporal heterogeneity of their growth is critical for preserving the ecological environment. The dimidiate pixel model is commonly used to estimate vegetation coverage; however, indices such as the normalized difference vegetation index have not been specifically constructed for the Huangtai algae spectrum and thus are not specific or sufficiently precise for use as indicators. Therefore, we propose a new dimidiate pixel model based on a novel additive vegetation index to calculate the Huangtai algal coverage for each pixel using Landsat multispectral satellite images with 30-m resolution. The results showed that the additive vegetation index with R2 = 0.994 is a better indicator than the normalized difference vegetation index, enhanced vegetative index, and ratio vegetative index, with the accuracy of the new model reaching 86.61%. Monthly Landsat images from 2006 to 2016 were used to calculate the Huangtai algal coverage. Analysis of the inter-monthly variation indicated increased coverage from May to July, with an annual maximum and minimum of 14.43% and 0.33% in 2008 and 2013, respectively. This study provides a new reference map of Huangtai algal cover, which is important for monitoring and protecting the Lake Ulansuhai environment.

The CARD8 T60 variant associates with NLRP1 and negatively regulates its activation.

The NLRP1 inflammasome functions as canonical cytosolic sensor in response to intracellular infections and is implicated in auto-inflammatory diseases. But the regulation and signal transduction mechanisms of NLRP1 are incompletely understood. Here, we show that the T60 variant of CARD8, but not the canonical T48 isoform, negatively regulates the NLRP1 inflammasome activation by directly interacting with the receptor molecule NLRP1 and inhibiting inflammasome assembly. Furthermore, our results suggest that different ASC preference in three types of inflammasomes, namely the ASC-indispensable NLRP1 inflammasome, ASC-dispensable mNLRP1b inflammasome and ASC-independent CARD8 inflammasome, is mainly caused by the CARD domain, not the UPA subdomain. Based on the systematic site-directed mutagenesis and structural analysis, we find that signal transduction of the NLRP1 inflammasome relies on multiple interaction surfaces at its CARD domain. Finally, our results partly explain how mutations in NLRP1 lead to its constitutive activation in auto-inflammatory diseases. In conclusion, our study not only reveals how CARD8 downregulates the NLRP1 inflammasome activation, but also provides insights into the assembly mechanisms of CARD-containing inflammasomes.

Drivers of spatial and seasonal variations of CO2 and CH4 fluxes at the sediment water interface in a shallow eutrophic lake.

Shallow eutrophic lakes contribute disproportional to the emissions of CO2 and CH4 from inland waters. The processes that contribute to these fluxes, their environmental controls, and anthropogenic influences, however, are poorly constrained. Here, we studied the spatial variability and seasonal dynamics of CO2 and CH4 fluxes across the sediment-water interface, and their relationships to porewater nutrient concentrations in Lake Ulansuhai, a shallow eutrophic lake located in a semi-arid region in Northern China. The mean concentrations of CO2 and CH4 in porewater were 877.8 ± 31.0 µmol L-1 and 689.2 ± 45.0 µmol L-1, which were more than 50 and 20 times higher than those in the water column, respectively. The sediment was always a source of both gases for the water column. Porewater CO2 and CH4 concentrations and diffusive fluxes across the sediment-water interface showed significant temporal and spatial variations with mean diffusive fluxes of 887.3 ±124.7 µmol m-2 d-1 and 607.1 ± 68.0 µmol m-2 d-1 for CO2 and CH4, respectively. The temporal and spatial variations of CO2 and CH4 concentrations in porewater were associated with corresponding variations in dissolved organic carbon and dissolved nitrogen species. Temperature and dissolved organic carbon in surface porewater were the most important drivers of temporal variations in diffusive fluxes, whereas dissolved organic carbon and nitrogen were the main drivers of their spatial variations. Diffusive fluxes generally increased with increasing dissolved organic carbon and nitrogen in the porewater from the inflow to the outflow region of the lake. The estimated fluxes of both gases at the sediment-water interface were one order of magnitude lower than the emissions at the water surface, which were measured in a companion study. This indicates that diffusive fluxes across the sediment-water interface were not the main pathway for CO2 and CH4 emissions to the atmosphere. To improve the mechanistic understanding and predictability of greenhouse gas emissions from shallow lakes, future studies should aim to close the apparent gap in the CO2 and CH4 budget by combining improved flux measurement techniques with process-based modeling.

Rice NIN-LIKE PROTEIN 3 modulates nitrogen use efficiency and grain yield under nitrate-sufficient conditions.

Nitrogen (N) is an essential macronutrient for crop growth and yield. Improving the N use efficiency (NUE) of crops is important to agriculture. However, the molecular mechanisms underlying NUE regulation remain largely elusive. Here we report that the OsNLP3 (NIN-like protein 3) regulates NUE and grain yield in rice under N sufficient conditions. OsNLP3 transcript level is significantly induced by N starvation and its protein nucleocytosolic shuttling is specifically regulated by nitrate. Loss-of-function of OsNLP3 reduces plant growth, grain yield, and NUE under sufficient nitrate conditions, whereas under low nitrate or different ammonium conditions, osnlp3 mutants show no clear difference from the wild type. Importantly, under sufficient N conditions in the field, OsNLP3 overexpression lines display improved grain yield and NUE compared with the wild type. OsNLP3 orchestrates the expression of multiple N uptake and assimilation genes by directly binding to the nitrate-responsive cis-elements in their promoters. Overall, our study demonstrates that OsNLP3, together with OsNLP1 and OsNLP4, plays overlapping and differential roles in N acquisition and NUE, and modulates NUE and the grain yield increase promoted by N fertilizer. Therefore, OsNLP3 is a promising candidate gene for the genetic improvement of grain yield and NUE in rice.

Arabidopsis MADS-box factor AGL16 is a negative regulator of plant response to salt stress by downregulating salt-responsive genes.

Sessile plants constantly experience environmental stresses in nature. They must have evolved effective mechanisms to balance growth with stress response. Here we report the MADS-box transcription factor AGL16 acting as a negative regulator in stress response in Arabidopsis. Loss-of-AGL16 confers resistance to salt stress in seed germination, root elongation and soil-grown plants, while elevated AGL16 expression confers the opposite phenotypes compared with wild-type. However, the sensitivity to abscisic acid (ABA) in seed germination is inversely correlated with AGL16 expression levels. Transcriptomic comparison revealed that the improved salt resistance of agl16 mutants was largely attributed to enhanced expression of stress-responsive transcriptional factors and the genes involved in ABA signalling and ion homeostasis. We further demonstrated that AGL16 directly binds to the CArG motifs in the promoter of HKT1;1, HsfA6a and MYB102 and represses their expression. Genetic analyses with double mutants also support that HsfA6a and MYB102 are target genes of AGL16. Taken together, our results show that AGL16 acts as a negative regulator transcriptionally suppressing key components in the stress response and may play a role in balancing stress response with growth.

Homotypic CARD-CARD interaction is critical for the activation of NLRP1 inflammasome.

Cytosolic inflammasomes are supramolecular complexes that are formed in response to intracellular pathogens and danger signals. However, as to date, the detailed description of a homotypic caspase recruitment domain (CARD) interaction between NLRP1 and ASC has not been presented. We found the CARD-CARD interaction between purified NLRP1CARD and ASCCARD experimentally and the filamentous supramolecular complex formation in an in vitro proteins solution. Moreover, we determined a high-resolution crystal structure of the death domain fold of the human ASCCARD. Mutational and structural analysis revealed three conserved interfaces of the death domain superfamily (Type I, II, and III), which mediate the assembly of the NLRP1CARD/ASCCARD complex. In addition, we validated the role of the three major interfaces of CARDs in assembly and activation of NLRP1 inflammasome in vitro. Our findings suggest a Mosaic model of homotypic CARD interactions for the activation of NLRP1 inflammasome. The Mosaic model provides insights into the mechanisms of inflammasome assembly and signal transduction amplification.

Rice NIN-LIKE PROTEIN 4 plays a pivotal role in nitrogen use efficiency.

Nitrogen (N) is one of the key essential macronutrients that affects rice growth and yield. Inorganic N fertilizers are excessively used to boost yield and generate serious collateral environmental pollution. Therefore, improving crop N use efficiency (NUE) is highly desirable and has been a major endeavour in crop improvement. However, only a few regulators have been identified that can be used to improve NUE in rice to date. Here we show that the rice NIN-like protein 4 (OsNLP4) significantly improves the rice NUE and yield. Field trials consistently showed that loss-of-OsNLP4 dramatically reduced yield and NUE compared with wild type under different N regimes. In contrast, the OsNLP4 overexpression lines remarkably increased yield by 30% and NUE by 47% under moderate N level compared with wild type. Transcriptomic analyses revealed that OsNLP4 orchestrates the expression of a majority of known N uptake, assimilation and signalling genes by directly binding to the nitrate-responsive cis-element in their promoters to regulate their expression. Moreover, overexpression of OsNLP4 can recover the phenotype of Arabidopsis nlp7 mutant and enhance its biomass. Our results demonstrate that OsNLP4 plays a pivotal role in rice NUE and sheds light on crop NUE improvement.

Use of integrated biomarker response for evaluating antioxidant stress and DNA damage of earthworms (Eisenia fetida) in decabromodiphenyl ethane-contaminated soil.

Decabromodiphenyl ethane (DBDPE) is a new and popular type of brominated flame retardant (BFR) with high bromine content, strong thermal stability, and ultraviolet resistance. To evaluated the potential toxicity of this new BFR to soil ecosystem, different concentrations of DBDPE were used to observe effects on earthworms (Eisenia fetida) in artificial soil. The reactive oxygen species (ROS) contents, activities of antioxidase system and detoxify enzyme, levels of malondialdehyde (MDA), as well as DNA damage in earthworms were measured after exposure to 0, 2.5, 5, 10, and 20 mg/kg DBDPE in artificial soil for 7, 14, 21, and 28 days. The results showed that ROS and MDA content significantly increased for all treatments from days 7-21, followed by a decrease. Throughout the experimental period, SOD, POD, and CAT activities increased. The GST activity was stimulated significantly from days 14-28. Besides, the olive tail moment (OTM) value in all treated groups was significantly higher than that in the control and exhibited a concentration-related and exposure time-related response. This is the first study evaluating the biological toxicity of BFR at different concentrations using an integrated biomarker response index. Our results show that DBDPE has biochemical toxicity on earthworms, which sheds some light on the potential risks of DBDPE in the soil environment and provides a basis for the monitoring and diagnosis of soils contaminated with DBDPE.

Evaluation of the clinical application of multiple tumor marker protein chip in the diagnostic of lung cancer.

BACKGROUND: The early diagnostic of lung cancer plays an important role in the prognosis of surgical treatment among lung cancer patients. To evaluate the clinical application of multi-tumor markers protein biochip in the diagnosis of lung cancer, 12 tumor markers were detected in patients with different stages of lung cancer. METHODS: Serum CA125, CA19-9, Ferritin, CA15-3, CA242, CEA, AFP, NSE, PSA, f-PSA, HGH, and ß-HGH were assessed in 506 patients, with 224 patients with lung cancer (including 123 cases of adenocarcinoma, 30 squamous cell carcinoma, 54 small-cell carcinoma, and 17 non classification), 159 patients with benign lung disease and 90 healthy people control by the C-12 multiple tumor protein-chip detective system. RESULTS: The positive rate of C-12 (77.23%) in lung cancer was significantly higher than that of benign lung disease (13.84%) and healthy people (9.76%) (P < .01). In lung cancer, the positive rate of CA199, NSE, CEA, CA242, Ferritin, f-PSA, and CA125 were significantly higher than that of benign lung disease and healthy people. In adenocarcinoma, the positive rate of CA125 (73.53%) was significantly higher than that of squamous cell carcinoma (36.67%) and small-cell carcinoma (56.62%). CONCLUSION: The C-12 multiple tumor protein-chip detective system has acceptable sensitivity in the diagnostic of lung cancer.

Exogenous melatonin enhances salt stress tolerance in maize seedlings by improving antioxidant and photosynthetic capacity.

Melatonin (N-acetyl-5-methoxytryptamine) is an important biological hormone in many abiotic stress responses and developmental processes. In this study, the protective roles of melatonin were investigated by measuring the antioxidant defense system and photosynthetic characteristics in maize under salt stress. The results indicated that NaCl treatment led to the decrease in plant growth, chlorophyll contents and photochemical activity of photosystem II (PSII). However, the levels of reactive oxygen species increased significantly under salt stress. Meanwhile, we found that application of exogenous melatonin alleviated reactive oxygen species burst and protected the photosynthetic activity in maize seedlings under salt stress through the activation of antioxidant enzymes. In addition, 100 µM melatonin-treated plants showed high photosynthetic efficiency and salinity. Immunoblotting analysis of PSII proteins showed that melatonin application alleviated the decline of 34 kDa PSII reaction center protein (D1) and the increase of PSII subunit S protein. Taken together, our study promotes more comprehensive understanding in the protective effects of exogenous melatonin in maize under salt stress, and it may be involved in activation of antioxidant enzymes and regulation of PSII proteins.

Biomarker responses of earthworms (Eisenia fetida) to soils contaminated with perfluorooctanoic acid.

Perfluorooctanoic acid (PFOA) is considered a persistent environmental pollutant. The aim of this study was to assess the potential toxicity of PFOA to earthworms (Eisenia fetida) in artificial soil. The activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione S-transferase (GST) as well as the contents of malondialdehyde (MDA) were measured after exposure to 0, 5, 10, 20, and 40 mg kg-1 PFOA in soils for 7, 14, 21, and 28 days. The results showed that SOD activity increased at 14 days and decreased from 21 to 28 days; MDA levels were highest in the treatment with 40 mg kg-1 PFOA after 28 days of exposure. In contrast, CAT and POD activities increased after 14-21 days of exposure and significantly decreased with long-term exposure (28 days). GST activity increased significantly from 14 to 28 days. Our results indicate that PFOA has biochemical effects on E. fetida, thereby contributing to our understanding of the ecological toxicity of PFOA on soil invertebrates.

Extraction, antioxidant and antibacterial activities of Broussonetia papyrifera fruits polysaccharides.

Polysaccharides were extracted from Broussonetia papyrifera ((L.) L'Herit. ex Vent.) fruits (BPP), and response surface methodology was used to maximize extraction yield. The optimum extraction conditions were: ratio of water to solid, 30mL/g; extraction duration, 50min; extraction power, 180W; and extraction temperature, 60°C. Under these conditions, the yield of BPP was 8.61%. Then, BPP was purified, and three purified fractions (designated BPP-1, BPP-2 and BPP-3) were obtained for further physicochemical properties, antioxidant activity and antibacterial activity analysis. These fractions were mainly composed of glucose, mannose and arabinose residue, meanwhile, BPP-3 had a significantly higher rhamnose and uronic acid content than BPP-1 and BPP-2. And BPP-3 showed the best hydroxyl radial scavenging activity, ferric reducing activity power (FRAP), antihemolytic activity and antibacterial activity.

Prevalence and genotype distribution of human papillomavirus among women from Henan, China.

Human papillomavirus (HPV) infection has been implicated as a causative of cervical cancer. In the present study, a total of 578 samples from females attending the gynecological outpatient clinic in Henan province, China, were collected and the HPV genotypes were detected by gene chip and flow-through hybridization. Overall, 44.5% (257/578) females were found to be HPV DNA positive, and the high risk HPV (HR-HPV) rate was 35.1% (203/578). The first peak of HR-HPV infection appeared in the >60 year-old group (55.0%), and the second was within the 51-55 year-old group (50.0%) (χ2=19.497, p<0.05). HPV 16 was the most prevalent genotype (9.2%), followed by HPV 52 (7.8%), HPV 6 (6.9%), HPV 11 (5.9%) and HPV 42 (5.0%). The single type HPV infection was 30.4%, with the five majority prevalent genotype HPV 16 (16.5%), HPV 52 (14.3%), HPV 6 (12.6%), HPV 42 (8.6%), HPV 31 (5.1%). The multiple-type HPV infections were 14.0%, and HPV 16 was the most prevalent type (29.6%), followed by HPV 52 (24.7%), HPV 6 (22.2%), HPV 11 (22.2%), HPV 42 (17.3%) and HPV 39 (17.3%).

First line chemotherapy with weekly docetaxel and cisplatin in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study.

INTRODUCTION: We report outcomes for a phase II study of the combination of weekly docetaxel and cisplatin in elderly patients with advanced non-small cell lung cancer. METHODS: Patients with chemotherapy-naive, stage IIIB/IV, an Eastern Cooperative Oncology Group performance status of 0 or 1, ages 70 years or older, were eligible. Chemotherapy consisted of cisplatin (25 mg/m2) on days 1, 8, and 15 and docetaxel (20 mg/m2) on days 1, 8, and 15 every 4 weeks. RESULTS: Forty-six (95.8%) of the 48 patients were assessable for response, 1 case of complete response and 18 cases of partial response were confirmed, giving an overall response rate of 39.6% (95% confidence interval [CI], 25.7-53.5%). The median time to progression and overall survival for all patients was 5.0 months (95% CI, 4.1-5.7 months) and 10.9 months (95% CI, 9.6-12.2 months), respectively. The most severe hematologic adverse event was anemia, which occurred with grade 3 intensity in 6 (13.0%) patients and grade 4 in 2 (4.3%) patients. Neutropenia occurred with grade 3 intensity in 4 (8.7%) patients. Grade 3 asthenia, diarrhea, neuropathy, stomatitis, and nausea/vomiting were observed in 2 (4.3%), 5 (10.9%), 5 (10.9%), 5 (10.9%), and 3 (6.5%) patients, respectively. Yet, no grade 4 nonhematologic toxicity was observed. CONCLUSIONS: The combination of weekly docetaxel and cisplatin is a well-tolerated treatment modality with encouraging activity and survival outcome in previously untreated elderly patients with advanced non-small cell lung cancer.