A Phase I Study to Evaluate the Safety and Pharmacokinetics of SHR0302 Base Ointment in Healthy Adult Volunteers.

INTRODUCTION: SHR0302 is a highly selective JAK1 inhibitor. This study aimed to investigate the safety, tolerability, and pharmacokinetics of single and multiple-dose topical skin application of SHR0302 base ointment in healthy adult subjects. METHODS: This phase I clinical trial (registration number: CTR20192188) consisted of two parts. Part 1 was a single-dose ascending study with four dose levels in 32 healthy Australian adults (8 subjects in each dose group). All Australian subjects were randomized 3:1 to a single-dose topical skin application of SHR0302 base ointment or placebo. The dose escalated from 1% SHR0302 base ointment on 3% of body surface area (BSA) to 2% SHR0302 base ointment on 20% of BSA. Part 2 combined single and multiple-dose ascension studies with two dose levels in 20 healthy Chinese adults (10 subjects in each dose group). All Chinese subjects were randomized 4:1 to a combination of single and multiple doses for consecutive 10 days of topical application of 1% SHR0302 base ointment on 20% BSA or 2% SHR0302 base ointment on 20% BSA. The safety and pharmacokinetics of the SHR0302 base ointment were evaluated. RESULTS: The incidence of treatment-emergent adverse events (TEAEs) in both parts was comparable between the SHR0302 base ointment group and the vehicle group (part 1: 33.3% vs. 37.5%; part 2: 56.3% vs. 75.0%). All TEAEs were transient, recovered, and equally well-tolerated in the two racial groups. The overall absorption of the SHR0302 base ointment was slow after topical application, with Tmax>10 h. After a single dose of the SHR0302 base ointment, drug exposure in healthy Australian and Chinese subjects increased nonlinearly with the increase in the administration area and drug content. Drug exposure increased in a less-than-dose-proportional manner within the dose range tested. Due to differences in the clinical practice of topical application, the Tmax of the drug in Australian subjects was earlier than in Chinese subjects, but the overall extent of absorption seemed comparable in Australian and Chinese subjects (with comparable AUC0-t). CONCLUSION: The SHR0302 base ointment (either single or multiple doses) was well tolerated and safe, with no racial disparity. KEY MESSAGE: The SHR0302 base ointment (either single or multiples doses) was well tolerated and safe.

Identification of 4-hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation.

BACKGROUND: 4-Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS: Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2 ) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2-(2-amino-4-(4H-1,2,4-triazol-4-yl) benzoyl)-3-hydroxycyclohex-2-en-1-one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION: In this study, five compounds were obtained through multiple quantitative structure-activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low-toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.

Virtual screening based on pharmacophore model for developing novel HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for herbicide design. A multilayered virtual screening workflow was constructed by combining two pharmacophore models based on ligand and crystal complexes, molecular docking, molecular dynamics (MD), and biological activity determination to identify novel small-molecule inhibitors of HPPD. About 110, 000 compounds of Bailingwei and traditional Chinese medicine databases were screened. Of these, 333 were analyzed through docking experiments. Five compounds were selected by analyzing the binding pattern of inhibitors with amino acid residues in the active pocket. All five compounds could produce stable coordination with cobalt ion, and form favorable π-π interactions. MD simulation demonstrated that Phe381 and Phe424 made large contributions to the strength of binding. The enzyme activity experiment verified that compound-139 displayed excellent potency against AtHPPD (IC50 = 0.742 µM), however, compound-5222 had inhibitory effect on human HPPD (IC50 = 6 nM). Compound-139 exhibited herbicidal activity to some extent on different gramineous weeds. This work provided a strong insight into the design and development of novel HPPD inhibitor using in silico techniques.

Ritchey-Common sparse-aperture testing of the Giant Steerable Science Mirror.

The Giant Steerable Science Mirror (GSSM) is the tertiary mirror of the future large telescope, the Thirty Meter Telescope. However, the mirror is too large to be tested using only one aperture, and using many apertures will increase the cost of testing. To accomplish testing at a low cost, the number of apertures should be reduced. The Ritchey-Common (R-C) testing method, commonly used for testing large flat surfaces, uses only a reference spherical mirror and avoids the use of large planar interferometers. Additionally, only the low-spatial-frequency mirror figure is relevant in the system assembly and alignment. Hence, the applicability of sparse-aperture testing is investigated in this paper. Sparse-aperture testing and the R-C method were combined to lower the cost. Using this method and the normalized point source sensitivity (PSSn), the mirror figure can be specified in a simple and accurate manner. Moreover, as fewer subapertures are under test, the efficiency can be improved. An error analysis is conducted, focusing on the shifting error, irregularity error, tipping error, tangential/sagittal error, and seeing. For the testing of the GSSM prototype, the error analysis showed the total error in PSSn is 0.9701.

Analysis and correction for measurement error of edge sensors caused by deformation of guide flexure applied in the Thirty Meter Telescope SSA.

The Thirty Meter Telescope (TMT) project will design and build a 30-m-diameter telescope for research in astronomy in visible and infrared wavelengths. The primary mirror of TMT is made up of 492 hexagonal mirror segments under active control. The highly segmented primary mirror will utilize edge sensors to align and stabilize the relative piston, tip, and tilt degrees of segments. The support system assembly (SSA) of the segmented mirror utilizes a guide flexure to decouple the axial support and lateral support, while its deformation will cause measurement error of the edge sensor. We have analyzed the theoretical relationship between the segment movement and the measurement value of the edge sensor. Further, we have proposed an error correction method with a matrix. The correction process and the simulation results of the edge sensor will be described in this paper.

3D Pharmacophore-Based Virtual Screening and Docking Approaches toward the Discovery of Novel HPPD Inhibitors.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking-based virtual screening were performed to identify novel potential HPPD inhibitors. The complex-based pharmacophore model (CBP) with 0.721 of ROC used for screening compounds showed remarkable ability to retrieve known active ligands from among decoy molecules. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5 (DS 2.5) to discern interactions with key residues at the active site of HPPD. Four compounds with top rankings in the HipHop model and well-known binding model were finally chosen as lead compounds with potential inhibitory effects on the active site of target. The results provided powerful insight into the development of novel HPPD inhibitors herbicides using computational techniques.

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development.

Protective effects of l-carnitine on astheno- and normozoospermic human semen samples during cryopreservation.

This study was conducted to determine the effects of l-carnitine (LC), as an antioxidant, in preventing spermatozoa damage during the freezing-thawing process in both astheno- and normozoospermic human semen samples. Seventy semen samples (37 asthenozoospermic and 33 normozoospermic) were involved in this study. Cryopreservation medium supplemented with 1.0 g/l LC was mixed with semen at a ratio of 1:1 (v/v). Controls were cryopreserved with freezing medium only. Assessment of motility, viability (VIA), mitochondrial membrane potential (MMP) and DNA fragmentation index (DFI) were performed on aliquots of fresh semen, frozen-thawed control and frozen-thawed LC treated samples. Supplementation of the cryopreservation medium with LC induced a significant improvement in post-thaw sperm parameters in both the asthenozoospermic and normozoospermic semen samples, compared with those of the control, regarding sperm fast forward motility, forward motility, total motility and VIA. LC showed better protective effects towards asthenozoospermia for DFI (F = 115.85, P < 0.01) and VIA (F = 67.14, P < 0.01) than did normozoospermic semen samples. We conclude that supplementation with LC prior to the cryopreservation process reduced spermatozoa cryodamage in both asthenozoospermic and normozoospermic semen samples. LC had better protective effects for asthenozoospermic human semen samples. Future research should focus on the molecular mechanism for and the different protective effects of LC between asthenozoospermic and normozoospermic semen samples during cryopreservation.

Value of serum and follicular fluid sirtuin (SIRT)1 and SIRT2 protein levels in predicting the outcome of assisted reproduction.

BACKGROUND: To explore whether serum and follicular fluid (FF), sirtuin 1 (SIRT1), and SIRT2 could predict the outcome of assisted reproduction. METHODS: All patients underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) for the first time in the Reproductive Medicine Center of the First Affiliated Hospital of Zhejiang University Medical College from March 2018 to December 2018. According to cumulative clinical pregnancy outcomes, the patients were divided into a pregnancy group and non-pregnancy group. We measured the serum levels of SIRT1, SIRT2, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) from the second to the fifth day of menstruation, and the levels of SIRT1 and SIRT2 in serum and FF on the day of human chorionic gonadotropin (HCG) injection and oocyte retrieval. RESULTS: A total of 125 patients met the inclusion criteria. The pregnancy group comprised 56 cases and non-pregnancy group 69 cases. There were significant differences in basal level SIRT2 (bSIRT2), AMH, antral follicle count (AFC), number of oocytes obtained, number of mature eggs, number of fertilized eggs, number of excellent embryos, number of blastocyst formations, and number of transferred high-quality embryos between the two groups. The area under the curve (AUC) values of bSIRT2, AFC, AMH, and age were significantly different from those under the opportunity reference line (P<0.05). In the subsequent correlation analysis, FFSIRT2, and HCG day serum SIRT2 were negatively correlated with age (r=-0.35, r=-0.19), and positively correlated with AFC (r=0.2, r=0.02). Serum SIRT1 on HCG day was negatively correlated with the number of blastocysts and the number of frozen embryos (r=-0.18, r=-0.21). Levels of FF SIRT1 and FF SIRT2 were significantly lower than those in serum SIRT1 and SIRT2, and there was no significant difference in serum SIRT1 and SIRT2 before and after ovulation promotion. CONCLUSIONS: The results suggest that bSIRT2 has significant statistical significance in predicting the cumulative number of pregnancies. When combined with AMH, AFC, and age, bSIRT2 can predict the cumulative pregnancy outcome. In addition, the level of serum SIRT1 and SIRT2 were not affected by ovulation promotion.

Elevated CO2 changes the interactions between nematode and tomato genotypes differing in the JA pathway.

Interactions between the root-knot nematode Meloidogyne incognita and three isogenic tomato (Lycopersicon esculentum) genotypes were examined when plants were grown under ambient (370 ppm) and elevated (750 ppm) CO2. We tested the hypothesis that, defence-recessive genotypes tend to allocate 'extra' carbon (relative to nitrogen) to growth under elevated CO2, whereas defence-dominated genotypes allocate extra carbon to defence, and thereby increases the defence against nematodes. For all three genotypes, elevated CO2 increased height, biomass, and root and leaf total non-structural carbohydrates (TNC):N ratio, and decreased amino acids and proteins in leaves. The activity of anti-oxidant enzymes (superoxide dismutase and catalase) was enhanced by nematode infection in defence-recessive genotypes. Furthermore, elevated CO2 and nematode infection did not qualitatively change the volatile organic compounds (VOC) emitted from plants. Elevated CO2 increased the VOC emission rate only for defence-dominated genotypes that were not infected with nematodes. Elevated CO2 increased the number of nematode-induced galls on defence-dominated genotypes but not on wild-types or defence-recessive genotypes roots. Our results suggest that CO2 enrichment may not only increase plant C : N ratio but can disrupt the allocation of plant resources between growth and defence in some genetically modified plants and thereby reduce their resistance to nematodes.

Sympathetic nervous system contributes to orthodontic tooth movement by central neural regulation from hypothalamus.

Orthodontic tooth movement (OTM) is a specific treatment of malocclusion, whose regulation mechanism is still not clear. This study aimed to reveal the relationship between the sympathetic nervous system (SNS) and OTM through the construction of an OTM rat model through the utilization of orthodontic nickeltitanium coiled springs. The results indicated that the stimulation of SNS by dopamine significantly promote the OTM process represented by the much larger distance between the first and second molar compared with mere exertion of orthodontic force. Superior cervical ganglionectomy (SCGx) can alleviate this promotion effect, further proving the role of SNS in the process of OTM. Subsequently, the ability of orthodontic force to stimulate the center of the SNS was visualized by the tyrosin hydroxylase (TH) staining of neurons in ventromedial hypothalamic nucleus (VMH) and arcuate nucleus (ARC) of the hypothalamus, as well as the up-regulated expression of norepinephrine in local alveolar bone. Moreover, we also elucidated that the stimulation of SNS can promote osteoclast differentiation in periodontal ligament cells (PDLCs) and bone marrow-derived cells (BMCs) through regulation of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) system, thus promoting the OTM process. In conclusion, this study provided the first evidence for the involvement of the hypothalamus in the promotion effect of SNS on OTM. This work could provide a novel theoretical and experimental basis for further understanding of the molecular mechanism of OTM.

P53 Plays an Important Role in the Early Stage of Autologous Heterotopic Transplantation of Ovaries into the Backs of Mice.

BACKGROUND: Subcutaneous ovarian transplantation has recently begun receiving increased attention. Fourteen days after transplantation is used as an important time point for assessing the recovery of ovarian function. The goal of this study is to determine the expression of apoptotic genes in the ovary at this time. METHODS: This study investigated follicle development and the expression of 3 apoptosis genes (Bax, Bcl2, and P53) after mouse ovaries were transplanted. Seven-week-old mouse ovaries were autologously transplanted into back muscle. The ovaries were harvested on day 14, morphology was observed by hematoxylin and eosin staining, and the distribution of 3 proteins was observed by immunohistochemistry. TUNEL staining showed where apoptosis occurred in the ovary. Finally, RT-PCR/Western blotting was used to analyze the differential expression of mRNA/proteins between the transplantation group and the control group. RESULTS: The results revealed follicles at different stages at the edge of the grafts. In immunohistochemical experiments, BAX, BCL2, and P53 were found to be extensively expressed in the transplant group and the control group. P53 was strongly expressed in the medulla of transplanted ovaries. Bax was strongly expressed in the antral follicles of both groups. The results were consistent with the results of the TUNEL experiments. Three genes (Bax, Bcl2, and P53) were downregulated in the transplanted groups. The results showed that significant differences were detected in Bax and P53 mRNA expression levels between the transplanted groups and the control group (P < .01). Bcl2 expression was not significantly different, but the Bax/Bcl2 ratio increased. The results of the protein experiments were the same. CONCLUSION: P53 may downregulate Bax in the early stage of transplantation. Follicle growth and atresia were regulated through modulation of Bcl2- and Bax-mediated apoptotic pathways in heterotopic ovarian transplantation.

Comparative study of assisted reproductive outcomes between young patients with occult premature ovarian insufficiency and advanced-age patients.

OBJECTIVE: The purpose of this study was to compare the pregnancy outcomes among young patients with occult premature ovarian insufficiency (OPOI), advanced-age patients with diminished ovarian reserve (DOR), and advanced-age patients with normal ovarian reserve. METHODS: We retrospectively reviewed 324 women who underwent their first cycles of in vitro fertilization/intracytoplasmic sperm injection. The women were divided into the following groups: young women with OPOI, advanced-age women with DOR, and advanced-age women with normal ovarian reserve. The outcomes were compared among the different groups. RESULTS: The rates of live birth and embryo implantation in the young OPOI group were significantly higher than in the advanced-age DOR group, but comparable to those in the advanced-age normal ovarian reserve group. Moreover, the abortion rate was significantly lower in young OPOI patients compared with advanced-age patients with or without DOR. CONCLUSION: Higher embryo implantation and live birth rates and a lower abortion rate can be achieved in young patients with OPOI compared with older patients. The better outcomes in advanced-age patients with normal ovarian reserve compared with DOR may be related to egg quantity rather than quality.

A Systematic Study on Reproductive Endocrine Function Recovery From Subcutaneous Ovarian Autotransplantation in Mice After 2 Weeks.

BACKGROUND: Heterotopic ovarian transplantation can not only restore the reproductive and endocrine function of animals but can also be studied with a specialized animal model. The aim of the study was to determine whether the reproductive endocrine function of the subcutaneously transplanted ovary was restored after 2 weeks. METHODS: The ovaries of 7-week-old mice were autologously transplanted into the back muscle. Fourteen days later, the ovarian structure was examined by hematoxylin and eosin staining. We continuously observed vaginal smears for changes in the estrous cycle. Estrogen and androgen concentrations were detected on the 14th day. The oocytes were collected and then used for in vitro maturation (IVM) and in vitro fertilization (IVF). RESULTS: The cyclical estrous cycle changes were similar to those of the control group. There were no differences in the serum androgen and estrogen levels between the graft and control groups. The oocytes were able to develop into blastocysts after IVM and IVF. These results indicated that ovarian endocrine and reproductive function were restored within 2 weeks. CONCLUSION: Our studies have shown that this ovarian heterotopic autotransplantation technique is able to restore steroidogenic and gametogenic functions at day 14 after transplantation. So far, the 14th day after transplantation is a landmark during the recovery from autologous heterotopic ovarian transplantation in the back of the mouse. This time point is the appropriate window to study heterotopic ovarian transplantation in mice.

Gentianella macrosperma, a new species of Gentianella (Gentianaceae) from Xinjiang, China.

Gentianella macrosperma Ma ex H.F. Cao, J.D. Ya & Q.R. Zhang, a new species of Gentianaceae from Xinjiang, Northwest China is described and illustrated. This new species is unique in having equal length of corolla lobe and corolla tube, nectaries located at the throat of the corolla tube and large seeds up to 1.6 mm in diameter. In addition, an updated identification key to the Chinese species of Gentianella is provided.

Combination of Virtual Screening Protocol by in Silico toward the Discovery of Novel 4-Hydroxyphenylpyruvate Dioxygenase Inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is a potent new bleaching herbicide target. Therefore, in silico structure-based virtual screening was performed in order to speed up the identification of promising HPPD inhibitors. In this study, an integrated virtual screening protocol by combining 3D-pharmacophore model, molecular docking and molecular dynamics (MD) simulation was established to find novel HPPD inhibitors from four commercial databases. 3D-pharmacophore Hypo1 model was applied to efficiently narrow potential hits. The hit compounds were subsequently submitted to molecular docking studies, showing four compounds as potent inhibitor with the mechanism of the Fe(II) coordination and interaction with Phe360, Phe403, and Phe398. MD result demonstrated that nonpolar term of compound 3881 made great contributions to binding affinities. It showed an IC50 being 2.49 µM against AtHPPD in vitro. The results provided useful information for developing novel HPPD inhibitors, leading to further understanding of the interaction mechanism of HPPD inhibitors.

New Research for Quinazoline-2,4-diones as HPPD Inhibitors Based on 2D-MLR and 3D-QSAR Models.

AIM AND OBJECTIVE: 4-Hydroxyphenylpyruvate dioxygenase (HPPD), converting phydroxyphenylpyruvate (HPPA) to homogentisate (HGA), is an important target for treating type I tyrosinemia and synthesizing novel herbicides due to its significant role in tyrosine catabolism. Hence, it is imperative to design novel HPPD inhibitors that can block HPPA-HGA conversion, which leads to the deficiency in isoprenoid redox cofactors such as plastoquinone and tocopherol, and finally caused growth inhibition. This study was undertaken to investigate structural requirements for their HPPD inhibition with better biological activity. MATERIALS AND METHODS: Based on the structure-activity relationships, a series of quinolinone-2,4- diones derivatives were studied using combined of 2D multiple linear regression (2D-MLR) and 3D quantitative structure-activity relationship (3D-QSAR). Firstly, genetic algorithm (GA) was applied and descriptors generated in DRAGON 5.5 software were used for building 2D-MLR models in the QSARINGS. Then CoMFA and CoMSIA models were performed by using alignment of the common framework and the pharmacophore model. The obtained models were validated through internal and external validation to verify predictive abilities. Especially, the CoMFA and CoMSIA contour maps were used to show vital structural characteristics related to HPPD inhibitors activities. RESULTS: The 2D-MLR liner equation and corresponding parameters were listed as follows: pKi = -38.2034Me+22.4078GATS2m-1.4265EEig15r-2.1849Hy+32.9158 ntr=28, npred=6, R2=0.863, Q2LOO=0.787, Q2LMO=0.607, Q2F1=0.780, Q2F2=0.780, Q2F3=0.860, CCCpred=0.920. RMSEtr=0.253, RMSEpred=0.555, F=36.289 The steric contours graph indicated that small and negative electrostatic substitutions at R1 and R2 regions were favorable for the better activity, and hydrogen-bond donors at this region would also increase the activity. Positive electrostatic and bulky substitutions in the R3 position would enhance the activity. The analysis of these models suggested that the steric factor of R4 position was crucial for activity of quinazoline-2,4-diones HPPD inhibitors, bulky substitutions might improve the bioactivity of these inhibitors greatly, meanwhile, hydrogen-bond acceptor groups in this position were required for higher activity. CONCLUSION: In this study, a combined 2D-MLR, CoMFA and CoMSIA models demonstrated satisfying results through internal and external validation, especially good predictive abilities and the CoMFA and CoMSIA contour maps showed vital structural characteristics related to HPPD inhibitors activities.

Cadherin-11 modulates cell morphology and collagen synthesis in periodontal ligament cells under mechanical stress.

OBJECTIVE: To examine the role of cadherin-11, an integral membrane adhesion molecule, in periodontal ligament cells (PDLCs) under mechanical stimulation. MATERIALS AND METHODS: Human PDLCs were cultured and subjected to mechanical stress. Cadherin-11 expression and cell morphology of PDLCs were investigated via immunofluorescence staining. The mRNA and protein expressions of cadherin-11 and type I collagen (Col-I) of PDLCs were evaluated by quantitative real-time polymerase chain reaction and Western blot, respectively. Small interfering RNA was used to knock down cadherin-11 expression in PDLCs. The collagen matrix of PDLCs was examined using toluidine blue staining. RESULTS: Cadherin-11 was expressed in PDLCs. Mechanical stress suppressed cadherin-11 expression in PDLCs with prolonged force treatment time and increased force intensity, accompanied by suppressed ß-catenin expression. Simultaneously, mechanical stress altered cell morphology and repressed Col-I expression in a time- and dose-dependent manner in PDLCs. Moreover, knockdown of cadherin-11 with suppressed ß-catenin expression resulted in altered PDLC morphology and repressed collagen expression, which were consistent with the changes observed under mechanical stress. CONCLUSIONS: Results of this study suggest that cadherin-11 is expressed in PDLCs and modulates PDLC morphology and collagen synthesis in response to mechanical stress, which may play an important role in the homeostasis and remodeling of the PDL under mechanical stimulation.

Cascade effects of crop species richness on the diversity of pest insects and their natural enemies.

Understanding how plant species richness influences the diversity of herbivorous and predatory/parasitic arthropods is central to community ecology. We explore the effects of crop species richness on the diversity of pest insects and their natural enemies. Using data from a four-year experiment with five levels of crop species richness, we found that crop species richness significantly affected the pest species richness, but there were no significant effects on richness of the pests' natural enemies. In contrast, the species richness of pest insects significantly affected their natural enemies. These findings suggest a cascade effect where trophic interactions are strong between adjacent trophic levels, while the interactions between connected but nonadjacent trophic levels are weakened by the intermediate trophic level. High crop species richness resulted in a more stable arthropod community compared with communities in monoculture crops. Our results highlight the complicated cross-trophic interactions and the crucial role of crop diversity in the food webs of agro-ecosystems.

Elevated CO2 influences nematode-induced defense responses of tomato genotypes differing in the JA pathway.

Rising atmospheric CO(2) concentrations can affect the induced defense of plants against chewing herbivores but little is known about whether elevated CO(2) can change the induced defense of plants against parasitic nematodes. This study examined the interactions between the root-knot nematode Meloidogyne incognita and three isogenic tomato (Lycopersicon esculentum) genotypes grown under ambient (390 ppm) and elevated (750 ppm) CO(2) in growth chambers. In a previous study with open-top chambers in the field, we reported that elevated CO(2) increased the number of nematode-induced root galls in a JA-defense-dominated genotype but not in a wild-type or JA-defense-recessive genotype. In the current study, we tested the hypothesis that elevated CO(2) will favor the salicylic acid (SA)-pathway defense but repress the jasmonic acid (JA)-pathway defense of plants against plant-parasitic nematodes. Our data showed that elevated CO(2) reduced the JA-pathway defense against M. incognita in the wild-type and in a genotype in which defense is dominated by the JA pathway (a JA-defense-dominated genotype) but up-regulated the SA-pathway defense in the wild type and in a JA-defense-recessive genotype (jasmonate-deficient mutant). Our results suggest that, in terms of defense genes, secondary metabolites, and volatile organic compounds, induced defense of nematode-infected plants could be affected by elevated CO(2), and that CO(2)-induced changes of plant resistance may lead to genotype-specific responses of plants to nematodes under elevated CO(2). The changes in resistance against nematodes, however, were small relative to those reported for chewing insects.