Novel STAT3 oligonucleotide compounds suppress tumor growth and overcome the acquired resistance to sorafenib in hepatocellular carcinoma.

Signal transducer and activator of transcription 3 (STAT3) plays an important role in the occurrence and progression of tumors, leading to resistance and poor prognosis. Activation of STAT3 signaling is frequently detected in hepatocellular carcinoma (HCC), but potent and less toxic STAT3 inhibitors have not been discovered. Here, based on antisense technology, we designed a series of stabilized modified antisense oligonucleotides targeting STAT3 mRNA (STAT3 ASOs). Treatment with STAT3 ASOs decreased the STAT3 mRNA and protein levels in HCC cells. STAT3 ASOs significantly inhibited the proliferation, survival, migration, and invasion of cancer cells by specifically perturbing STAT3 signaling. Treatment with STAT3 ASOs decreased the tumor burden in an HCC xenograft model. Moreover, aberrant STAT3 signaling activation is one of multiple signaling pathways involved in sorafenib resistance in HCC. STAT3 ASOs effectively sensitized resistant HCC cell lines to sorafenib in vitro and improved the inhibitory potency of sorafenib in a resistant HCC xenograft model. The developed STAT3 ASOs enrich the tools capable of targeting STAT3 and modulating STAT3 activity, serve as a promising strategy for treating HCC and other STAT3-addicted tumors, and alleviate the acquired resistance to sorafenib in HCC patients. A series of novel STAT3 antisense oligonucleotide were designed and showed potent anti-cancer efficacy in hepatocellular carcinoma in vitro and in vivo by targeting STAT3 signaling. Moreover, the selected STAT3 ASOs enhance sorafenib sensitivity in resistant cell model and xenograft model.

The novel STAT3 inhibitor WZ-2-033 causes regression of human triple-negative breast cancer and gastric cancer xenografts.

Hyperactive signal transducer and activator of transcription 3 (STAT3) signaling is frequently detected in human triple-negative breast cancer (TNBC) and gastric cancer, leading to uncontrolled tumor growth, resistance to chemotherapy, and poor prognosis. Thus, inhibition of STAT3 signaling is a promising therapeutic approach for both TNBC and gastric cancer, which have high incidences and mortality and limited effective therapeutic approaches. Here, we report a small molecule, WZ-2-033, capable of inhibiting STAT3 activation and dimerization and STAT3-related malignant transformation. We present in vitro evidence from surface plasmon resonance analysis that WZ-2-033 interacts with the STAT3 protein and from confocal imaging that WZ-2-033 disrupts HA-STAT3 and Flag-STAT3 dimerization in intact cells. WZ-2-033 suppresses STAT3-DNA-binding activity but has no effect on STAT5-DNA binding. WZ-2-033 inhibits the phosphorylation and nuclear accumulation of pY705-STAT3 and consequently suppresses STAT3-dependent transcriptional activity and the expression of STAT3 downstream genes. Moreover, WZ-2-033 significantly inhibited the proliferation, colony survival, migration, and invasion of TNBC cells and gastric cancer cells with aberrant STAT3 activation. Furthermore, administration of WZ-2-033 in vivo induced a significant antitumor response in mouse models of TNBC and gastric cancer that correlated with the inhibition of constitutively active STAT3 and the suppression of known STAT3 downstream genes. Thus, our study provides a novel STAT3 inhibitor with significant antitumor activity in human TNBC and gastric cancer harboring persistently active STAT3.

Reliability and validity of the Chinese version of the HIV Treatment Adherence Self-Efficacy Scale in mainland China.

The aim of this study was to translate the HIV Treatment Adherence Self-Efficacy Scale (HIV-ASES) and evaluate its reliability and validity in people living with HIV (PLWHIV) in mainland China. The original HIV-ASES was translated from English into Chinese and adapted for cultural context according to cross-cultural adaptation guidelines. A cross-sectional survey investigating 1742 PLWHIV receiving antiretroviral treatment was conducted. Exploratory factor analysis with varimax rotation confirmed the presence of two factors with an accumulated contribution rate of 58.357%. Furthermore, confirmatory factor analysis revealed the model's goodness-of-fit index. The comparative fit index was greater than 0.9 and the overall efficacy of the model was satisfactory. The Cronbach α coefficient of the questionnaire was 0.876 (95% CI: 0.868-0.885), and the correlation coefficient of each item and the total was 0.536-0.660 ( P < 0.01). The Chinese version of the HIV-ASES has high reliability and validity; however, the individual item requires some adjustment.

[Correlation analysis of G870A CCND1 gene polymorphism with digestive system tumors].

OBJECTIVE: To study the correlation of G870A CCND1 gene polymorphism and digestive system tumors. METHODS: From August 2010 to August 2014, 164 digestive system cancer patients (including 82 patients with gastric cancer and 82 with colorectal cancer) and 82 healthy subjects (control group) were examined with PCR-restriction fragment length polymorphism (PCR-RFLP). The distribution of CCND1 gene G870A frequency in the 3 groups and its association with tumor staging and grading were analyzed. RESULTS: The frequencies of the GG, GA and AA genotypes in G870A CCND1 gene loci in patients with gastric cancer and colorectal cancer differed significantly from those in the control group (P<0.05). G870A CCND1 gene polymorphism was closely associated with an increased risk of digestive system tumors (P<0.05). The GA and AA genotypes were associated with a significantly higher risk of digestive system cancer risk than the GG genotype (P<0.05), and their frequencies were significantly higher in patients with tumors of higher pathological grade and in those in advanced tumor stages (P<0.05). CONCLUSION: G870A CCND1 gene polymorphism is associated with the risk of digestive system tumors. The allele A is associated with an increased risk of digestive system tumors and correlated with the tumor differentiation and staging of the tumor.

Possibly propylthiouracil-induced antineutrophilic cytoplasmic antibody-associated vasculitis manifested as blood coagulation disorders: A case report.

BACKGROUND: Propylthiouracil is the most common drug used to treat hyperthyroidism. However, this drug could cause a severe disease, antineutrophilic cytoplasmic antibody-associated vasculitis (AAV), which was usually misdiagnosed. METHODS: We reported a 60-year-old woman of propylthiouracil-induced AAV manifested as blood coagulation disorders. The patient was admitted because of hyperthyroidism and leukopenia. At the time of hospitalization, she suffered from dry cough, erythema and knee joints ache, and gradually became febrile. And then BP decreased and PLT was reduced with coagulation disorders. ANCA: c-ANCA positive (1:100), p-ANCA positive (1:320), MPO-IgG positive, PR3-IgG positive, GBM-IgG negative. Erythrocyte sedimentation rate and C-reactive protein increased markedly. Chest high-resolution computed tomography (HRCT) showed that scattered spots, patch and ground-glass opacity. RESULTS: Finally, we made a terminal diagnosis of PTU-induced AAV possibly. After drug withdrawal and use of steroid, the patient recovered well and then accepted RAI therapy. As the patient was given imipenem-cilastatin before the reduction of PLT and coagulation disorders, we considered that the hematologic disorders might be caused by antibiotics or a clinical presentation of the vasculitis itself. CONCLUSION: Drug-induced vasculitis is relatively good prognosis, but early diagnosis and timely withdrawal of associated drugs are the key to the treatment.

[Study on the Application of Raman Spectroscopy to the Research on Natural Cellulose Structure].

As the skeleton substances of lignocellulosic biomass cell wall and the precursor of biofuels production, the research on cellulose structure, an important natural biomarcromolecules, attracts great attention. Considering its in situ features and higher resolution, Raman spectroscopy has been used to investigate the structure of cellulose molecular chain and cellulose aggregation structure at multi-scale. In this paper, the configurations and corresponding parameters of two types of Raman spectroscopy (Dispersive Raman and FT-Raman) were compared. Subsequently, the utilization of Raman spectroscopy in cellulose micro-distribution, cellulose enzyme hydrolysis, cellulose chain orientation and deformation, cellulose crystallinity and polymorphic transformation was discussed in detail. Given the existing deficiencies of the Raman spectroscopy when used to investigate the natural cellulose, some suggestions were proposed in order to promote the application of Raman spectroscopy to the research of natural macromolecular.

[Rapidly Detection for Moso Bamboo Density under Different Moisture ConditionBased on X-CT Technology].

Density, which is closely relate with many physical and mechanical properties of bamboo, is one of the important indicators of bamboo material properties. Moreover, because of existing different moisture gradients in bamboo, the measured results of the density are different. Based on X-ray computed tomography (X-CT) technology, the divergent degree of the CT values of 7 different aged Moso bamboo was compared under oven-dried, air-dried and water-saturated conditions. Except for the 4-year-old and 10-year-old Moso bamboo, the CT values of other aged bamboos have minor differences with each other; the models for the measured CT values and the corresponding densities of Moso bamboo were respectively fitted under oven-dried, air-dried and water-saturated conditions. Meanwhile, the model was also fitted under different moisture gradients, which was composed by the measured CT values and the corresponding densities of Moso bamboo. Then the relations between the CT values andthe densitiesof 7 different aged Moso bamboo were systematically analyzed under single moisture content and three moisture gradients;the CT values were fitted under oven-dried condition, of which the radial positions are relative to the outer of Moso bamboo. According to the relation between the CT value and the density, the fitting curves explain the reasons for the radial density variations of 7 different aged Moso bamboo. Results show that the relations, which are fitted by the measured densities and the corresponding CT values of 7 different aged Moso bamboo under oven-dried, air-dried and water-saturated conditions, are good linear and the slopes of those models are approximate; the relation of the densities with the CT values for Moso bamboo is linear under different moisture gradients, moreover, which is rarely affected by moisture. The regression equation is: D=0.001 H+1.003 2, R2=0.968 3(D is the density, H is the CT value) and the determination coefficient of the validation model is: R2=0.974 3; there is no obvious variation between the densities of the inner and the outer, but not in middle part to 7 different aged Moso bamboo under oven-dried condition. To realize rapid detection on the densities of Moso bamboo under different moisture content, these results provide technical support and data reference. At the same time, X-ray computed tomography (X-CT) technology also puts forward a new feasible way for the further studies of bamboo material properties and structure.

[Study on the Crystal Structure of Cellulose in Bamboo with Synchrotron Radiation Wide Angle X-Ray Scattering].

The crystal structure of cellulose will directly affect the properties of bamboo fiber -reinforced composite, but the unit cell of native cellulose in bamboo has never been investigated. The most accepted model for the structure of native cellulose is Meyer-Misch model which provides a reference to understand the unit cell of native cellulose in bamboo. The native cellulose consists of two different crystal structures (Ⅰ(α) and Ⅰ(ß)) which exist in different plants with different proportions. Because of this situation, the crystal structure of bamboo cellulose should have a unique model. The moso bamboo (Phyllostachys edulis (Carr. ) H. de Lehaie)was selected. The crystal structure of cellulose of bamboo was investigated with two dimensional synchrotron radiation wide angle X-ray scattering (SR-WAXS). The values of the interplanar spacings of each peak were obtained from SR-WAXS patterns, and then crystal structure parameters were calculated according to monoclinic crystal system. The results show that the fibre axis of a bamboo cellulose unit cell with a monoclinic unit cell of a=8.35 Å, b (fiber axis)=10.38 Å, c=8.02 Å, ß=84.99°. This model has a two antiparallel arrangement for the chains in unit cell, with four glucose residues. Thus, the model may be used to provide a theoretical basis for high value-added bamboo fiber -reinforced composite.

[Study on Non-Destructive Testing of Guqin Interior Structure Based on Computed Tomography].

The wood property and production process affect quality of Guqin. At the same time, Guqin shape with cavity layout relations to the improvement of Guqin technology and inheritance, so it's very important to get the internal cavity characteristics and parameters on the condition of non-destructive the structure of Guqin. The image of interior structure in Guqin was investigated by overall scanning based on non-destructive testing technology of computed tomography, which texture of faceplate, connection method between faceplate and soleplate and interior defects were studied. The three-dimensional reconstruction of Guqin cavity was achieved through Mimics software of surface rendering method and put the two-dimensional CT tomography images convert into three-dimensional, which more complete show interior structural form in Guqin, and finally the parameter of cavity dimensions was obtained. Experimental research shows that there is significant difference in Guqin interior structure between Zhong-ni and Luo-xia type, in which the fluctuation of the interior surfacein Zhong-ni type's is larger than that in Luo-xia type; the interior volume of Zhong-ni typeis less than that of Luo-xia type, especially in Guqin neck. The accurate internal information of Guqin obtained through the computed tomography (CT) technology will provide technical support for the Guqin manufacture craft and the quality examination, as well as provide the reference in the aspect of non-destructive testing for other traditional precious internal structure research.

Isolation of antifungal compound from Paeonia suffruticosa and its antifungal mechanism.

OBJECTIVE: To isolate antifungal compound from Paeonia suffruticosa, and to find the antifungal mechanisms by observing the ultrastructural modifications of yeasts in growth phase produced by 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG). METHODS: Peony (Paeonia suffruticosa) root bark (PRB) was separated by solvent extraction and purified by high performance liquid chromatography (HPLC) method using analytical and preparative reversed phase C18 column on the basis of bio-assay method. In order to investigate the antifungal mechanism of PGG, Yeasts were submitted to different concentrations [3 × minimum inhibition concentration (MIC), 0.3 × MIC] for 1 h under constant stirring at 30 °C, and transmission electron microscopy was performed. RESULTS: Based on the antifungal activity of PRB on Candida glabrata CBS138, the antifungal compound were isolated in ethyl acetate layer of PRB and identified as PGG by mass spectrometry, 1H nuclear magnetic resonance (NMR) analyses, with molecular weight of 940 and molecular formular as C41H32O26. Transmission electron microscopy showed that PGG degraded the cell wall envelope. CONCLUSION: The results suggest that PGG may be responsible for the antifungal activity of PRB by disrupting the structure of cell wall directly.

[Variation of microfibril angle in Dendrocalamus farinosus analyzed based on X-ray diffraction spectrum and its effect on tensile properties].

X-ray diffraction technology was used to rapidly predict variation in microfibril angle (MFA) in Dendrocalamus fari- X-ray diffraction technology was used to rapidly predict variation in microfibril angle (MFA) in Dendrocalamus farinosus. The results show that there is little variation in MFA with bamboo age from 2a to 5e, and MFA of 3a is at the maximum with the value of 8.521 degrees. The average value of MFA of 2a or 3a is greater than 4a or 5a with absolute differences less than 0.10 degrees. MFA of base, middle and upper position respectively are 8.499 degrees, 8.497 degrees and 8.483 degrees with coefficient of variation about 5%. There is an increasing tendency from the periphery to the inner of bamboo culms. Variance analysis indicates that MFA is highly sensitive to radial position, but insensitive to bamboo age and longitudinal position. The correlation coefficient of longitudinal strength and modulus of elasticity (MOE) is 0.57. MFA was responsible for 35% and 43% of the variation found in longitudinal strength and MOE respectively, which means MFA has a certain extent effect on mechanical properties.

[Research on density detection in Dendrocalamus farinosus based on computer tomography].

Density is one of the important physical indicators of bamboo, associated with its many physical and mechanical properties. The temporal and spatial variation of density in 2-5-year-old Dendrocalamus farinosus were measured using computed tomography (CT) technology. Scanning parameters were obtained through orthogonal design. The relationship of air-dry density (Y) and the corresponding CT values (X) was established and verified through regression analysis, which presents an approximate linear relationship between them. The linear equation is Y=0.001X+1.148. The radial and longitudinal variation of density was determined by the regression model. This study provides a new method to measure bamboo density efficiently and accurately, and also put forward a new thought to further study structure and characteristics of bamboo.

Chemical constituents from the leaves of Aglaia odorata.

A new dammarane triterpene, 3-acetoxy aglinin C (1), and a new aglain, 10-oxo-aglaxiflorin D (2), along with five known compounds, 3-7, were isolated from the leaves of Aglaia odorata using chromatographic methods. The structures of 1 and 2 were determined on the basis of spectroscopic analyses. Bioactivities of 1-7 against AGZY 83-a (human lung cancer cell line) and SMMC-7721 (human liver cancer cell line) cells were determined.

[Investigation of characteristic microstructures of adhesive interface in wood/bamboo composite material by synchrotron radiation X-ray phase contrast microscopy].

Third-generation synchrotron radiation X-ray phase-contrast microscopy(XPCM)can be used for obtaining image with edge enhancement, and achieve the high contrast imaging of low-Z materials with the spatial coherence peculiarity of X-rays. In the present paper, the characteristic microstructures of adhesive at the interface and their penetration in wood/bamboo composite material were investigated systematically by XPCM at Shanghai Synchrotron Radiation Facility (SSRF). And the effect of several processing techniques was analyzed for the adhesive penetration in wood/bamboo materials. The results show that the synchrotron radiation XPCM is expected to be one of the important precision detection methods for wood-based panels.

[Measuring the density of wood and bamboo using computed tomography].

CT is widespread non-destructive detection technique for wood materials, and the density measurement is a key role during this application. In the present report, the use of CT for air-dry density measurement of wood and bamboo is described. The authors found that there were marked linear correlations between air-dry density (0.303-1.061 g x cm(-3)) of 24 kinds of woods and their respective CT value, as well as 25 kinds of lignin materials (including 24 kinds of woods and 1 kind of bamboo) and the CT value, both with correlation coefficient of 0.99, which belonged to the CT technological breakthrough for wood quantitative detection These research results show that CT is an appropriate way to measure density for wood and bamboo, and would provide technical support for CT used in the field of wood science research and wood processing.

Treatment adherence among sputum smear-positive pulmonary tuberculosis patients in mountainous areas in China.

BACKGROUND: We carried out an investigation in five provinces in China to assess treatment adherence and identify factors associated with insufficient treatment adherence in tuberculosis (TB) patients in mountainous, rural areas of China. METHODS: In each of the five provinces, all counties with > 80% mountainous area were stratified into three groups according to their gross domestic product. In each stratum, one county was randomly sampled. Study subjects were sampled from all smear positive TB cases registered in 2007 in the target counties. TB patients, village doctors, county doctors and directors of the TB prevention and control institutes were interviewed. Insufficient medication adherence was defined as taking less than 90% of anti-TB drug doses prescribed. Insufficient re-examination adherence was defined as having less than the recommended three sputum smear examinations during the treatment course. RESULTS: A minority of patients took drugs under direct observation: on average 29% during the intensive phase of treatment. In total, 524 TB patients were included, of whom 49 (9.4%) took less than 90% of all doses prescribed and 92 (17.6%) did not have all sputum smear examinations, with substantial variations between the provinces. In multivariable analysis, no direct observation of treatment during the intensive phase and the presence of adverse events were associated both with insufficient medication adherence and insufficient re-examination adherence. Overall, 79% of patients were adherent both to treatment and re-examinations. CONCLUSIONS: In these remote and poor areas of China, the TB control program is not fully functioning according to the guidelines. The majority of patients are not treated under direct observation, while direct observation by health care staff was associated with better adherence, both to drug therapy and re-examinations. Insufficient adherence increases the risk of unsuccessful treatment outcomes and development of drug resistance. Measures should be taken urgently in these areas to strengthen implementation of the international Stop TB strategy.

Anticancer activity of diterpenoids from Amoora ouangliensis and Amoora stellato-squamosa.

A new ent-halimane-type diterpene, named 5(10),14-ent-halimadien-3beta,13S-diol (1), was isolated from the bark of Amoora ouangliensis and its chemical structure determined on the basis of spectroscopic analysis. Additionally, ten other diterpenoids were obtained from A. ouangliensis and A. stellato-squamosa. The bioactive experiments of all compounds against AGZY 83-a (human lung cancer cells) and SMMC-7721 (human liver cancer cells) cells were documented.

[Determination of lignin distribution during ageing of bamboo culms (Phyllostachys pubescens) with visible-light spectrophotometry].

The lignin distribution in different anatomical regions of developing moso bamboo Phyllostachys pubescens f. lutea Wen was investigated by means of optical microscope and visible-light microspectrophotometry coupled with the Wiesner and Maule reaction. The lignin is widely distributed in different tissues, in which there is a difference in lignin content between different ages, tissues and anatomical regions. Guaiacyl lignin and Syringyl lignin unit can be found in cell wall of fibre, parenchyma and vessel. Lignin content of secondary wall, cell corner and compound middle lamellae of fibre increased gradually within 12 months, then almost remained in the same level or decreased slowly in the culms with an age from 12 to 78 months. The lignification rate in secondary wall, cell corner and compound middle lamellae of fibre changed with age until they reached a relative steady value. There is no regular variation in lignin content with different radial location of culms and different location in fibre strands within one age. The secondary wall, compound middle lamellae of parenchyma and vessel secondary wall lignified rapidly within 12 months, and then changed slowly.

[The effects of glucocorticoid on expression of cannabinoid-1 receptors in osteoclasts from tibial proximal metaphysis of rats].

OBJECTIVE: To explore the molecular mechanism of glucocorticoid (GC)-induced osteoporosis (GIOP). METHODS: Thirty-two female SD rats after matching body weight were divided randomly into three groups: baseline group (n = 10), control group (n = 11) and GC-treated group (n = 11). The administration time was 9 weeks. Bone mineral density (BMD) was measured with dual energy X-ray absorptiometry. A high resolution micro-CT was used to quantify the densitometric and microarchitectural properties of trabeculae in the proximal metaphysis of right tibia. In situ hybridization histochemistry and immunohistochemistry were used to detect the expression of cannabinoid type 1 receptor (CB1R) in the proximal metaphysis of left tibia. RESULTS: At the end of the experiment, whole-body BMD in vivo in the control group [(0.156 +/- 0.008) g/cm(2)] was higher than that in the baseline group [(0.147 +/- 0.006) g/cm(2)], while the whole-body BMD in vivo [(0.147 +/- 0.006) g/cm(2)] and total BMD in vitro at femurs in the GC-treated group [(0.220 +/- 0.011) g/cm(2)] was lower than those in the control group [(0.240 +/- 0.024) g/cm(2)]. Compared with the baseline group and control group, there was a remarkable decrease in the volumetric BMD, tissue BMD, trabecular number and trabecular connectivity (P < 0.05) in the GC-treated group, while there was a significant increase in trabecular separation (P < 0.05) and trabecular thickness also increased in the proximal metaphysis of tibiae in the GC-treated group. The expression level of CB1R mRNA and protein in osteoclasts in the GC-treated group was markedly higher than that in the baseline group and control group (P < 0.05). There was a close correlation between the expression level of CB1R mRNA, protein in osteoclasts and some microarchitectural parameters in the proximal metaphysis in the GC-treated group (P < 0.05). CONCLUSIONS: The administration of GC is associated with a decrease in BMD and deterioration in microarchitecture of trabecular bone in rats tibiae. Glucocorticoid may up-regulate the CB1R expression level in osteoclasts and this may be a kind of molecular mechanism of GIOP.

[Dynamic effects of glucocorticoid on bone mineral density and microarchitecture: experiment with rats].

OBJECTIVE: To investigate the Dynamic effects of glucocorticoid (GC) on bone mineral density and microarchitecture time-related changes of trabecular bone in bone mineral density (BMD) and microarchitecture in glucocorticoid-treated rats. METHODS: Fifty-two 3.5-month-old female SD rats were randomly divided into 3 groups. Ten rats were killed at the beginning of experiment with their right tibiae taken out as the baseline group; 22 rats underwent subcutaneous injection of methylprednisolone once daily (GC-treated group), and the other 20 rats underwent subcutaneous injection of normal saline once daily as control group. One and 9 weeks after the beginning of experiment 11 and 10 rats from GCT Group and control group each were killed with their right tibiae taken out. High resolution micro-CT was used to identify the densitometric and microarchitectural properties of the trabecula in the proximal metaphysic of tibia. RESULTS: Compared with the control group the values of volumetric BMD (vBMD), tissue BMD (tBMD), bone volume fraction (BVF), trabecular number (Tb.N), degree of anisotropy (DA), and trabecular connectivity (Conn.D) in the trabecular bone at different time-points, of the GCT group all decreased; and the values in the ninth week were the lowest (all P < 0.05). The values of trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), and structure model index (SMI) at different time-points of the GCT group were higher than those of the control group. A time-related analysis within the GCT group showed there was a declination in BVF, Conn.D, Tb.N, and DA with administration time, but Tb.Th and Tb.Sp were increased significantly (all P < 0.05). The mean values of Tb.Th in the first week and the ninth week of GCT Group were (0.076 +/- 0.020) mm and (0.086 +/- 0.026) mm respectively, both higher than the baseline value [(0.067 +/- 0.014) mm] and the values of the control group in the first and ninth weeks [(0.075 +/- 0.022) mm and (0.072 +/- 0.009) mm respectively]. CONCLUSION: Administration of GC time dependently decreases the BMD and causes deterioration in microarchitecture of trabecular bone; and the remaining trabeculae seem thicken to increase their strength as compensation.