Distal tibiofibular syndesmosis fibular notch typing and its clinical significance based on CT / 解剖学报

Objective To investigate the morphological typing and clinical significance of the distal tibiofibular syndesmosis fibular notch based on CT images. Methods According to the inclusion and exclusion ceiteria‚ the imaging data of patients undergoing ankle joint CT examination were analyzed‚ and the inferior tibiofibular joint fibula notch was classified according to the morphological characteristics. The measurements included 8 distances. There were 123 males and 102 females‚ all of whom were Han nationality‚ aged 18-60 years old. Results Retrospectively analyzed the result of 225 patients from December 2013 to December 2022. The distal tibiofibular syndesmosis fibular notch was divided into four types according to morphological characteristics‚ C-shaped (50. 67%)‚ V-shaped (26. 67%)‚ flat-shaped (15. 11%) and L-shaped (7. 56%). The angle between the anterior and posterior facets of the flat shape (145. 56 ± 9. 25)° was the largest and the angle between the anterior and posterior facets of the L shape (125. 07 ± 13. 54)° was the smallest(P< 0. 05); the depth of the notch in the flat shape (3. 11 ± 0. 83) mm was the smallest and in the L shape (4. 47±1. 11) mm was the largest(P<0. 05);The posterior facet length (13. 06 ± 3. 56) mm and anterior tibiofibular gap (3. 83±1. 49) mm on left were larger than on the right side (P<0. 05); The posterior facet length (13. 36 ± 3. 46) mm‚ fibular notch depth (3. 93 ± 1. 10) mm and vertical distance of tibiofibular overlap (9. 10 ± 2. 55) mm larger in men than in women (P<0. 05). Conclusion In this study‚ the data related to the inferior tibiofibular syndesmosis notch were measured and divided into four types according to the shape. The flat inferior tibiofibular syndesmosis notch is more likely to have chronic ankle instability‚ and the fibula is more likely to move forward during anatomical reduction. The inferior tibiofibular syndesmosis of L-shaped and C-shaped notches is more prone to posterior displacement of fibula or poor rotation reduction during anatomical reduction.

The safe zone of distal fibula was determined based on the classification of lateral malleolus fossa.

BACKGROUND: Lateral malleolus fractures are very common, and the distal fibular geometry is complex. This study aimed to classify the lateral malleolus fossa (MF) into different types by characterizing the lateral MF imaging morphology and exploring the relationship between the lateral MF and internal fixation position after distal fibula fractures. METHODS: Anteroposterior CT reconstruction was performed on 248 subjects. After reconstruction, the deepest point of the lateral MF was located, and then, the cross-sectional shape of the lateral MF was observed and classified. RESULTS: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C (43.1%), type V (32.2%), and type Flat (24.7%). Type V (3.98 ± 0.82) was significantly longer than type C(2.83 ± 0.54) and type Flat (1.84 ± 0.42) in cd. Similarly, in ∠α, Type Flat(136.31 ± 9.63) was the largest, followed by type C (116.51 ± 8.79), and type V (89.31 ± 9.07) was the smallest. Other measurements were not found any significant differences between the above. CONCLUSION: According to the morphology of the CT cross section, the lateral MF was divided into three types: type C, type V and type Flat. Type V is most likely to be invaded when fixing the distal fibula. Screws less than 9 mm should be selected when fixing, and screws no more than 10 mm should be selected when there are type C and type Flat of MF.

Validation, inter-comparison, and usage recommendation of six latest VIIRS and MODIS aerosol products over the ocean and land on the global and regional scales.

MODIS and VIIRS aerosol products have been used extensively by the scientific community. Products in operation include MODIS Dark Target (DT), Deep Blue (DB), and Multi-Angle Implementation of Atmospheric Correction (MAIAC) and VIIRS DT, DB, and NOAA Environmental Data Record products. This study comprehensively validated and inter-compared aerosol optical depth (AOD) and Ångstrom exponent (AE) over land and the ocean of these six products (seven different algorithms) on regional and global scales using AErosol RObotic NETwork (AERONET) and Maritime Aerosol Network (MAN) observations. In particular, we used AERONET inversions to classify AOD and AE biases into different scenarios (depending on absorption and particle size) to obtain retrieval error characteristics. The spatial patterns of the products and their differences were also analyzed. Collectively, although six satellite AODs are in good agreement with ground observations, VIIRS DB (land and ocean) and MODIS MAIAC (land only) AODs show better validation metrics globally and better performance in 8/10 world regions. Therefore, they are more recommended for usage. Although land AE retrievals are not capable of quantitative application at both instantaneous and monthly scales, their spatial patterns show qualitative potential. Ocean AE shows a relatively high correlation coefficient with ground measurements (>0.75), meeting the fraction of expected accuracy (> 0.70). Error characteristic analyses emphasize the importance of aerosol particle size and absorption-scattering properties for land retrieval, indicating that improving the representation of aerosol types is necessary. This study is expected to facilitate the usage selection of operating VIIRS and MODIS products and their algorithm improvements.

Malignant peritoneal mesothelioma.

Malignant peritoneal mesothelioma (MPM) is a rare, life-threatening malignant tumor. We present a report of a rare case of a 67-year-old male patient with MPM and severe abdominal pain, bloating, and bloody ascites as manifestations. The diagnosis was confirmed by cytology of ascites aspiration fluid and further verified by laparoscopic exploratory biopsy. The characteristics of signs and clinical manifestations in this case are less common. As everyone knows, asbestos exposure is usually associated with pleural mesothelioma, but only 6%-10% of malignant mesothelioma cases originate from the peritoneum, which is far less than pleural mesothelioma. Generally, its non-specificity provides a huge challenge to medical professionals in its diagnosis, and this is also the main reason for delayed diagnosis. Patients should be vigilant, even though no clear risk factor is observed.

Beneficial effects of ginsenosides on diabetic nephropathy: A systematical review and meta-analysis of preclinical evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginseng is one of the most widely used herbs in the world for the treatment of various diseases, and ginsenoside is the representative bioactive component in ginseng. There have been many in vivo studies on ginsenoside for the treatment of diabetic nephropathy (DN), the most common diabetic microvascular complication and the main cause of diabetic morbidity and mortality. AIM OF THE STUDY: The purpose of this study is to evaluate the efficacy of ginsenosides on DN by preclinical evidence and meta-analysis. Meanwhile, the main possible action mechanisms of ginsenosides against DN were also summarized. MATERIALS AND METHODS: We systematically searched PubMed, WOS, Embase, Cochrane, WanFang, Cqvip, CNKI and CBM databases from January 1, 2000, to November 15, 2021, to evaluate the animal experiments of ginsenosides for the treatment of DN. Finally, 30 animal experiments were included. Twelve outcome measures, including renal function indicators (24-h urine protein, serum creatinine, urea nitrogen, creatinine clearance, uric acid, urinary albumin to creatinine ratio), oxidative stress biomarkers (GPX, MDA, SOD), inflammatory factors (IL-1, IL-6, TNF-α) were obtained by using RevMan 5.4 software for meta-analysis. RESULTS: The results showed that except for no significant difference in CCr, other indicators such as 24h UP, SCr, blood urea nitrogen, uric acid and UACR were significantly decreased. It showed that ginsenoside could improve renal function in diabetes. Meanwhile ginsenoside significantly up-regulated antioxidant enzymes SOD and GPX, down-regulated MDA and inflammatory factors IL-1, IL-6 and TNF-α, indicating that ginsenoside may have antioxidant and anti-inflammatory effects. CONCLUSION: Ginsenoside can protect against the renal failure in diabetes through anti-inflammation, anti-oxidation, anti-renal fibrosis, anti-apoptosis/pyroptosis, regulation of blood glucose/lipid metabolism, etc. Which provides preclinical evidence for the application of ginsenoside in the treatment of DN.

Retrieval of total and fine mode aerosol optical depth by an improved MODIS Dark Target algorithm.

Total and fine mode aerosol optical depth (AODT and AODF), as well as the fine mode fraction (FMF = AODF/AODT), are critical variables for climate change and atmospheric environment studies. The retrievals with high accuracy from satellite observations, particularly FMF and AODF over land, remain challenging. This study aims to improve the Moderate-resolution Imaging Spectro-radiometer (MODIS) land dark target (DT) algorithm for retrieving AODT, AODF, and FMF on a global scale. Based on the fact that the underestimated surface reflectance (SR) could overestimate the AODT and underestimate the aerosol size parameter in the DT algorithm, two robust schemes were developed to improve SR determination: the first (NEW1 DT) used the top of the atmosphere reflectance instead of SR at 2.12 µm; the second (NEW2 DT) used eleven-year MODIS data to establish a monthly spectral SR relationship model (2.12-0.47 and 2.12-0.65 µm) database at pixel-by-pixel scale. Then a novel lookup table approach based on the physical process was proposed to retrieve the AODF and FMF. The new MODIS AODT, FMF, and AODF were compared to AERosol RObotic NETwork (AERONET) retrievals. Results showed that the root mean square error (RMSE) was 0.096-0.103, 0.098-0.099, and 0.167-0.180 for the new AODTs, AODFs, and FMFs, respectively, which were better than that of the Collection 6.1 (C6.1) DT (0.117, 0.235, and 0.426) in the validation by global AERONET sites. From the validation results, NEW2 DT provided better AODT and coarse mode AOD retrievals, while NEW1 DT had better AODF and FMF performances. The spatial patterns of AODF, FMF, and AODC of the new DT algorithms were comparable to those of the Polarization and Directionality of the Earth's Reflectances aerosol product. Hence, the new algorithms have the potential to provide global AODT, FMF, and AODF products over land to the scientific community with high accuracy using long-term MODIS data.

Environmental factors modulate the diffuse fertilization effect on gross primary productivity across Chinese ecosystems.

Diffuse radiation allocated by cloud cover and aerosols can promote vegetation photosynthesis, which is known as the diffuse fertilization effect (DFE). As an important uncertain factor regulating the DFE, understanding the role of environmental conditions in the response of terrestrial ecosystems to diffuse radiation is vital for quantitative and intensive studies. By using a light use efficiency model and statistical methods with satellite data and ChinaFLUX observation data, the optimal environmental range of DFE was estimated, the indirect role of vapor pressure deficit (VPD) and air temperature (Ta) on DFE was explored, and the relative contribution of diffuse photosynthetically active radiation (PARdif) on gross primary productivity (GPP) was analyzed across Chinese ecosystems under different sky conditions. The results showed that the DFE increased with leaf area index (LAI), but distributed a unimodal curve along with VPD and Ta, both of which had an optimum range that was lower in the forest (or cropland) and higher in the grass (or desert) ecosystem. When considering the co-effect of VPD and Ta, the strongest positive effect of DFE was found at 0-5 h Pa and 20-25 °C. Based on path analysis, PARdif promoted GPP and served as the main controlling factor in forest ecosystems predominantly through a direct pathway from half-hourly to the daily scale, while Ta and VPD occupied the dominant position at single-canopy ecosystem sites. When the aerosol optical depth (AOD) increased, the relative contribution of PARdif increased in multiple-canopy ecosystems and decreased in single-canopy ecosystems; when the sky conditions changed from sunny to cloudy, the relative contribution of PARdif was higher in the forest ecosystem and increased significantly in the grass ecosystem. These findings offer a more comprehensive understanding of the environmental effects of regulating DFE on GPP across ecosystems.

Boosting the lithium storage performance of Na2Li2Ti6O14 anodes by g-C3N4 modification.

Na2Li2Ti6O14 particles were prepared by a simple solid-state process, and then g-C3N4-coated Na2Li2Ti6O14 composites were constructed by a facile solution route for the first time. The g-C3N4-coated Na2Li2Ti6O14 multicomponent composites because of their unique architecture as negative materials for Li-ion batteries can be expected to exhibit a significantly improved cycling stability and reversible capacity even at high rates. g-C3N4 (5 wt%)-coated Na2Li2Ti6O14 shows a discharge (charge) capacity of 184.4 (184.3) mA h g-1 at 500 mA g-1 after 100 cycles, which is larger than that of pristine Na2Li2Ti6O14 with a discharge (charge) capacity of 122.8 (122.0) mA h g-1. The use of g-C3N4 with a carbon framework containing abundant nitrogen provides more active sites and surface defects for redox reactions and Li-ion transport. The g-C3N4 coating decreases the impedance between the electrolyte and Na2Li2Ti6O14 and enhances the charge transfer, ionic conductivity and diffusion ability of Li ions of Na2Li2Ti6O14. This work offers an efficient way to design high-performance Na2Li2Ti6O14-based materials for advanced lithium ion battery, and g-C3N4 (5 wt%)-coated Na2Li2Ti6O14 shows an enormous potential as a negative material for next generation Li-ion batteries with excellent performance.

Simultaneous quantification of candesartan and irbesartan in rabbit eye tissues by liquid chromatography-tandem mass spectrometry.

Diabetic retinopathy is a major cause of vision loss in adults. Novel eye-drop formulations of candesartan and irbesartan are being developed for its cure or treatment. To support a preclinical trial in rabbits, it was critical to develop and validate a new LC-MS/MS method for simultaneous quantification of candesartan and irbesartan in rabbit eye tissues (cornea, aqueous humor, vitreous body and retina/choroid). Eye tissue samples were first homogenized in H2 O-diluted rabbit plasma. The candesartan and irbesartan in the supernatants together with their respective internal standards (candesartan-d4 and irbesartan-d4 ) were extracted by solid-phase extraction. The extracted samples were injected onto a C18 column for gradient separation. The MS detection was in the positive electrospray ionization mode using the multiple reaction monitoring transitions of m/z 441 → 263, 445 → 267, 429 → 207, and 433 → 211 for candesartan, candesartan-d4 , irbesartan and irbesartan-d4 , respectively. For the validated concentration ranges (2-2000 and 5-5000 ng/g for candesartan and irbesartan, respectively), the within-run and between-run accuracies (% bias) were within the range of -8.0-10.0. The percentage CV ranged from 0.6 to 7.3. There was no significant matrix interference nor matrix effect from different eye tissues and different rabbits. The validated method was successfully used in the Good Laboratory Practice (GLP) study of rabbits.

Investigating the urbanization process and its impact on vegetation change and urban heat island in Wuhan, China.

Rapid urbanization significantly changes vegetation coverage and heat distribution, which threatens the sustainable development and the quality of life. As the largest developing city in Central China, Wuhan was chosen as the experimental region. This study investigated the urbanization process of Wuhan from 1989 to 2917 based on Landsat data. Combined with MODIS EVI (Enhanced Vegetation Index) and LST (Land Surface Temperature) data, vegetation disturbance and surface urban heat island (SUHI) caused by urbanization were discussed for 2001-2017. Furthermore, correlation between ∆EVI (urban EVI minus rural EVI) and ∆LST (urban LST minus rural LST) was also conducted. The results were as follows: (1) Wuhan experienced a strong urbanization over the past 29 years, with an increasing urban expansion rate and the altered dominant urban expansion pattern (edge expansion and infilling). After the enhanced vegetation functions and urban increased structures, the urbanization finally caused the fragmented patches and irregular urban shapes. (2) Urbanization had a positive effect on LST but a negative effect on EVI. From 2001 to 2017, the highest increasing rate of ∆LST for the old urban area (OUA) and urbanized area (UA) was both observed in summer daytime (OUA, 0.106 °C/a; UA, 0.207 °C/a). The decreasing rate of ∆EVI reached the highest value in summer (OUA, 0.00697/a; UA, 0.00298/a). (3) There was a strong negative correlation (except spring and winter for OUA) between ∆EVI and ∆LST in daytime, which proved that the activity of vegetation in daytime could relieve LST to a certain extent. This study clarifies the dynamic urbanization process of Wuhan and discusses its impacts on vegetation change and SUHI. Efficiently investigating urbanization process and quantifying its impacts on urban environment are critical for regional ecological conservation.

Improving the selectivity and sensitivity for quantifying 8-α-hydroxy-mutilin in rabbit tissues by using basic mobile phases and negative ionization.

Previously reported LC-MS methods for quantifying 8-α-hydroxy-mutilin (a marker residue of tiamulin) in tissues all used a pseudo MRM transition (from protonated molecular ion to protonated molecular ion, m/z 337→337) due to difficulties in finding a product ion, leading to suboptimal selectivity and sensitivity for detection. By using electrospray negative ionization in a basic medium, we, for the first time, found a highly selective and sensitive true MRM transition for 8-α-hydroxy-mutilin, m/z 335→179. With this newly found MRM transition and the use of pleuromutilin as the internal standard, a very sensitive, selective, and robust LC-MS/MS method has been developed and validated for quantifying 8-α-hydroxy-mutilin in rabbit tissues (muscle, liver, kidney, and fat). In comparison with the previously published methods, the selectivity and sensitivity were significantly improved. For the concentration range validated (0.2-10ppm or 0.2-10µg/g), the within-run and between-run accuracies (% bias) ranged from -5.0 to 3.1 and -4.9 to 3.0, respectively. The% CV ranged from 2.2 to 6.6 and 4.7 to 8.3 for within-run and between-run precisions, respectively. The validated method was successfully used to support two GLP tissue residue depletion studies in rabbits.

Grape seed-derived procyanidins alleviate gout pain via NLRP3 inflammasome suppression.

BACKGROUND: Gout is one of the common inflammatory arthritis which affects many people for inflicting unbearable pain. Macrophage-mediated inflammation plays an important role in gout. The uptake of monosodium urate (MSU) crystals by macrophages can lead to activation of NOD-like receptors containing a PYD 3 (NLRP3) inflammasome, thus accelerating interleukin (IL)-1ß production. Reactive oxygen species (ROS) promoted development of the inflammatory process through NLRP3 inflammasome. Our study aimed to find a food-derived compound to attenuate gout pain via the specific inhibition of the NLRP3 inflammasome in macrophages. METHODS: CD-1 mice were used to evaluate the degree of pain and the swelling dimension of joints after an intra-articular (IA) MSU injection in the ankle. The murine macrophage cell line Raw 264.7 was used to investigate the effects of procyanidins and the mechanism underlying such effects. Histological analysis was used to measure the infiltration of inflammatory cells. ROS produced from Raw 264.7 cells were evaluated by flow cytometry. Cell signaling was measured by Western blot assay and immunofluorescence. RESULTS: Procyanidins significantly attenuated gout pain and suppressed ankle swelling. Procyanidins also inhibited MSU-induced activation of the NLRP3 inflammasome and increase of IL-1ß. Furthermore, procyanidins decreased ROS levels in Raw 264.7 cells. CONCLUSIONS: Suppression of the NLRP3 inflammasome in macrophages contributes to the amelioration of gout pain by procyanidins.

Natural Flavonoids as Promising Analgesic Candidates: A Systematic Review.

Due to the chemical structural diversity and various analgesic mechanisms, an increasing number of studies indicated that some flavonoids from medicinal plants could be promising candidates for new natural analgesic drugs, which attract high interests of advanced users and academic researchers. The aim of this systematic review is to report flavonoids and its derivatives as new analgesic candidates based on the pharmacological evidences. Sixty-four papers were found concerning the potential analgesic activity of 46 flavonoids. In this case, the evidence for analgesic activity of flavonoids and total flavonoids was investigated. Meanwhile, the corresponding analgesic mechanism of flavonoids was discussed by generalizing and analyzing the current publications. Based on this review, the conclusion can be drawn that some flavonoids are promising candidates for painful conditions and deserve particular attention in further research and development.

New phenylpropanoid and other compounds from Illicium lanceolatum with inhibitory activities against LPS-induced NO production in RAW 264.7 macrophages.

Illicium lanceolatum is a traditional Chinese medicine (TCM) for treating inflammatory diseases. Anti-inflammatory activities of I. lanceolatum stems and leaves were tested using ear edema models induced by dimethyl benzene in mice. Bioassay-guided fractionation of the ethanol extract of I. lanceolatum leaves and stems revealed that the ethyl acetate fraction exhibited inhibitory potency to dimethyl benzene-induced edema in the mouse ear. Phytochemical investigation on the active fraction led to the isolation of a new phenylpropanoid (1), together with fifteen known compounds. This is the first report of the isolation of 2-16 from I. lanceolatum. Of these compounds, compounds 1, 2 and 3 showed inhibitory activity on LPS-stimulated NO production in RAW 264.7 macrophages with IC50 values of 27.58, 26.59 and 34.35 µg/mL, respectively. I. lanceolatum stems and leaves can be exploited to alleviate inflammatory diseases, which makes the rare medicinal plant resources sustainable.

Chemical constituents from an endophytic fungus Chaetomium globosum Z1.

A new ergosterol, 15beta-hydroxyl-(22E,24R)-ergosta-3, 5, 8, 22-tetraen-one (1), along with three known ergosterols, two known cytochalasins, and two known azapholines were isolated from Chaetomium globosum Z1. The structures of these compounds were elucidated on the basis of spectroscopic methods (HR-ESI-MS, 1D NMR, and 2D NMR). Compound 6 showed significant cytotoxic activity against A-549 and MG-63 cell lines with IC50 values of 6.96 and 1.73 microg/mL, respectively.

Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery.

The hepatoprotective effect of interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) has been well documented. However, reports on the role of IL-6/STAT3 in liver regeneration are conflicting probably due to the fact that the model of Stat3 knockout mice were complicated with obesity and fatty liver, which may cause some secondary effects on liver regeneration. To study the direct role of STAT3 and to circumvent the problems of obesity and fatty liver in liver regeneration, we generated conditional STAT3 knockout in the liver (L-Stat3(-/-)) using a transthyretin-driven Cre-lox method. The L-Stat3(-/-) mice were born with the expected Mendelian frequency and showed no obesity or other obvious phenotype. After partial hepatectomy, mortality in the L-Stat3(-/-) mice was significantly higher than the littermate Stat3(f/+) controls in the early time points (<24 h). Hepatocyte DNA synthesis in the survived L-Stat3(-/-) mice slightly decreased as compared with Stat3(f/+) mice at 40 h after partial hepatectomy, whereas similar hepatocyte DNA synthesis was found at other time points and liver mass could be completely recovered in the L-Stat3(-/-) mice. In another model of liver regeneration induced by subcutaneous injection of carbon tetrachloride (CCl(4)), hepatocyte DNA synthesis in the CCl(4)-treated L-Stat3(-/-) mice also decreased as compared with Stat3(f/+) mice at 40 h after injection but not at other time points. In addition, infiltration of neutrophils and monocyte increased in the liver of CCl(4)-treated L-Stat3(-/-) mice compared to wild-type mice. In conclusion, STAT3 is required for survival in the acute stage after 70% hepatectomy and plays a role in inflammatory reaction after hepatocyte necrosis. However, the hepatocytic STAT3 may have limited role in liver mass recovery although DNA synthesis may be impaired.

Endothelial cells require STAT3 for protection against endotoxin-induced inflammation.

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E-/-). STAT3E-/- mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E-/- mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor beta. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon gamma. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.

Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age.

Cytokines and inflammation have been implicated in the pathogenesis of heart failure. For example, IL-6 family cytokines and the gp130 receptor play important roles in cardiac myocyte survival and hypertrophy. Signal transducer and activator of transcription 3 (STAT3) is a major signaling protein that is activated through gp130. We have created mice with a cardiomyocyte-restricted deletion of STAT3. As measured by serial echocardiograms, mice with cardiac specific deletion of STAT3 are significantly more susceptible to cardiac injury after doxorubicin treatment than age-matched controls. Intriguingly, STAT3 appears to have a critical role in protection of inflammation-induced heart damage. STAT3-deficient mice treated with lipopolysaccharide demonstrated significantly more apoptosis than their WT counterparts. At the cellular level, cardiomyocytes with STAT3 deleted secrete significantly more tumor necrosis factor in response to lipopolysaccharide than those with WT STAT3. Furthermore, histologic examination of the cardiomyocyte-restricted STAT3-deficient mice reveals a dramatic increase in cardiac fibrosis in aged mice. Although no overt signs of heart failure are present in young STAT3-deficient mice, they spontaneously develop heart dysfunction with advancing age. These results indicate the crucial functions of STAT3 in cardiomyocyte resistance to inflammation and other acute injury and in pathogenesis of age-related heart failure.

Regulation of arterial tone by smooth muscle myosin type II.

The initiation of contractile force in arterial smooth muscle (SM) is believed to be regulated by the intracellular Ca2+ concentration and SM myosin type II phosphorylation. We tested the hypothesis that SM myosin type II operates as a molecular motor protein in electromechanical, but not in protein kinase C (PKC)-induced, contraction of small resistance-sized cerebral arteries. We utilized a SM type II myosin heavy chain (MHC) knockout mouse model and measured arterial wall Ca2+ concentration ([Ca2+](i)) and the diameter of pressurized cerebral arteries (30-100 microm) by means of digital fluorescence video imaging. Intravasal pressure elevation caused a graded [Ca2+](i) increase and constricted cerebral arteries of neonatal wild-type mice by 20-30%. In contrast, intravasal pressure elevation caused a graded increase of [Ca2+](i) without constriction in (-/-) MHC-deficient arteries. KCl (60 mM) induced a further [Ca2+](i) increase but failed to induce vasoconstriction of (-/-) MHC-deficient cerebral arteries. Activation of PKC by phorbol ester (phorbol 12-myristate 13-acetate, 100 nM) induced a strong, sustained constriction of (-/-) MHC-deficient cerebral arteries without changing [Ca2+](i). These results demonstrate a major role for SM type II myosin in the development of myogenic tone and Ca2+ -dependent constriction of resistance-sized cerebral arteries. In contrast, the sustained contractile response did not depend on myosin and intracellular Ca2+ but instead depended on PKC. We suggest that SM myosin type II operates as a molecular motor protein in the development of myogenic tone but not in pharmacomechanical coupling by PKC in cerebral arteries. Thus PKC-dependent phosphorylation of cytoskeletal proteins may be responsible for sustained contraction in vascular SM.