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Active and durable catalysts for hydrogen evolution reaction (HER) are of great significance for developing renewable hydrogen energy. Herein, crystalline/amorphous‐Ru/VOx (c/a‐Ru/VOx) heterogeneous catalysts are conceived, in which the amorphous VOx exposes more active sites and enhances charge transport compared with the counterpart with a crystal phase structure, strengthening the electronic interaction between metal‐support. As expected, c/a‐Ru/VOx‐500 with heat treatment at 500 °C exhibits excellent HER performance under alkaline conditions, with an overpotential of only 33 mV at 10 mA cm−2 and small Tafel slope (27 mV dec−1), superior to commercial platinum/carbon (Pt/C) catalysts. Particularly, its mass activity (0.335 A mgRu−1) is 1.5 times greater than that of Pt/C (0.224 A mgPt−1) at an overpotential of 50 mV. Also, it shows good industrial application prospects through tests under high temperature, high alkalinity, and large current conditions. Theoretical calculations unveil that there exists a charge redistribution at c/a‐Ru/VOx heterointerfaces, which makes the surface of Ru takes on an electron‐deficient state, resulting in optimization of adsorption and desorption for different reaction intermediates. This optimized behavior effectively reduces the thermodynamic energy barrier, allowing the catalyst with greatly enhanced HER performance. The exploration provides a promising strategy for designing efficient and durable catalysts for HER. [ABSTRACT FROM AUTHOR]

Objectives: Residual varus after total knee arthroplasty (TKA) can affect functional outcomes, which may worsen in the presence of obesity. However, no studies were found to compare the outcomes of obese patients involving postoperative residual mild varus or neutral. The aim of this study was to compare postoperative complications and prosthesis survival, and functional outcomes for knees of obese patients with neutral or mild varus after TKA. Methods: We retrospectively reviewed 188 consecutive obese patients (body mass index ≥30 kg/m2) at our hospital who underwent TKA due to varus knee osteoarthritis from January 2010 to December 2015. The mechanical hip‐knee‐ankle axis angle was measured in all patients at admission and discharge. Knee functions were retrospectively assessed based on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Knee Society Knee Score (KS‐KS), Knee Society Function Score (KS‐FS), Forgotten Joint Score (FJS), and range of motion (ROM). Continuous data were compared between knees with neutral or mild varus alignment using analysis of Student's t test or variance or the Kruskal–Wallis test as appropriate. For multiple comparisons of outcomes, we used Bonferroni–Dunn method to adjust p‐values. Categorical data were compared using the chi‐squared test. Results: Of the 156 knees in 137 obese patients who completed follow‐up for a mean of 8.32 ± 1.47 years, 97 knees were corrected from varus to neutral and 54 knees were kept in mild residual varus. Patients with mild varus knees had significantly WOMAC (8.25 ± 8.637 vs. 14.97 ± 14.193, p = 0.009) and better FJS (86.03 ± 15.607 vs. 70.22 ± 30.031, p = 0.002). The two types of knees did not differ significantly in KS‐KS, KS‐FS, or ROM. Although one patient with a neutral knee had to undergo revision surgery, there was no significant difference between two groups. Conclusions: For obese patients with osteoarthritis, preservation of residual varus alignment after TKA can improve functional outcomes without compromising prosthesis survival. [ABSTRACT FROM AUTHOR]

Low‐dimensional organic–inorganic metal halides (OIMHs) have emerged as promising light emitters due to their broadband emission originating from self‐trapped excitons (STE), especially for Cu‐based OIMHs. Herein, Cu(I)‐based OIMH with a structure of (TPP)2Cu4I6·2DMSO (TPP stays for tetraphenylphosphonium, and DMSO – for dimethyl sulfoxide) has been synthesized, both in form of single crystals and as a microcrystalline powder. This compound exhibits a broadband green emission with a peak at 515 nm and a full width at half‐maximum of 78 nm, and a near‐unity photoluminescence quantum yield of 99.5%. Experimental data supported by theoretical calculations indicate that the STE emission is responsible for the green emission with a long lifetime of 2.53 µs. Down‐conversion light‐emitting device with a high luminous efficiency of 50 lm W−1 based on this compound have been fabricated, and white light has also been achieved with a high color rendering index of 96.7. Moreover, green emissive (TPP)2Cu4I6·2DMSO is utilized in scintillators for X‐ray detection and imaging, and as a luminescent ink for encryption applications. [ABSTRACT FROM AUTHOR]

Exploring rapid, sensitive, and multifunctional biosensors is of great significance in medical diagnosis and biotechnology, while creating Cu‐N‐C center‐based enzymatic biodetection system is still a great challenge for colorimetric biosensing fields. Herein, inspired by the axial coordination structure of the natural enzyme, an efficient and specific Cu‐N‐C center‐based peroxidase‐like biocatalyst is created via axial strong‐metal‐support‐interaction (SMSI) between WOx support and Cu‐Nx‐based carbon shell, denoted as Cu‐NC‐WO3. This analysis discloses that the SMSI effect induces electron transfer from Cu to WOx, thus making the valence state of Cu higher and consequently suppressing the O intermediates' adsorption. Owing to this unique structure, the Cu‐NC‐WO3 exhibits exceptional peroxidase (POD) like activities (Km = 3.57 × 10−3m, Vmax = 13.80 × 10−6m s−1, and turnover number (TON) = 206.13 × 10−3 s−1 for H2O2), which is more efficient than the other Cu‐Nx center‐based biocatalysts and also many recently reported peroxidase‐like nanomaterials. Meanwhile, this Cu‐NC‐WO3 shows substrate selectivity, low detection limit, and high resistance to extreme environments for abundant H2O2‐related biomarkers, which are revealed by colorimetric studies. Thus, as a helpful method for accurate biodetection, it is believed this work promises to offer rapid, specific, and inexpensive colorimetric biosensors for regions with bare medical resources, as well as new strategies for the structural engineering of enzyme‐like biocatalysts. [ABSTRACT FROM AUTHOR]

Background and Purpose: Patients suffering from trigeminal neuralgia are often accompanied by anxiety and depression. Microglia‐mediated neuroinflammation is involved in the development of neuropathic pain and anxiodepression pathogenesis. Whether and how microglia are involved in trigeminal neuralgia‐induced anxiodepression remains unclear. Experimental Approach: Unilateral constriction of the infraorbital nerve (CION) was performed to establish trigeminal neuralgia in rat and mouse models. Mechanical allodynia and anxiodepressive‐like behaviours were measured. Optogenetic and pharmacological manipulations were employed to investigate the role of hippocampal microglia in anxiety and depression caused by trigeminal neuralgia. Key Results: Trigeminal neuralgia activated ipsilateral but not contralateral hippocampal microglia, up‐regulated ipsilateral hippocampal ATP and interleukin‐1β (IL‐1β) levels, impaired ipsilateral hippocampal long‐term potentiation (LTP) and induced anxiodepressive‐like behaviours in a time‐dependent manner in rodents. Pharmacological or optogenetic inhibition of ipsilateral hippocampal microglia completely blocked trigeminal neuralgia‐induced anxiodepressive‐like behaviours. Activation of unilateral hippocampal microglia directly elicited an anxiodepressive state and impaired hippocampal LTP. Knockdown of ipsilateral hippocampal P2X7 receptors prevented trigeminal neuralgia‐induced microglial activation and anxiodepressive‐like behaviours. Furthermore, we demonstrated that microglia‐derived IL‐1β mediated microglial activation‐induced anxiodepressive‐like behaviours and LTP impairment. Conclusion and Implications: These findings suggest that priming of microglia with ATP/P2X7 receptors in the ipsilateral hippocampus drives pain‐related anxiodepressive‐like behaviours via IL‐1β. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia‐induced anxiety and depression was uncovered. The approaches targeting microglia and P2X7 signalling might offer novel therapies for trigeminal neuralgia‐related anxiety and depressive disorder. [ABSTRACT FROM AUTHOR]

Metal-porphyrins or metal-phthalocyanines-based organic frameworks (POFs), an emerging family of metal-N-C materials, have attracted widespread interest for application in electrocatalysis due to their unique metal-N4 coordination structure, high conjugated π-electron system, tunable components, and chemical stability. The key challenges of POFs as high-performance electrocatalysts are the need for rational design for porphyrins/phthalocyanines building blocks and an in-depth understanding of structure-activity relationships. Herein, the synthesis methods, the catalytic activity modulation principles, and the electrocatalytic behaviors of2D/3D POFs are summarized. Notably, detailed pathways are given for modulating the intrinsic activity of the M-N4 site by the microenvironments, including central metal ions, substituent groups, and heteroatom dopants. Meanwhile, the topology tuning and hybrid system, which affect the conjugation network or conductivity of POFs, are also considered. Furthermore, the representative electrocatalytic applications of structured POFs in efficient and environmental-friendly energy conversion areas, such as carbon dioxide reduction reaction, oxygen reduction reaction, and water splitting are briefly discussed. Overall, this comprehensive review focusing on the frontier will provide multidisciplinary and multi-perspective guidance for the subsequent experimental and theoretical progress of POFs and reveal their key challenges and application prospects in future electrocatalytic energy conversion systems. [ABSTRACT FROM AUTHOR]

Though numerous nanomaterials with enzyme‐like activities have been utilized as probes and sensors for detecting biological molecules, it is still challenging to construct highly sensitive detectors for biomarkers using polymeric materials. Benefiting from the π‐d delocalization effect of electrons, excellent metal‐chelating property, high electron transferability, and good chemical stability of π‐conjugated phthalocyanine, the design of the copper phthalocyanine‐based conjugated polymer nanoparticles (Cu‐PcCP NPs) as a colorimetric sensor for a variety of biomarkers is reported. The Cu‐PcCP NPs are synthesized through a simple microwave‐assisted polymerization, and their chemical structures are thoroughly characterized. The colorimetric results of Cu‐PcCP NPs demonstrate excellent peroxidase‐like detecting activity and also great substrate selectivity than most of the reported Cu‐based nanomaterials. The Cu‐PcCP NPs can achieve a detection limit of 4.88 μM for the H2O2, 4.27 μM for the L‐cysteine, and 21.10 μM for the glucose via a cascade catalytic system, which shows comparable detecting sensitivity as that of many earlier reported enzyme‐like nanomaterials. Moreover, Cu‐PcCP NPs present remarkable resistance to harsh conditions, including high temperature, low pH, and excessive salts. These highly specific π‐conjugated copper‐phthalocyanine nanoparticles not only overcome the current limitation of polymeric material‐based sensors but also provide a new direction for designing next‐generation enzyme‐like nanomaterial‐based colorimetric biosensors. [ABSTRACT FROM AUTHOR]

Over the last few decades, much of the desert‐oasis ecotone in northwestern China has been reclaimed for cotton cultivation. However, we still know little about the composition of the soil bacterial community relative to soil chemical properties in reclaimed soil after long‐term monocultural cotton production in arid and extremely arid areas. Here, we collected soil samples from two farms where cotton has been continuously planted for more than 20 years. We found that the composition of the soil bacterial communities was significantly different between these two farms, variance in which could be explained by available K, N, and P, total N, and soil pH. The relative abundance of Verrucomicrobia was significantly higher at the Xinhu farm, while Bacteroidetes and Nitrospirae predominated at the Tenth farm. Across sites, the abundance of Bacteroidetes was positively correlated with available N and P, while the abundance of Verrucomicrobia was positively correlated with total N and available K. Moreover, bacterial community diversity, as quantified via phylogenetic diversity, Shannon diversity, and operational taxonomic unit richness, was higher at the Tenth farm. These soil bacterial diversities were all positively correlated with available N, but negatively correlated with available K in arid and extremely arid areas. Our results suggest that available K, N, and P, total N, and pH are all key factors in shaping soil bacterial communities. The influence of available N and K on bacterial community diversity should therefore be considered for cotton cultivation in reclaimed soil. [ABSTRACT FROM AUTHOR]

Cardinium and Wolbachia are maternally inherited bacterial symbionts of arthropods that can manipulate host reproduction by increasing the fitness of infected females. Here, we report that Cardinium and Wolbachia coinfection induced male‐killing and cytoplasmic incompatibility (CI) when they coexisted in a cryptic species of whitefly, Bemisia tabaci Asia II7. Cardinium and Wolbachia symbionts were either singly or simultaneously localized in the bacteriocytes placed in the abdomen of B. tabaci nymphs and adults. Cardinium–Wolbachia coinfection induced male‐killing and resulted in a higher female sex ratio in the intraspecific amphigenetic progeny of Asia II7 ICWH and ICWL lines; interestingly, male‐killing induction was enhanced with increased Cardinium titer. Moreover, single infection of Wolbachia induced partial CI in the Asia II7 IW line and resulted in reduced fecundity, higher embryonic mortality, and lower female sex ratio. The uninfected Asia II7 IU line had significantly higher fecundity, lower embryonic and nymphal mortalities, and a lower level of CI than both the Wolbachia‐infected Asia II7 IW line and the Cardinium–Wolbachia‐coinfected Asia II7 ICWH line. Our findings indicate that Cardinium–Wolbachia coinfection induced male‐killing, which may have had antagonistic effects on Wolbachia‐induced CI in the Asia II7 whiteflies. For the first time, our study revealed that B. tabaci Asia II7 reproduction is co‐manipulated by Cardinium and Wolbachia endosymbionts. [ABSTRACT FROM AUTHOR]

Utilization of the confined cavity of the mesoporous silica, the exploration of the synergetic catalysis process for sequential organic transformations has great significance in asymmetric catalysis. In this study, the yolk‐shell‐structured magnetic nanoparticles with the chiral Ru/diamine species within the nanochannels of the outer mesoporous silica shell and the FeCl3 species on the inner magnet core are fabricated. The electron microscopy images and the structural characterizations disclose the uniformly distributed magnetic nanoparticles with the well‐defined single‐site ruthenium/diamine active centers onto the outer silica shell. As a yolk‐shell‐structured bifunctional magnet catalyst, the FeCl3 species enables an efficient aerobic oxysulfonylation between aryl‐substituted terminal alkynes and sodium sulfinates to the β‐keto sulfones intermediates, and the ruthenium/diamine species sequentially reduces the in‐situ generated intermediate to the chiral β‐hydroxysulfones products. As we envision, this one‐pot aerobic oxysulfonylation/asymmetric transfer hydrogenation process affords various chiral β‐hydroxysulfones in high yields with excellent enantioselectivities. Furthermore, this magnetic catalyst can also be conveniently recovered via an additional outer magnet and repeatedly recycled, showing a potential application in industrial interest. [ABSTRACT FROM AUTHOR]

E3 ubiquitin ligases primarily determine the substrate specificity of the ubiquitin‐proteasome system and play an essential role in the resistance to bortezomib in multiple myeloma (MM). Neural precursor cell‐expressed developmentally downregulated gene 4‐1 (NEDD4‐1, also known as NEDD4) is a founding member of the NEDD4 family of E3 ligases and is involved in the proliferation, migration, invasion and drug sensitivity of cancer cells. In the present study, we investigated the role of NEDD4‐1 in MM cells and explored its underlying mechanism. Clinically, low NEDD4‐1 expression has been linked to poor prognosis in patients with MM. Functionally, NEDD4‐1 knockdown (KD) resulted in bortezomib resistance in MM cells in vitro and in vivo. The overexpression (OE) of NEDD4‐1, but not an enzyme‐dead NEDD4‐1‐C867S mutant, had the opposite effect. Furthermore, the overexpression of NEDD4‐1 in NEDD4‐1 KD cells resensitized the cells to bortezomib in an add‐back rescue experiment. Mechanistically, pAkt‐Ser473 levels and Akt signaling were elevated and decreased by NEDD4‐1 KD and OE, respectively. NEDD4‐1 ubiquitinated Akt and targeted pAkt‐Ser473 for proteasomal degradation. More importantly, the NEDD4‐1 KD‐induced upregulation of Akt expression sensitized MM cells to growth inhibition after treatment with an Akt inhibitor. Collectively, our results suggest that high NEDD4‐1 levels may be a potential new therapeutic target in MM. What's new? While multiple myeloma (MM) remains an incurable disease, therapeutic advances have greatly improved its clinical management. Among the agents most effective against MM is the proteasome inhibitor bortezomib, though many patients eventually develop drug resistance. Here, decreased expression of the tumor suppressor NEDD4‐1 was found to serve a key role in modulating MM sensitivity to bortezomib. Reduced NEDD4‐1 expression was associated with increased PTEN/PI3K/Akt signaling and tumor growth. Experiments showed that NEDD4‐1 normally binds directly to Akt, enhancing its ubiquitination and thereby exerting anti‐MM effects. The data warrant further investigation of NEDD4‐1 reactivation as a novel therapeutic strategy for MM. [ABSTRACT FROM AUTHOR]

Light scattering detection in microfluidic chips provides an important tool to identify cancer cells without any label processes. However, forward small‐angle scattering signals of cells, which are related to their sizes and morphologies, are hard to be detected accurately when scattering angle is less than 11° in microfluidic chips by traditional lighting design due to the influence of incident beam. Therefore, cell's size and morphology being the golden standard for clinical detection may lose their efficacy in recognizing cancer cells from healthy ones. In this article, a novel lighting design in microfluidic chips is put forward in which traditional incident Gaussian beam can be modulated into quasi‐Bessel beam by a microprism and waveguide. The quasi‐Bessel beam's advantages of nondiffraction theoretically make forward scattering (FS) detection less than 11° possibly. Our experimental results for peripheral blood lymphocytes of human beings and cultured HeLa cells show that the detection rates increase by 47.87% and 46.79%, respectively, by the novel designed microfluidic chip compared to traditional Gaussian lighting method in microfluidic chips. © 2019 International Society for Advancement of Cytometry [ABSTRACT FROM AUTHOR]

The heterogeneity and immunosuppression microenvironment of ovarian cancer seriously restrict the efficiency of monomodal treatment. Emerging multimodal therapy strategies based on sonodynamic therapy with enhanced antitumor effects have attracted intensive attention in the quest to combat cancer. However, exploring highly efficient sonosensitizers integrating chemodynamic/sonodynamic/immunotherapies with reversing immunosuppressive tumor microenvironment (TME) capacity is urgently desired but remains challenging. Here, a facile strategy is designed to synthesize immunomodulating sonocatalytic nanoagents (IrT‐SCN) with dual‐functional Ir‐N centers and narrow bandgap for reversing immunosuppression and potentiating ovarian cancer immunotherapy. IrT‐SCN with dual‐functional centers Ir‐N2 and Ir‐N4 and conjugated networks show a reduced bandgap, moderate interaction with H2O2, and efficient production of reactive oxygen species (ROS). Such ROS capabilities include: 1) utilizing H2O2 in TME to catalytically generate potent O2, as well as abundant superoxide anion (•O2−) and singlet oxygen (1O2) radicals; 2) external ultrasound (US) irradiation can also boost the production of 1O2 simultaneously; 3) M1 polarization of tumor‐associated macrophages and enhanced immune effect can promote the outcome of cancer treatment. This finding provides proof‐of‐concept evidence for the future development of immunomodulating sonocatalytic nanoagents for oncological treatments and other ROS‐related biomedical fields. [ABSTRACT FROM AUTHOR]

Abstract: Phosphine‐relayed olefination and aza‐Wittig reactions of readily available aldehydes with 2,2,2‐trifluorodiazoethane (CF3CHN2) have been realized. This protocol enables the facile construction of a series of trifluoromethylated alkenes and hydrazones in good to high yield under mild conditions. [ABSTRACT FROM AUTHOR]

HER2 receptor dimerization is a critical step in the HER2 activation process. Here, we demonstrated that heat shock protein gp96 on cell membrane interacts with HER2, facilitates HER2 dimerization and promotes cell proliferation. Cell membrane gp96 levels were observed to correlate with HER2 phosphorylation in primary breast tumors. Finally, we provide evidence that targeting gp96 with a specific monoclonal antibody led to decreased cell growth and increased apoptosis in vitro, and suppression of tumor growth in vivo. Our work represents a new therapeutic strategy for inhibiting HER2 signaling in cancer. [ABSTRACT FROM AUTHOR]

Background The aim of the study was to characterize the histological and epidemiological features of lung cancer in Chinese women. Methods Demographic and histological information on female lung cancer cases identified during 1 January 2000 through 31 December 2012 from the Cancer Hospital of the Chinese Academy of Medical Sciences were collected. The International Classification of Diseases for Oncology system was used to classify the histological subtypes. Relative frequencies ( RF) were estimated for major histological subtypes and compared by the years of diagnosis and birth, and among residential areas. Statistical differences were tested for RFs in the time periods with a trend test and with Pearson Chi square tests for distribution. Results Of 7070 female Chinese lung cancer cases, the major histological subtypes were adenocarcinoma ( ADC) 65.79%; squamous cell carcinoma ( SCC) 10.21%; small cell cancer 8.12%; large cell carcinoma, 2.79%; and adeno-squamous carcinoma ( ASC), 2.19%. ADC increased, with RFs from 46.72% in the cases identified in 2000-2002 to 76.49% in 2011-2012 ( Z = 16.998, P < 0.0001); SCC decreased from 15.69% to 5.97% ( Z = −8.750, P < 0.0001). Compared to the cases identified in 2000-2006, the age-adjusted RFs of ADC in 2007-2012 consistently increased in all study areas. Conclusion The significant increase of ADC of the lung in Chinese women suggests that a persistently strong exposure to potential carcinogens in the Chinese population should be further and fully investigated. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown that Herpes Simplex Virus thymidine kinase (HSV-tk)/ganciclovir (GCV) comprised the most commonly used suicide gene therapy for prostate cancer, with modest results being obtained. However, novel suicide genes, such as Escherichia coli purine nucleoside phosphorylase (PNP), have been utilized to demonstrate more potent tumor killing and an enhanced bystander effect on local, non-expressing cells compared to HSV-tk. Methods PNP/fludarabine (Fludara®; fludarabine phosphate; Berlex Labs, Richmond, CA, USA) was deliveried by prostate-specific, rat probasin-based promoter, ARR2PB. After infection of various cell lines with ADV.ARR2PB-PNP and administration of androgen analog, R1881, expression of PNP mRNA was detected; in vivo, the antitumor effect of the ARR2PB-PNP/Fludara system was monitored and analyzed, as well as animal survival. Results After in vitro infection with ADV.ARR2PB-PNP (multiplicity of infection = 10), LNCaP cells were more sensitive to a lower concentration Fludara (LD50, approximately 0.1 µg/ml) in the presence of R1881. Furthermore, robust bystander effects after R1881/Fludara treatment were observed in LNCaP cells after infection with bicistronic vector ADV.ARR2PB/PNP-IRES-EGFP in contrast to a much weaker effect in cells treated with ADV.CMV-HSV-tk/GCV. In vivo, tumor size in the ADV.ARR2PB-PNP/Fludara treatment group was dramatically smaller than in the control groups, and the mice treated with our system had a significantly prolonged survival, with three of eight mice surviving up to the 160-day termination point, as well as no systemic toxicity. Conclusions The ARR2PB-PNP/Fludara system induced massive tumor cell death and a prolonged life span without systemic cytotoxicity; therefore, it might be a more attractive strategy for suicide gene therapy of prostate cancer. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Organic–inorganic copper(I) halides (OICHs) have recently attracted great attentions for their unique optoelectronic properties. However, most of them have poor stability and narrow excitation in UV region, which seriously hinder their applications in efficient white light‐emitting diodes (WLEDs). Herein, 0D (C19H18P)2Cu4I6 with super broad‐band excitation (300–500 nm) and yellow emission with the absolute photoluminescence quantum yield of 87.4% is synthesized in a quantity of gram scale. Specifically, (C19H18P)2Cu4I6 possesses exceptional thermal‐, photo‐, air‐stability, and can maintain efficient emission even if soaked in water, ethyl acetate, and isopropanol over 30 days. WLEDs with remarkable color stability under various driven currents are fabricated using 450, 400, 365, and 310 nm LED chips. The ideal WLEDs based on single (C19H18P)2Cu4I6 by 450 nm LED chip presents high color rendering index of 86.7, and outstanding luminous efficiency of 90 lm W−1. To the best of the knowledge, this is the highest value that is achieved based on single‐component OICHs using blue light chip. This work not only promotes the prospect of OICHs in WLEDs but also significantly broadens their application in special lighting fields, such as underwater illumination. [ABSTRACT FROM AUTHOR]

There is a current view that myosin light chain kinase (MLCK) plays a critical role in endothelial permeability. To investigate the functions of MLCK in endothelial cells in vivo, we generated a mouse model in which MLCK was selectively deleted by crossing Mylk1 floxed mice with Tie2/cre transgenic mice. Knocking out Mylk1 from endothelial cells had no effect on the global phenotype of the mice, including body weight and blood pressure. Lipopolysaccharide (LPS)-mediated septic death was also not altered in the knockout (KO) mice. Consistently, LPS-induced inflammatory injury and the increase in microvascular permeability in the main organs, including the lung and the kidney, was not significantly attenuated in KO mice as compared with wild-type mice. However, the LPS-induced microvascular hyperpermeability of the esophagus and the eyeballs was attenuated in KO mice. We also found that the LPS-mediated increase in the number of caveolae in the endothelial cells of the esophagus was significantly reduced in KO mice. Our results do not support a role for endothelial cell MLCK in the pathogenesis of inflammatory diseases. [ABSTRACT FROM AUTHOR]