Using new indices to predict metabolism dysfunction-associated fatty liver disease (MAFLD): analysis of the national health and nutrition examination survey database.

BACKGROUND: Metabolism dysfunction-associated fatty liver disease (MAFLD), is the most common chronic liver disease. Few MAFLD predictions are simple and accurate. We examined the predictive performance of the albumin-to-glutamyl transpeptidase ratio (AGTR), plasma atherogenicity index (AIP), and serum uric acid to high-density lipoprotein cholesterol ratio (UHR) for MAFLD to design practical, inexpensive, and reliable models. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2007-2016 cycle dataset, which contained 12,654 participants, was filtered and randomly separated into internal validation and training sets. This study examined the relationships of the AGTR and AIP with MAFLD using binary multifactor logistic regression. We then created a MAFLD predictive model using the training dataset and validated the predictive model performance with the 2017-2018 NHANES and internal datasets. RESULTS: In the total population, the predictive ability (AUC) of the AIP, AGTR, UHR, and the combination of all three for MAFLD showed in the following order: 0.749, 0.773, 0.728 and 0.824. Further subgroup analysis showed that the AGTR (AUC1 = 0.796; AUC2 = 0.690) and the combination of the three measures (AUC1 = 0.863; AUC2 = 0.766) better predicted MAFLD in nondiabetic patients. Joint prediction outperformed the individual measures in predicting MAFLD in the subgroups. Additionally, the model better predicted female MAFLD. Adding waist circumference and or BMI to this model improves predictive performance. CONCLUSION: Our study showed that the AGTR, AIP, and UHR had strong MAFLD predictive value, and their combination can increase MAFLD predictive performance. They also performed better in females.

Seasonal variations in the relationship between sun-induced chlorophyll fluorescence and photosynthetic capacity from the leaf to canopy level in a rice crop.

Photosynthetic capacity (leaf maximum carboxylation rate, Vcmax) is a critical parameter for accurately assessing carbon assimilation by plant canopies. Recent studies of sun-induced chlorophyll fluorescence (SIF) have shown potential for estimating Vcmax at the ecosystem level. However, the relationship between SIF and Vcmax at the leaf and canopy levels is still poorly understood. In this study, we investigated the dynamic relationship between SIF and Vcmax and its controlling factors using SIF and CO2 response measurements in a rice paddy. We found that SIF and its yield (SIFy) were strongly correlated with Vcmax during the growing season, although the relationship varied with plant growth stages. After flowering, SIFy showed a stronger relationship with Vcmax than SIF flux at both the leaf and canopy levels. Further analysis suggested that the divergence of the link between SIF and Vcmax from leaf to canopy are the result of changes in canopy structure and leaf physiology, highlighting that these need to be considered when interpreting the SIF signal across spatial scales. Our results provide evidence that remotely sensed SIF observations can be used to track seasonal variations in Vcmax at the leaf and canopy levels.

Ultrasound Elastic Parameters Predict Central Lymph Node Metastasis of Papillary Thyroid Carcinoma.

BACKGROUND: This study aimed to explore the new factors that can predict central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) independently from ultrasound characteristics, elastic parameters, and endocrine indicators. METHODS: A total of 391 patients with PTC undergoing thyroidectomy and prophylactic central lymph node dissection from January 2017 to June 2019 were collected to determine the independent predictors of CLNM by single-factor and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed 9 independent predictors of CLNM, age, male, tumors in the middle or lower poles (without tumors in the isthmus), tumors in the isthmus, multiple tumors, and maximum tumor diameter measured by ultrasound, microcalcification, visible surrounding blood flow signal, and the maximum value of elastic modulus (Emax).We used the aforementioned factors to establish a scoring prediction model: predictive score Y(P) = 1/[1 + exp (1.444 + 0.084 ∗ age - 0.834 ∗ men - 0.73 ∗ multifocality - 2.718 ∗ tumors in the isthmus - 0.954 ∗ tumors in the middle or lower poles - 0.086 ∗ tumor maximum diameter - 1.070 ∗ microcalcification - 0.892 ∗ visible surrounding blood flow signal - 0.021 ∗ Emax)]. The area under the curve of the receiver operating characteristic was 0.827. It was found that 0.524 was the highest index of Youden, and the best cutoff value for predicting CLNM. When Y(P)≥0.524, the risk of CLNM in patients with PTC is predicted to be high. Predictive accuracy was 78.5% and 72.4% in the internal validation group and 78.6% in the external validation group. CONCLUSIONS: These data indicate that the scoring prediction model could provide a scientific and quantitative way to predict CLNM in patients with PTC.

Comparison and application of wavelet transform and Kalman filtering for denoising in δ13CO2 measurement by tunable diode laser absorption spectroscopy at 2.008 µm: retraction.

The referenced article [Opt. Express25, A896 (2017)] has been retracted.

Arabidopsis CALCIUM-DEPENDENT PROTEIN KINASE8 and CATALASE3 Function in Abscisic Acid-Mediated Signaling and H2O2 Homeostasis in Stomatal Guard Cells under Drought Stress.

Drought is a major threat to plant growth and crop productivity. Calcium-dependent protein kinases (CDPKs, CPKs) are believed to play important roles in plant responses to drought stress. Here, we report that Arabidopsis thaliana CPK8 functions in abscisic acid (ABA)- and Ca(2+)-mediated plant responses to drought stress. The cpk8 mutant was more sensitive to drought stress than wild-type plants, while the transgenic plants overexpressing CPK8 showed enhanced tolerance to drought stress compared with wild-type plants. ABA-, H2O2-, and Ca(2+)-induced stomatal closing were impaired in cpk8 mutants. Arabidopsis CATALASE3 (CAT3) was identified as a CPK8-interacting protein, confirmed by yeast two-hybrid, coimmunoprecipitation, and bimolecular fluorescence complementation assays. CPK8 can phosphorylate CAT3 at Ser-261 and regulate its activity. Both cpk8 and cat3 plants showed lower catalase activity and higher accumulation of H2O2 compared with wild-type plants. The cat3 mutant displayed a similar drought stress-sensitive phenotype as cpk8 mutant. Moreover, ABA and Ca(2+) inhibition of inward K(+) currents were diminished in guard cells of cpk8 and cat3 mutants. Together, these results demonstrated that CPK8 functions in ABA-mediated stomatal regulation in responses to drought stress through regulation of CAT3 activity.

Satellite sun-induced chlorophyll fluorescence detects early response of winter wheat to heat stress in the Indian Indo-Gangetic Plains.

Extremely high temperatures represent one of the most severe abiotic stresses limiting crop productivity. However, understanding crop responses to heat stress is still limited considering the increases in both the frequency and severity of heat wave events under climate change. This limited understanding is partly due to the lack of studies or tools for the timely and accurate monitoring of crop responses to extreme heat over broad spatial scales. In this work, we use novel spaceborne data of sun-induced chlorophyll fluorescence (SIF), which is a new proxy for photosynthetic activity, along with traditional vegetation indices (Normalized Difference Vegetation Index NDVI and Enhanced Vegetation Index EVI) to investigate the impacts of heat stress on winter wheat in northwestern India, one of the world's major wheat production areas. In 2010, an abrupt rise in temperature that began in March adversely affected the productivity of wheat and caused yield losses of 6% compared to previous year. The yield predicted by satellite observations of SIF decreased by approximately 13.9%, compared to the 1.2% and 0.4% changes in NDVI and EVI, respectively. During early stage of this heat wave event in early March 2010, the SIF observations showed a significant reduction and earlier response, while NDVI and EVI showed no changes and could not capture the heat stress until late March. The spatial patterns of SIF anomalies closely tracked the temporal evolution of the heat stress over the study area. Furthermore, our results show that SIF can provide large-scale, physiology-related wheat stress response as indicated by the larger reduction in fluorescence yield (SIFyield ) than fraction of photosynthetically active radiation during the grain-filling phase, which may have eventually led to the reduction in wheat yield in 2010. This study implies that satellite observations of SIF have great potential to detect heat stress conditions in wheat in a timely manner and assess their impacts on wheat yields at large scales.

Comparison and application of wavelet transform and Kalman filtering for denoising in δ13CO2 measurement by tunable diode laser absorption spectroscopy at 2.008 µm.

We propose to use the wavelet transform and Kalman filter methods for processing noise in δ13CO2 measurement using laser absorption spectroscopy at 2.008 µm and they have been shown to be useful tool for reducing the intrinsic noise of the optical system. Through the performance comparison and analysis of these two denoising techniques for the intrinsic noise reduction of optical system, it can be found that the Kalman filter is a more suitable approach for the extraction of gas isotope measurement signal from a contaminated signal.

A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats.

AIM: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4-methylpiperazin-1-yl)-coumarin (IMM-H004) has shown anti-apoptotic, anti-inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. METHODS: SD rats were administered IMM-H004 (8 mg·kg(-1)·d(-1), ig) or donepezil (positive control, 1 mg·kg(-1)·d(-1), ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and ß-amyloid (Aß) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. RESULTS: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Aß protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. CONCLUSION: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Aß pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD.

α-Synuclein is prone to interaction with the GC-box-like sequence in vitro.

α-Synuclein (α-syn) is a presynaptic protein that is widely implicated in the pathophysiology of Parkinson's disease, a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons and the formation of Lewy bodies. Evidence suggests that α-syn could be imported into the nucleus and subsequently disrupt normal neuronal function. The existence of α-syn in the nucleus provides the possibility of interaction with DNA leading to gene transcript regulation. Thus, CD spectra were used to determine the specific DNA sequence with which α-syn is most likely to interact. Our results indicated that α-syn was prone to preferentially interact with the GC-box-like sequence in vitro at a ratio of 2:1 or less (α-syn: the GC-box-like sequence).

[Estimation of soil's heavy metal concentrations (As, Cd and Zn) in Wansheng mining area with geochemistry and field spectroscopy].

In the present paper, Chongqing Wansheng mining area was selected as the study area, and the ASD FieldSpec Pro III portable spectroradiometer (350 to 2,500 nm) was used as the spectral measurement instrument to collect the reflectance spectra of 171 soil samples and 123 soil samples in March and in August 2012 respectively. In order to create the retrieval model to retrieve soil heavy metal concentration, 40 among the 123 soil samples in August 2012 were collected to do chemical analysis. Then, the heavy metals' concentration and the reflectance of the 40 soil samples were analyzed together. The results show that the ratio of the reflectance at 2,320 and 1,755 nm in the nearinfrared range, the ratio of the reflectance on 2,260 and 2,210 nm in the nearinfrared range, and the ratio of the reflectance at 480 and 1,920 nm in the visible and near infrared range has a significant correlation with heavy metal concentration of As, Cd and Zn respectively, so the spectral absorption feature parameters (SAFP) for retrieving soil heavy metal concentration of As, Cd and Zn from soil reflectance was created. Thus, the soil heavy metal concentration of As, Cd and Zn of the soil samples can be retrieved with the reflectance spectra. Then the distributions of the soil heavy metal concentration of As, Cd and Zn were obtained with the interpolation method in study area in March and in August 2012 respectively.

Hippocampal transcriptomic analyses reveal the potential antiapoptotic mechanism of a novel anticonvulsant agent Q808 on pentylenetetrazol-induced epilepsy in rats.

Brain apoptosis is one of the main causes of epileptogenesis. The antiapoptotic effect and potential mechanism of Q808, an innovative anticonvulsant chemical, have never been reported. In this study, the seizure stage and latency to reach stage 2 of pentylenetetrazol (PTZ) seizure rat model treated with Q808 were investigated. The morphological change and neuronal apoptosis in the hippocampus were detected by hematoxylin and eosin (HE) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining, respectively. The hippocampal transcriptomic changes were observed using RNA sequencing (RNA-seq). The expression levels of hub genes were verified by quantitative reverse-transcription PCR (qRT-PCR). Results revealed that Q808 could allay the seizure score and prolong the stage 2 latency in seizure rats. The morphological changes of neurons and the number of apoptotic cells in the DG area were diminished by Q808 treatment. RNA-seq analysis revealed eight hub genes, including Map2k3, Nfs1, Chchd4, Hdac6, Siglec5, Slc35d3, Entpd1, and LOC103690108, and nine hub pathways among the control, PTZ, and Q808 groups. Hub gene Nfs1 was involved in the hub pathway sulfur relay system, and Map2k3 was involved in the eight remaining hub pathways, including Amyotrophic lateral sclerosis, Cellular senescence, Fc epsilon RI signaling pathway, GnRH signaling pathway, Influenza A, Rap1 signaling pathway, TNF signaling pathway, and Toll-like receptor signaling pathway. qRT-PCR confirmed that the mRNA levels of these hub genes were consistent with the RNA-seq results. Our findings might contribute to further studies exploring the new apoptosis mechanism and actions of Q808.

Effects of elevated CO2 on the Cd uptake by rice in Cd-contaminated paddy soils.

The rising atmospheric CO2 is a major driver for climate change, directly affects rice production. Cadmium (Cd) in paddy soils also serves as a persistent concern. Currently, few studies consider the rice response to coupled stresses of elevated CO2 (eCO2) and soil Cd. Experimental evidence understanding the effects and mechanisms of eCO2 on Cd uptake by rice is lacking yet. In a free-air CO2 enrichment (FACE) system, a 3-year pot experiment was conducted to explore the Cd uptake by rice under two CO2 conditions (ambient and ambient + 200 µmol·mol-1) using combinations of in-situ Cd-contaminated soils and associated rice varieties. Results showed that more low-crystalline Fe oxides (Feh) in iron plaque (IP) were deposited on root surface with the increased dissolved Fe2+ due to lower soil redox status under eCO2. The Cd accumulation in rice was hindered due to more Cd associated with Feh (Feh-Cd) rather than uptake by roots. Taken together, the relative effects of eCO2 on Cd uptake by rice were consistent across years under different Cd-contaminated soils. Our findings will help to better understand the Cd uptake by rice under future climate conditions, and thus push the development of climate-crop-soil models and accurate prediction for food security.

Does elevated CO2 enhance the arsenic uptake by rice? Yes or maybe: Evidences from FACE experiments.

Elevated CO2 (eCO2) strongly affects rice yield and quality in arsenic (As) paddy soils. However, understanding of the As accumulation in rice under coupled stress of eCO2 and soil As is still limited while data are scarce. It greatly limits the prediction for future rice safety. This study investigated the As uptake by rice grown in different As paddy soils under two CO2 conditions (ambient and ambient +200 µmol mol-1) in the free-air CO2 enrichment (FACE) system. Results showed that eCO2 lowered soil Eh at the tillering stage and caused higher concentrations of dissolved As and Fe2+ in soil pore water. Compared with the control, the increased As transfer abilities in rice straws under eCO2 contributed to the higher As accumulation in rice grains, and their total As concentrations were increased by 10.3-31.2%. Besides, the increased amounts of iron plaque (IP) under eCO2 failed to effectively inhibit the As uptake by rice due to the difference in critical stage between As immobilized by IP (mainly in maturing stage) and uptake by rice roots (about 50% contribution before filling stage). Risk assessments suggest that eCO2 enhanced the human health risks of As intake from rice grains produced in low-As paddy soils (<30 mg kg-1). In order to alleviate the As threats to rice under eCO2, we consider that proper soil drainage before filling stage to improve soil Eh can serve as an effective way to reduce As uptake by rice. Pursuing appropriate rice varieties to reduce the As transfer ability may be the other positive strategy.

Elevated CO2 and temperature under future climate change increase severity of rice sheath blight.

Sheath blight (ShB), caused by Rhizoctonia solani, is one of the major threats to rice (Oryza sativa L.) production. However, it is not clear how the risk of rice ShB will respond to elevated CO2 and temperature under future climate change. Here, we conducted, field experiments of inoculated R. solani under combinations of two CO2 levels (ambient and enriched up to 590 µmol mol-1) and two temperature levels (ambient and increased by 2.0°C) in temperature by free-air CO2 enrichment (T-FACE) system for two cultivars (a susceptible cultivar, Lemont and a resistant cultivar, YSBR1). Results indicate that for the inoculation of plants with R. solani, the vertical length of ShB lesions for cv. Lemont was significantly longer than that for cv. YSBR1 under four CO2 and temperature treatments. The vertical length of ShB lesions was significantly increased by elevated temperature, but not by elevated CO2, for both cultivars. The vertical length of ShB lesions under the combination of elevated CO2 and elevated temperature was increased by 21-38% for cv. Lemont and by -1-6% for cv. YSBR1. A significant increase in MDA level was related to a significant increase in the vertical length of ShB lesions under the combination of elevated CO2 and elevated temperature. Elevated CO2 could not compensate for the negative effect of elevated temperature on yield of both cultivars under future climate change. Rice yield and biomass were further decreased by 2.0-2.5% and 2.9-4.2% by an increase in the severity of ShB under the combination of elevated CO2 and elevated temperature. Thus, reasonable agronomic management practices are required to improve both resistance to ShB disease and grain yield for rice under future climate change.

[Precision measurement of the birefringence of quartz crystal at 1 310 nm based on the spectroscopic ellipsometer].

In order to get the precision measurement of birefringence of quartz crystal at the communication wavelength 1310nm, based on the principle of precision measurement of phase difference between P and S polarized lights of spectroscopic ellipsometer, a method for precision measurement of birefringence of crystal was designed through the analysis of the Jones matrix under the transmission mode, and the precision measurement of birefringence of quartz crystal at 1 310 nm at room temperature (22 degrees C) was made, the measuring results and error analysis show that the precision reached 10(-6) level, this is the most precise birefringence parameter available, and it is of important significance for the improvement of designing precision of phase retardation devices of quartz.

[Immunomodulatory effects of Opuntia dillenii polysaccharides on specific immune function of mice].

OBJECTIVE: To investigate specific immune modulation of Opuntia dillenii polysaccharides (ODPs) on mice (body fluid and cells). METHODS: An immunosuppressed murine model was induced by intraperitoneal injection of cyclophosphamide (Cy, ip). The intraserous hemolysin IgM, IgG levels, the proliferation of spenocytes and the proportion of T lymphocyte subsets in peripheral blood were determined after the mice treated by ODPs. Proliferative effects of ODP-I, the main component purified from ODPs, on the lymphocytes in vitro were also studied. RESULTS: ODPs could significantly increase intraserous IgM and IgG levels, significantly enhance the proliferation of T and B lymphocytes and restore them to normal level. ODPs significantly reduced the percentage of CD4+ T lymphocytes subset, therefore significantly reduced the proportion of CD4+ and CD8+ T lymphocytes of peripheral blood from immunosuppressive mice and restored it to normal level. ODP-I significantly enhanced the natural proliferation of splenic lymphocyte and assisted the proliferation of T and B lymphocytes which induced by mitogen ConA or LPS. CONCLUSION: ODPs can enhance the specific immune function of immunosuppressed mice and the proliferation of lymphocytes in vitro.

Lipid metabolism of cancer stem cells.

Cancer stem cells (CSCs), also termed cancer-initiating cells, are a special subset of cells with high self-replicating and self-renewing abilities that can differentiate into various cell types under certain conditions. A number of studies have demonstrated that CSCs have distinct metabolic properties. The reprogramming of energy metabolism enables CSCs to meet the needs of self-renewal and stemness maintenance. Increasing evidence supports the view that alterations in lipid metabolism, including an increase in fatty acid (FA) uptake, de novo lipogenesis, formation of lipid droplets and mitochondrial FA oxidation, are involved in CSC regulation. In the present review, the metabolic characteristics of CSCs, particularly in lipid metabolism, were summarized. In addition, the potential mechanisms of CSC lipid metabolism in treatment resistance were discussed. Given their significance in cancer biology, targeting CSC metabolism may serve an important role in future cancer treatment.

Disaggregation of Ploidy, Gender, and Genotype Effects on Wood and Fiber Traits in a Diploid and Triploid Hybrid Poplar Family.

Triploid breeding based on unilateral sexual polyploidization is an effective approach for genetic improvement of Populus, which can integrate heterosis and ploidy vigor in an elite variety. However, the phenotypic divergence of unselected allotriploids with the same cross-combination remains poorly understood, and the contributions of ploidy, gender, and genotype effects on phenotypic variation are still unclear. In this study, wood and fiber traits, including basic density (BD), lignin content (LC), fiber length (FL), fiber width (FW), and fiber length/width (FL/W), were measured based on a 10-year-old clonal trial, including full-sib diploid and triploid hybrids of (Populus pseudo-simonii × P. nigra 'Zheyin3#') × P. × beijingensis, and contributions of ploidy, gender, and genotype effects on the variation of these traits, were disaggregated to enhance our understanding of triploid breeding. We found a significant phenotypic variation for all measured traits among genotypes. All the wood and fiber traits studied here underwent strong clonal responses with high repeatabilities (0.55-0.76). The Pearson's correlation analyses based on the best linear unbiased predictors (BLUPs) revealed that BD was significantly positively correlated with FL (r = 0.65, p = 0.030), suggesting that BD could be improved together with FL during triploid breeding. The FL of the triploids was significantly larger than that of the diploids (p < 0.001), suggesting that ploidy strongly affected the variation of FL traits. The difference between females and males was not significant for any measured trait, implying that gender might not be a major factor for variation in these traits. Further analyses of variance components showed that genotype dominantly contributed to the variation of BD, LC, and FW traits (with 54, 62, and 53% contributions, respectively) and ploidy contributed strongly to variation in FL and FL/W (77 and 50%, respectively). The genetic coefficient of variation (CVG) of triploids for each trait was low, suggesting that it is necessary to produce many triploids for selection or to use different Populus species as parents. Our findings provide new insights into the genetic effects of ploidy, gender, and genotype on wood and fiber traits within a full-sib poplar family, enhancing the understanding of the triploid breeding program of Populus.

Curvicladiellapaphiopedili sp. nov. (Hypocreales, Nectriaceae), a new species of orchid (Paphiopedilum sp.) from Guizhou, China.

Background: An asexual fungus, collected from diseased leaves of Paphiopedilum sp. from Guizhou Province, China, and based on the phylogenetic analyses and morphological characters, it was identified as a new species in Curvicladiella. The genus Curvicladiella are recorded for the first time for China. New information: The morphology of Curvicladiellapaphiopedili sp. nov. is characterised by penicillate conidiophores with a stipe, dull, tapering towards the apex, the curved stipe extension and cylindrical conidia. In the phylogenetic analyses of combined cmdA, his3, ITS, LSU, tef1 and tub2 sequence data, this taxon was clustered as sister to Curvicladiellacignea within Nectriaceae.

Activated Stellate Cell Paracrine HGF Exacerbated Pancreatic Cancer Cell Ferroptosis Resistance.

As a refractory tumor, pancreatic carcinoma is more vulnerable to ferroptosis, a novel regulated cell death mode. However, the exact role of pancreatic stellate cells (PSCs) in pancreatic cancer ferroptosis is still unclear. Using the coculture system, we revealed that activated PSCs promote pancreatic cancer cell ferroptosis resistance. Mechanistically, activated PSCs secreted HGF, which further activated the HGF receptor, c-MET, in pancreatic cancer cells, prevented lipid peroxidation, and ultimately triggered pancreatic cancer cell ferroptosis resistance in vitro and in vivo. TCGA and GEPIA databases also revealed a strong correlation between c-MET and antiferroptosis indicators. Our study supplied the evidence for the cross-talk between activated PSCs and pancreatic cancer cells in ferroptosis, which suggested a strategy to inhibit PSC paracrine signaling for preventing pancreatic carcinoma ferroptosis resistance.