Applications and prospects of cryo-EM in drug discovery.

Drug discovery is a crucial part of human healthcare and has dramatically benefited human lifespan and life quality in recent centuries, however, it is usually time- and effort-consuming. Structural biology has been demonstrated as a powerful tool to accelerate drug development. Among different techniques, cryo-electron microscopy (cryo-EM) is emerging as the mainstream of structure determination of biomacromolecules in the past decade and has received increasing attention from the pharmaceutical industry. Although cryo-EM still has limitations in resolution, speed and throughput, a growing number of innovative drugs are being developed with the help of cryo-EM. Here, we aim to provide an overview of how cryo-EM techniques are applied to facilitate drug discovery. The development and typical workflow of cryo-EM technique will be briefly introduced, followed by its specific applications in structure-based drug design, fragment-based drug discovery, proteolysis targeting chimeras, antibody drug development and drug repurposing. Besides cryo-EM, drug discovery innovation usually involves other state-of-the-art techniques such as artificial intelligence (AI), which is increasingly active in diverse areas. The combination of cryo-EM and AI provides an opportunity to minimize limitations of cryo-EM such as automation, throughput and interpretation of medium-resolution maps, and tends to be the new direction of future development of cryo-EM. The rapid development of cryo-EM will make it as an indispensable part of modern drug discovery.

Large cystic-solid pulmonary hamartoma: A case report.

BACKGROUND: It now seems that all pulmonary hamartomas (PHs) are large cystic-solid lesions that are difficult to diagnose. However, few cases of large cystic-solid PHs have been reported. The present case report presents a large cystic-solid PH and provides a literature review of the imaging features, formation mechanism and histopathological basis of PHs. CASE SUMMARY: A 53-year-old woman with no clinical symptoms underwent a chest computed tomography (CT) examination at our hospital. Nonenhanced CT images revealed a large, flat tumor with multiple air-containing cysts in the left thoracic cavity and a cystic part confined to the medial side of the tumor; the solid part of the tumor showed abundant fat and lamellar soft tissue components. Multiple small blood vessels were detected in the solid part of the tumor on contrast-enhanced CT images. Given the large size of the lesion, the patient elected to undergo surgery. Histological examination revealed PH. A detailed review of the patient's CT imaging showed that the lesion had a small vascular pedicle to the left lower lobe, which was a clue to its lung tissue histological origin. According to immunohistochemical staining, the confined multiple air-containing cysts were caused by the entrapment of respiratory/alveolar epithelium. CONCLUSION: This case shows the imaging manifestations of a large PH. Heightened awareness of its formation mechanism and histopathological basis may alert radiologists to consider this diagnosis in their daily workflow.

Subchronic Oral Toxicity Evaluation of Sodium Dehydroacetate: A 90-day Repeated Dose Study in Rats.

Objective: The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake. Methods: DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD. Results: Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight. Conclusion: The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.

Lipid Accumulation and IL-6 Production in L02 Hepatocytes Induced by Sodium Oleate: Dose and Time Dependence.

To explore interleukin-6 (IL-6) production and characterize lipid accumulation in L02 hepatocytes induced by sodium oleate. L02 hepatocytes were incubated with 0, 37.5, 75, 150, 300, 600, or 1,200 µmol/L sodium oleate for 24 h, and the supernatant was collected to detect the concentration of IL-6. L02 hepatocytes were incubated with 300, 150, 75, or 0 µmol/L sodium oleate for 0-24 h. The supernatant was collected for detection of IL-6 and free fatty acids. L02 hepatocytes treated with 300 µmol/L sodium oleate for 0-24 h were stained with Oil Red O. With extended sodium oleate incubation time, IL-6 levels increased, and free fatty acids decreased. After 24 h incubation, IL-6 levels increased as sodium oleate increased from 37.5 to 300 µmol/L ( P < 0.05 for 37.5 µmol/L, P < 0.01 for 75 µmol/L and P < 0.001 for concentrations 150 µmol/L or higher). Lipid accumulation increased as the sodium oleate concentration and incubation time increased. Oil Red O staining intensified with incubation time extending beyond 2 h. IL-6 production and lipid accumulation in L02 hepatocytes are influenced by sodium oleate in a dose- and time-dependent manner.

Subchronic toxicity of cerium nitrate by 90-day oral exposure in wistar rats.

This study evaluated the subchronic toxicity of cerium nitrate and determined the no observed adverse effect level (NOAEL) in Wistar rats. In accordance with the Organization for Economic Co-operation and Development guidelines, cerium nitrate was orally administered to Wistar rats by gavage at 0, 0.2, 75, 150, and 300 mg/kg bw/day for 90 days, followed by 28 days of recovery period in the 300 mg/kg bw/day and the control groups. The following parameters were evaluated: mortality, abnormalities, body weight, food consumption, hematology, serum biochemistry, urinanalysis, gross necropsy and histopathology. At the end of the treatment, several significant changes were observed in the 300 mg/kg bw/day groups: relatively decreased mean body weight of males, increased LYMPH%, RET% and decreased NEUT%, RBC of the females, increased ALT, AST and decreased ALB, T-Bil, CHO, CK, LDH of males. Significantly decreased T-Bil, CHO, CK and LDH were also observed in males of the 150 mg/kg bw/day group. Pathological examination revealed that the incidences of foreign body granulomatous lesions in lungs were higher in the 150 and 300 mg/kg bw/day groups as compared with the control group. These findings were attributed to unexpected gavage exposure because the granuloma exhibited a bronchiole-derived distribution. Taken together, the NOAEL of cerium nitrate in Wistar rats is set to be 75 mg/kg bw/day in the present study.

Radiologic features of Castleman's disease involving the renal sinus: A case report and review of the literature.

BACKGROUND: We present a rare case of plasma cell type of Castleman's disease (CD) involving only the right renal sinus in a 65-year-old woman with a duplex collecting system (DCS). CASE SUMMARY: The patient presented with a right renal sinus lesion after renal ultrasonography. Subsequent abdominal enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of the kidneys showed DCS and a soft tissue mass with mild enhancement at the lower right renal sinus. The lesion was suspected to be a malignant renal pelvic carcinoma. Hence, the patient underwent a right radical nephrectomy. Histological examination revealed hyperplastic lymphoid follicles in the renal sinus. A detailed review of the patient's CT and MRI images and a literature review suggested that the lesion was hypointense on T2-weighted images and hyperintense on diffusion-weighted image manifestations, and showed mild enhancement, which distinguished the plasma cell type of CD from many other renal sinus lesions. Furthermore, peripelvic soft tissue masses with a smooth internal surface of the renal pelvis were on imaging findings, which suggests that the urinary tract epithelial system is invulnerable and can be used to differentiate the plasma cell type of CD from malignant lymphoma with a focally growth pattern to some extent. CONCLUSION: Preoperative diagnosis is often difficult in such cases, as plasma cell type of CD involving only the right kidney is exceedingly rare. However, heightened awareness of this disease entity and its radiographic presentations may alert one to consider this diagnosis.

Evaluation of behavioral profiles in mice fed with milk supplemented diets derived from human lactoferrin gene-modified cows.

To date, many safety assessments of genetically modified (GM) food have been done, but there was still considerable skepticism about the safety of genetic modified foods because no study could be designed to discover all of the potential effects. Since behavioral endpoints could provide one of the most sensitive strategies to reveal subtle functional deficits. In the present study, behavioral profiles in mice fed with milk derived from human lactoferrin gene-modified cows were investigated to enrich the toxicological data of GM food. Conventional milk and GM milk were added to diets at a proportion of 7.5%, 15% and 30%(w/w). After the mice consuming different diets for 30 days, a battery of behavioral tests were conducted to evaluate motor, sensory and cognitive functions. No significant differences were observed in spontaneous activity, grip strength and nociception between the treatment groups. And animals of different groups exhibited similar performance in rotarod, dark box, step-down and MORRIS water maze task. The study suggested that mice fed with conventional milk or human lactoferrin gene-modified milk had similar motor, sensory and cognitive functions.

Subchronic Oral Toxicity Evaluation of Lanthanum: A 90-day, Repeated Dose Study in Rats.

OBJECTIVE: The present study was undertaken to evaluate the subchronic toxicity of lanthanum and to determine the no observed adverse effect level (NOAEL), which is a critical factor in the establishment of an acceptable dietary intake (ADI). METHODS: In accordance with the Organization for Economic Co-operation and Development (OECD) testing guidelines, lanthanum nitrate was administered once daily by gavage to Sprague-Dawley (SD) rats at dose levels of 0, 1.5, 6.0, 24.0, and 144.0 mg/kg body weight (BW) per day for 90 days, followed by a recovery period of 4 weeks in the 144.0 mg/kg BW per day and normal control groups. Outcome parameters were mortality, clinical symptoms, body and organ weights, serum chemistry, and food consumption, as well as ophthalmic, urinary, hematologic, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate a point of departure for the hazard risk assessment of lanthanum. RESULTS: Significant decreases were found in the 144.0 mg/kg BW group in the growth index, including body weight, organ weights, and food consumption. This study suggests that the NOAEL of lanthanum nitrate is 24.0 mg/kg BW per day. Importantly, the 95% lower confidence value of the benchmark dose (BMDL) was estimated as 9.4 mg/kg BW per day in females and 19.3 mg/kg BW per day in males. CONCLUSION: The present subchronic oral exposure toxicity study may provide scientific data for the risk assessment of lanthanum and other rare earth elements (REEs).

Subchronic Oral Toxicity of Silica Nanoparticles and Silica Microparticles in Rats.

OBJECTIVE: To investigate the subchronic oral toxicity of silica nanoparticles (NPs) and silica microparticles (MPs) in rats and to compare the difference in toxicity between two particle sizes. METHODS: Sprague-Dawley rats were randomly divided into seven groups: the control group; the silica NPs low-, middle-, and high-dose groups; and the silica MPs low-, middle-, and high-dose groups [166.7, 500, and 1,500 mg/(kg•bw•day)]. All rats were gavaged daily for 90 days, and deionized water was administered to the control group. Clinical observations were made daily, and body weights and food consumption were determined weekly. Blood samples were collected on day 91 for measurement of hematology and clinical biochemistry. Animals were euthanized for necropsy, and selected organs were weighed and fixed for histological examination. The tissue distribution of silicon in the blood, liver, kidneys, and testis were determined. RESULTS: There were no toxicologically significant changes in mortality, clinical signs, body weight, food consumption, necropsy findings, and organ weights. Differences between the silica groups and the control group in some hematological and clinical biochemical values and histopathological findings were not considered treatment related. The tissue distribution of silicon was comparable across all groups. CONCLUSION: Our study demonstrated that neither silica NPs nor silica MPs induced toxicological effects after subchronic oral exposure in rats.

Subchronic toxicity study of yttrium nitrate by 90-day repeated oral exposure in rats.

Concerns regarding the adverse effects of long-term exposure to low levels of rare earth elements (REEs) from foods on human health have arisen in recent years. Nevertheless, no official acceptable daily intake (ADI) has yet been proposed for either total REEs or individual REE. In accordance with the Organization for Economic Co-operation and Development (OECD) testing guideline, the present study was undertaken to evaluate the subchronic toxicity of yttrium, a representative heavy REE with higher contaminated level in foods in China, to achieve a no observed adverse effect level (NOAEL) which is a critical basis for the establishment of an ADI. Yttrium nitrate was orally administered to rats at doses of 0, 10, 30 and 90 mg/kg/day for 90 days followed by a recovery period of 4 weeks. The following toxicity indices were measured: mortality, clinical signs, daily food consumption and weekly body weight; urinalysis, hematology, blood coagulation, clinical biochemistry and histopathology at the end of administration and recovery periods. No toxicologically significant changes were found in any yttrium-treated group as compared to the concurrent control group. Under the present experimental condition, the NOAEL in rats was thus set at 90 mg/kg for yttrium nitrate, i.e. 29.1 mg/kg for yttrium.

Effects of Parental Dietary Exposure to GM Rice TT51 on the Male Reproductive System of Rat Offspring.

OBJECTIVE: To evaluate the health effects of parental dietary exposure to GM rice TT51 on the male reproductive system of rat off spring. METHODS: Rice-based diets, containing 60% ordinary grocery rice, MingHui63, or TT51 by weight, were given to parental rats (15 males/30 females each group) for 70 days prior mating and throughout pregnancy and lactation. After weaning, eight male offspring rats were randomly selected at each group and fed with diets correspondent to their parents' for 70 days. The effects of exposure to TT51 on male reproductive system of offspring rats were assessed through sperm parameters, testicular function enzyme activities, serum hormones (FSH, LH, and testosterone levels), testis histopathological examination, and the relative expression levels of selected genes along the hypothalamic-pituitary- testicular (HPT) axis. RESULTS: No significant differences were observed in body weight, food intake, organ/body weights, serum hormone, sperm parameters, testis function enzyme ACP, LDH, and SDH activities, testis histopathological changes, and relative mRNA expression levels of GnRH-R, FSH-R, LH-R, and AR along the HPT axis. CONCLUSION: The results of this study demonstrate that parental dietary exposure to TT51 reveals no significant differences on the reproductive system of male offspring rats compared with MingHui63 and control.

Neurobehavioral Assessment of Rats Exposed to Yttrium Nitrate during Development.

OBJECTIVE: The aim of this study was to assess the effects of yttrium nitrate on neurobehavioral development in Sprague-Dawley rats. METHODS: Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day (GD) 6 to postnatal day (PND) 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. RESULTS: No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. CONCLUSION: Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.

Effects of application of corn straw on soil microbial community structure during the maize growing season.

This study investigated the influence of corn straw application on soil microbial communities and the relationship between such communities and soil properties in black soil. The crop used in this study was maize (Zea mays L.). The five treatments consisted of applying a gradient (50, 100, 150, and 200%) of shattered corn straw residue to the soil. Soil samples were taken from May through September during the 2012 maize growing season. The microbial community structure was determined using phospholipid fatty acid (PLFA) analysis. Our results revealed that the application of corn straw influenced the soil properties and increased the soil organic carbon and total nitrogen. Applying corn straw to fields also influenced the variation in soil microbial biomass and community composition, which is consistent with the variations found in soil total nitrogen (TN) and soil respiration (SR). However, the soil carbon-to-nitrogen ratio had no effect on soil microbial communities. The abundance of PLFAs, TN, and SR was higher in C1.5 than those in other treatments, suggesting that the soil properties and soil microbial community composition were affected positively by the application of corn straw to black soil. A Principal Component Analysis indicated that soil microbial communities were different in the straw decomposition processes. Moreover, the soil microbial communities from C1.5 were significantly different from those of CK (p < 0.05). We also found a high ratio of fungal-to-bacterial PLFAs in black soil and significant variations in the ratio of monounsaturated-to-branched fatty acids with different straw treatments that correlated with SR (p < 0.05). These results indicated that the application of corn straw positively influences soil properties and soil microbial communities and that these properties affect these communities. The individual PLFA signatures were sensitive indicators that reflected the changes in the soil environment condition.

Endocrine disruption of cadmium in rats using the OECD enhanced TG 407 test system.

OBJECTIVE: To evaluate the endocrine disrupting effects of cadmium (Cd) using OECD enhanced TG407 test guideline. METHODS: Sprague-Dawley (SD) rats were randomly divided into six groups and accordingly administered with 0, 1, 2.5, 5, 10, 20 mg/kg•BW/day of Cd by gavage for 28 days. Body weight, food consumption, hematology, biochemistry, sex hormone levels, urinary ß2-microglobulin, organ weights and histopathology and estrous cycle were detected. RESULTS: Cd could significantly decrease animals' body weight (P<0.05). Serum luteinizing hormone (LH) at 10-20 mg/kg•BW groups and testosterone (T) at 2.5 and 10 mg/kg•BW groups decreased significantly (P<0.05). However, no statistically significant change was found in urinary ß2-microglobulin among Cd-treatment groups (P>0.05). Endpoints related to female reproduction including uterus weight and histopathological change at 10-20 mg/kg•BW groups showed significant increase (P<0.05). While among male rats in 2.5, 10, 20 mg/kg•BW groups, weight of prostate, thyroids, and seminal vesicle glands significantly decreased (P<0.05). Moreover, no histopathological change was observed in kidney. CONCLUSION: Results suggested that Cd can cause endocrine disrupting effects in SD rats. Comparing with possible renal toxicity of Cd, its toxicity on endocrine system was more sensitive.

Immunotoxicity of acrylamide in female BALB/c mice.

OBJECTIVE: To investigate the immunotoxicity of acrylamide (ACR) in female BALB/c mice. METHODS: A total of 200 female mice weighing 18-22 g were randomly divided into four clusters based on body weight, and each weight-based cluster included five groups (10 mice per group): negative control, positive control (cyclophosphamide), low, intermediate, and high dose ACR groups, and all the groups were administered ACR by gavage for 30 days. At the end of the study, the immunotoxicological effects of the ACR were evaluated through immunopathology, humoral immunity, cellular immunity, and non-specific immunity. RESULTS: The terminal body weight, spleen and thymus weights, lymphocyte counts in the ACR-H group were decreased, pathological changes were observed in lymph glands, thymus and spleen. %T cells in blood lymphocytes were significantly increased in all ACR-treated groups, and a significant reduction of % natural killer(NK) cells and increase of %Th cells were observed in the ACR-H group. interleukin-6(IL-6), Concanavalin A(ConA)-induced splenocyte proliferation and serum half hemolysis value (HC50) were also significantly suppressed in the ACR-H group. CONCLUSION: ACR elicited an inhibitory effect on cellular and humoral immunity of mice after 30 day feeding.

A two-generation reproduction study with transgenic Bt rice TT51 in Wistar rats.

TT51 is a transgenic Bt rice created by fusion a synthetic CryAb/CryAc gene into rice MingHui63. A significant number of animal feeding studies with transgenic crops have been carried out with the rapid development of transgenic crops. However, the evidence is far from identifying whether certain novel transgenic crops possess potential danger for human or animal health after long-term consumption. Rice-based diets, containing 60% ordinary grocery rice, MingHui63 rice or TT51 rice by weight, were fed to two generations of male and female rats in order to determine the potential reproductive effects of TT51. In this study, both clinical performance variables and histopathological responses were examined and compared between groups. There were no significant differences between groups on body weights, food consumption, reproductive data and relative organ/body weights. There were some statistically significant differences in hematology and serum chemistry parameters, but no histological abnormalities were seen in the brain, heart, liver, spleen, kidneys, stomach, small intestine, thymus, ovaries, uterus, testes and epididymides. Based on the results, under the circumstance of this study TT51 show no significant differences on reproduction performance of rats compared with MingHui63 and the control.

Immunotoxicological evaluation of wheat genetically modified with TaDREB4 gene on BALB/c mice.

OBJECTIVE: To evaluate the immunotoxicological effects of genetically modified wheat with TaDREB4 gene in female BALB/c mice. METHODS: Female mice weighing 18-22 g were divided into five groups (10 mice/group), which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control group and positive control group were fed with AIN93G diet, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (the proportion is 76%) for 30 days, then body weight, absolute and relative weight of spleen and thymus, white blood cell count, histological examination of immune organ, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell, serum half hemolysis value, mitogen-induced splenocyte proliferation, delayed-type hypersensitivity reaction and phagocytic activities of phagocytes were detected. RESULTS: No immunotoxicological effects related to the consumption of the genetically modified wheat were observed in BALB/c mice when compared with parental wheat group, common wheat group and negative control group. CONCLUSION: From the immunotoxicological point of view, results from this study demonstrate that genetically modified wheat with TaDREB4 gene is as safe as the parental wheat.

Combined subchronic toxicity of bisphenol A and dibutyl phthalate on male rats.

OBJECTIVE: To evaluate the combined subchronic toxicity of bisphenol A (BPA) and dibutyl phthalate (DBP) in male Sprague Dawley (SD) rats. METHODS: Forty 4-week-old male rats weighing 115-125 g were randomly divided into BPA-treated, DBP-treated group, BPA+DBP-treated and control groups and fed with a soy- and alfalfa-free diet containing 285.4 ppm BPA, 285.4 ppm DBP, 285.4 ppm BPA plus 285.4 ppm DBP, and a control diet, respectively, for 90 consecutive days. At the end of the study, the animals were sacrificed by exsanguination via the carotid artery under diethyl etherane aesthesia and weighed. Organs, including liver, kidneys, spleen, thymus, heart, brain, and testis underwent pathological examination. The androgen receptor (AR), gonadotropin-releasing hormone receptor (GNRHR), and progesterone hormone receptor (PR) genes from the hypothalamus were detected by real-time PCR. The biomedical parameters were analyzed. RESULTS: No significant difference was found in food intake, body weight, tissue weight, organ/brain weight ratio, and biomedical parameters among the four groups (P>0.05). However, BPA and DBP up-regulated AR, PR and GNRHR expression levels in rats and showed a synergistic or an additive effect in the BPA+DBP group. CONCLUSION: The combined subchronic toxicity of BPA and DBP is synergistic or additive in male SD rats.

[Immunotoxicologic assessment of genetically modified drought-resistant wheat T349 with GmDREB1].

OBJECTIVE: To assess the immunotoxicologic effects of genetically modified drought resistant wheat T349 with GmDREB1 gene. METHODS: A total of 250 female BALB/c mice (6-8 week-old, weight 18-22 g) were divided into five large groups (50 mice for each large group) by body weight randomly. In each large group, the mice were divided into five groups (10 mice for each group) by body weight randomly, which were set as negative control group, common wheat group, parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, respectively. Mice in negative control and positive control group were fed with feedstuff AIN-93G, mice in common wheat group, non-genetically modified parental wheat group and genetically modified wheat group were fed with feedstuffs added corresponding wheat (proportion up to 76%) for 30 days, then body weight, organ coefficient of spleen and thymus, peripheral blood lymphocytes phenotyping, serum cytokine, serum immunoglobulin, antibody plaque-forming cell (PFC), serum 50% hemolytic value (HC50), mitogen-induced splenocyte proliferation, delayed-type hypersensitivity (DTH) reaction and phagocytic activities of phagocytes were detected respectively. RESULTS: After 30 days raise, among negative control group, common wheat group, non-genetically modified parental wheat group, genetically modified wheat group and cyclophosphamide positive control group, mice body weight were (21.0±0.3), (20.4±0.7), (21.1±1.0), (21.1±1.0), (19.4±1.0) g, respectively (F=7.47, P<0.01); organ coefficient of spleen were (0.407±0.047)%, (0.390±0.028)%, (0.402±0.042)%, (0.421±0.041)%, (0.304±0.048)%, respectively (F=12.41, P<0.01); organ coefficient of thymus were (0.234±0.032)%, (0.246±0.028)%, (0.249±0.040)%, (0.234±0.034)%, (0.185±0.039)%, respectively (F=5.58, P<0.01); the percentage of T cell in peripheral blood were (70.43±4.44)%, (68.33±5.37)%, (73.04±2.68)%, (74.42±2.86)%, (90.42±1.66)%, respectively (F=57.51, P<0.01); the percentage of B cell were (13.89±3.19)%, (15.34±4.84)%, (13.06±4.22)%, (12.93±2.36)%, (3.01±0.96)%, respectively (F=12.79, P<0.01); the percentage of Th cell were (55.87±3.80)%, (55.24±4.60)%, (57.92±3.70)%, (59.57±2.54)%, (77.37±2.31)%, respectively (F=68.58, P<0.01);the Th/Ts ratio were 4.16±0.29, 4.73±0.96, 4.19±0.78, 4.52±0.40, 6.34±0.73, respectively (F=17.57, P<0.01);the serum IgG were (1046.38±210.67), (1065.49±297.22), (1517.73±299.52), (1576.67±241.92), (1155.88±167.05) µg/ml, respectively (F=10.53, P<0.01); the serum IgM were (333.83±18.97), (327.73±27.72), (367.47±27.18), (363.42±46.14), (278.71±24.42) µg/ml, respectively (F=12.11, P<0.01); the serum IgA were (51.69±10.10), (42.40 ± 8.35), (32.11±4.22), (37.12±4.90), (41.45±8.89) µg/ml, respectively (F=8.25, P<0.01); the PFC were (29.2±14.6), (28.0±20.0), (34.8±30.9), (33.2±25.1), (4.8±5.3) per 10(6) splenocyte, respectively (F=3.33, P<0.05); the HC50 were 82.3±6.5, 79.7±4.6, 75.8±4.1, 74.9±3.6, 70.8±2.1, respectively (F=9.99, P<0.01);the LPS-induced splenocyte proliferation were 0.21±0.10, 0.21±0.14, 0.26±0.12, 0.25±0.14, 0.07±0.06, respectively (F=4.18, P<0.05). CONCLUSION: The genetically modified drought-resistant wheat T349 was substantially equivalent to parental wheat in the effects on immune organs and immunologic functions of mice, and it didn't show immunotoxicity.