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Establishing the structure of porphyrins with a A-π-D-π-A configuration is one of the effective strategies to maintain their dominance and compensate shortcomings through flexible changes in fragments. In this regard, π-bridges have attracted wide attention as a parameter affecting molecular backbones, electron transfer, energy levels, absorption, and other properties. However, the essence and influence of π-bridges have not yet been confirmed. In order to satisfy the requirements of intelligent application in molecular design, this study aimed to investigate the control effect of differences in π-bridge composition (thiophene and selenophene) and connection type (single bonds, ethylenic bonds and fused) on photoelectric performance. Y6 and PC 61 BM were used as acceptors to build donor/acceptor (D/A) interfaces and characterize the film morphology in three dimensions. Results showed that the essence of π-bridges involves a strong bridging effect (adjusting ability) between A and D fragments rather than highlighting its own nature. The large value could obtain high open circuit voltages ( V OC ), large separation and small recombination rates as well as stable and tight morphology. Therefore, adjusting ability is a unified descriptor for evaluating π-bridges, and it is an effective strategy to adjust material properties and morphology. This insight and discovery may provide a new evaluation descriptor for the screening and design of π-bridges.

Few intrapericardial robotic lung resection cases have been reported in the literature because of the perceived complexity of the procedure, with most surgeons embarking on an open resection via a thoracotomy. We present the case of a right middle and lower lobe tumour involving the pericardium and the origin of the right middle lobe vein. An intrapericardial lower bilobectomy was performed, with pericardial resection, pre-pericardial fat resection and mesh reconstruction. The vascular stapler for the right middle lobe vein was fired on the atrium. The resection was completed via a retrograde and fissureless approach, dividing the bronchus intermedius first, because it was impossible to open the fissure, leaving the division of the pulmonary artery until last. The case was performed solely robotically, with no complications and excellent postoperative recovery. Robotic resection can be performed successfully when pericardial lung tumours are involved., (© The Author 2024. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objective: To investigate the pathogenesis and clinical efficacy of arthroscopic treatment for hallux ganglion cyst deriving from ankle joint. Methods: The clinical data of 21 patients with ankle arthroscopic in the Department of Hand and Foot Surgery,Affiliated Hospital of Jining Medical College from January 2019 to March 2021 were analyzed retrospectively.There were 15 male and 6 female cases,aged (52.6±8.2) years (range:42 to 70 years).There were 9 cases of primary operation and 12 cases of recurrence after operation in other hospital.All the patients were examined by ankle arthrography and MRI before operation.The synovial membrane of the ankle was debrided and the tendon sheath of flexor longus was removed at the ankle canal.One year after operation,MRI was performed,and the American Orthopedic Foot and Ankle Society(AOFAS) score of forefoot function and visual analogue scale (VAS) before and after operation were compared by the paired t test or Mann-Whitney U test.The postoperative complications and recurrence were recorded. Results: All patients were operated successfully.The joint capsule at the back of the ankle joint of the patients were ruptured and communicated with the tendon sheath of the flexor longus tendon at the ankle canal.No wound infection,vascular and nerve injury occurred.The follow-up period was (15.0±2.2) months (range:12 to 18 months).During the follow-up period,there was no recurrence of toe appearance and MRI.At the last follow-up,the AOFAS score (90.8±4.3) was significantly higher than that (72.8±6.3) before operation ( t =-10.810, P <0.01),and the VAS score( M (IQR)) was significantly lower than that before operation,the difference was significant (1.0(1.0) vs. 3.0(0.5), Z =-4.081, P <0.01). Conclusions: The possible mechanism of hallux ganglion cyst deriving from ankle joint is that the joint capsule at the back of the ankle joint ruptures and communicates with the tendon sheath of the flexor longus tendon at the ankle canal,and the intra-articular synovial fluid through the cylinder effect generated by sliding with the flexor tendon of the flexor longus tendon in the tendon sheath sac leads to the heel valange cyst.Ankle-synovial cleansing of the ankle joint under ankle arthroscopy and resection of the flexor tendon sheath of the flexor longus tendon at the ankle canal are effective and less invasive.

Objective: To evaluate the value of high-resolution ultrasound the diagnosis and prognosis of cubital tunnel syndrome., Methods: From January 2018 to June 2019, 47 patients with cubital tunnel syndrome were treated with ulnar nerve release and anterior subcutaneous transposition. There were 41 males and 6 females, aged from 27 to 73 years old. There were 31 cases on the right, 15 cases on the left, and 1 case on both sides. The diameter of ulnar nerve was measured by high-resolution ultrasound pre-and post-operatively, and measured directly during the operation. The recovery status of the patients was evaluated by the trial standard of ulnar nerve function assessment, and the satisfaction of the patients was assessed., Results: All the 47 cases were followed up for an average of 12 months and the incisions healed well. The diameter of ulnar nerve at the compression level was (0.16±0.04) cm pre-operatively, and the diameter of ulnar nerve was (0.23±0.04) cm post-operatively. The evaluation of ulnar nerve function:excellent in 16 cases, good in 18 cases and fair in 13 cases. Twelve months post-operatively, 28 patients were satisfied, 10 patients were general and 9 patients were dissatisfied., Conclusion: The preoperative examination of ulnar nerve by high-resolution ultrasound is consistent with the intuitive measurement during operation, and the result of postoperative examination of ulnar nerve by high-resolution ultrasound is consistent with follow-up results. High-resolution ultrasound is an effective auxiliary method for the diagnosis and treatment of cubital tunnel syndrome.

Problem: Endometriosis patients undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment suffer from poor oocyte quality, a reduced likelihood of the fertilization rate, and low embryo quality. The dysregulation of immune cells and cytokine profiles in the follicular fluid (FF) may play an important role in the competence of the oocyte and the development of the embryo, but the mechanism remains largely unknown., Method of Study: A total of 40 proved advanced staged endometriosis patients were enrolled in this study. The pregnancy results were followed until all the embryos collected by the first oocyte retrieval cycle were used up. The immune cells subtypes in FF and serum collected on the day of oocyte retrieval were detected by flow cytometry and 27 cytokines were determined using the Bio-Plex Pro Human Cytokine 27-Plex Immunoassay. The specific effect of cytokine on the gene expression of human granulosa cells was determined by RT-qPCR., Results: The fertilization rate and the cumulative live birth rate were significantly lower in the endometriosis group. The ratio of CD4 + /CD8 + T cells in FF was significantly lower, while the level of IP-10, RANTES and G-CSF were statistically higher in the endometriosis group. The level of IP-10 correlated with the IVF outcome. Moreover, treated by IP-10, the mRNA level of FSHR and CYP19A1 the human granulosa cells were downregulated in vitro., Conclusion: These results suggest that alterations of the lymphocyte subsets and cytokines in women with advanced endometriosis may have an impact on the oocyte development and resulting in poorer IVF outcomes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Carpal tunnel syndrome (CTS) has been associated with gout and type 2 diabetes mellitus (T2DM). However, due to insufficient clinical understanding of gout-related CTS and reliance on the diagnostic importance of elevated serum uric acid levels, such cases are prone to missed diagnosis, misdiagnosis, and delayed treatment. In addition, the effect of T2DM on gout - induced carpal tunnel syndrome has not been reported., Case Summary: Herein, we present an unusual case of CTS and motor dysfunction caused by miliary tophaceous gout and T2DM. The patient presented to the hand and foot clinic with paresthesia of the fingers of both hands, especially at night. The patient was diagnosed with type 2 diabetes a month ago. Ultrasonography revealed bilateral transverse carpal ligament thickening with median nerve compression during hospitalization. The patient was successfully treated with carpal tunnel decompression and tendon release. The postoperative pathological examination revealed typical gout nodules. This case suggests that the presence of T2DM could accelerate tophi formation and worsen CTS symptoms, although no definitive proof in this regard has been described previously., Conclusion: Tophi formation may most likely cause the co-occurrence of CTS and flexor dysfunction in gout and incipient diabetes patients., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Prostate cancer is one of the most lethal malignancies, and androgen deprivation therapy remains the mainstay of treatment for prostate cancer patients. Although androgen deprivation can initially come to remission, the disease often develops into castration-resistant prostate cancer (CRPC), which is still dependent on androgen receptor (AR) signaling and is related to a poor prognosis. Some success against CRPC has been achieved by drugs that target AR signaling, but secondary resistance uninterrupted emerges, and new therapies are urgently needed. In this study, we identified a potent small molecule compound, ZY-444, that suppressed PCa cells proliferation and metastasis, and inhibited tumor growth both in subcutaneous. Transcriptome sequencing analysis showed that TNFAIP3 was significantly elevated in prostate cancer cells after ZY-444 treatment. Further studies through overexpression of TNFAIP3 confirmed that TNFAIP3, as a direct target gene of ZY-444, contributes to the functions of ZY-444. In addition, we demonstrated the effects of TNFAIP3 on prostate cancer cell apoptosis, migration and proliferation to elucidate the mechanism of ZY-444. We found that TNFAIP3 inhibited the TNF signaling pathway, which could inhibit cell migration and proliferation and contribute to apoptosis. Overall, these findings highlighted TNFAIP3 as a tumor suppressor gene in the regulation of the progression and metastatic potential of prostate cancer and that targeting TNFAIP3 by ZY-444 might be a promising strategy for prostate cancer treatment., Competing Interests: None., (AJCR Copyright © 2023.)

Problem: During the first trimester, the accumulation of macrophages, which is the second largest decidual leukocyte population (~20%) at the maternal-fetal interface, is quite vital for a successful pregnancy, including embryo implantation, trophoblast invasion, and vascular remodeling. The mechanism of the enrichment and redistribution of macrophages in the uterine decidua of early pregnancy is largely unclear., Method of Study: A total of 37 women with normal early pregnancies were included. Primary decidual macrophages (dMφs) (n = 37) and primary decidual stromal cells (DSCs) (n = 37) were isolated, and the adhesion molecules were analyzed by flow cytometry (FCM). Adhesive experiment was carried out to evaluate the adhesion capacity by counting cell numbers of dMφs adhered to DSCs in a co-culture system., Results: We found that RANK + dMφs was the dominating subtype at the maternal-fetal interface. The expression of adhesion molecules (eg, CD29, CD31, CD54, and CD62L) on the surface of RANK + dMφs was higher than that of RANK - dMφs. After co-culture with DSCs, the expression of adhesion molecules on dMφs was up-regulated in a RANKL-dependent manner. Meanwhile, dMφs promoted the releasing of RANKL on DSCs after co-culture. Consistently, dMφs exhibited the lessoned capacity of adhesion to DSCs when blocking the crosstalk of RANKL-RANK between the DSCs and dMφs in vitro., Conclusion: These results suggest that the interaction of RANKL-RANK up-regulates the expression of adhesion molecules on the surface of dMφs, contributing to the accumulation and residence of dMφs in human early pregnancy., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A 64-year-old man presented with reduced vision in the right eye (visual acuity of 6/24 Snellen). The patient reported having a chronic cough and recent weight loss with difficulty in swallowing and abnormal liver function test 8 months prior to his presentation. He was a chronic smoker for 45 years, having quit a year earlier. Fundus examination showed a unifocal large yellow-brown subretinal mass involving the posterior segment of the eye and associated with subretinal fluid. The patient was diagnosed with a choroidal metastasis and was referred urgently to the oncology team who confirmed the presence of non-small cell lung cancer with distant metastases. He started treatment with alectinib (second-generation tyrosine kinase inhibitor). A few weeks later, his vision improved and, on examination, there was complete resolution of the choroidal mass and the associated subretinal fluid. Alectinib led to rapid resolution of his choroidal secondary and has excellent ocular safety profile., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Artemisia rupestris L. is the perennial herb of rupestris belonging to Artemisia (Compositae), which is wildly distributed in Xinjiang (China), middle Asia, and Europe. It is known to have anti-inflammatory, hepatoprotective, immune function regulation, and gastrointestinal function regulation effects. AR is used to treat digestive diseases, but the effects of AR on antifunctional dyspepsia (FD) activity have not yet been reported. In this study, we aimed to investigate the therapeutic effects of Artemisia rupestris L. extract (ARE) on gastrointestinal hormones and brain-gut peptide in functional dyspepsia (FD) rats. Sixty Sprague-Dawley rats were randomly divided into 6 groups. An FD rat model was established by irregular tail clamp stimulation for 14 days except the blank group. After FD rat models, the blank group and model group were given menstruum, and the medicated rats were given corresponding medicine for 14 days. The general observations, bodyweight, and food intake were observed, and the content of serum gastrin (GAS), plasma motilin (MTL), plasma vasoactive intestinal peptide (VIP), and plasma somatostatin (SS) by the enzyme-linked immunosorbent assay was observed. The content of plasma VIP and plasma SS in the ARE group was significantly lower than in the model group, and the content of serum GAS and plasma MTL was increased in the ARE group; the GAS expression of antrum and hypothalamus was increased in the ARE group, and SS expression of antrum and hypothalamus was decreased in the ARE group by immunohistochemical detection; the results of semiquantitative reverse transcription polymerase chain reaction (RT-PCR) indicate that ARE inhibits the mRNA expression of VIP. Our results suggest that ARE can recover gastrointestinal hormone levels and regulation of the peripheral and central nervous system and alter gut peptide levels, which confirm the therapeutic effect of ARE on functional dyspepsia., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Chun Wang et al.)

Objective: To analyze the effect of insufficient intake of vitamin D (VD) on sperm quality and male fertility and to discuss the mechanism of the effect. Methods: VD deficiency mice were fed with VD-deficient diet and light-sheltered. The sperm motility, morphology, ultrastructure, testicular pathology, sex hormones and fertility of normal and VD-deficient mice were analyzed to investigate the effects of VD deficiency on male reproduction. Results: Compared with the normal group, the mice with VD deficiency had lower sperm concentration[(128±53) ×10(6)/ml vs( 58±15) ×10(6)/ml, P <0.05], less sperm in the epididymis, slightly less mature spermatozoa.The serum testosterone[(328±65 )nmol/L vs(255±58 )nmol/L]and estradiol levels[(60±115) pmol/L vs(384±104) pmol/L]were significantly lower ( P <0.05), and the FSH[(296±177)ng/L vs(219±105 )ng/L]and LH[(393±129) ng/L vs(364±108) ng/L]levels were significantly higher ( P <0.05). The other tests did not show any significant difference ( P >0.05). Conclusion: The impact of insufficient intake of VD on sperm quality is not prominent, the specific impact of VD on male reproductive needs to be further studied.

Objective: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection., Methods: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects., Results: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ［350/662］ vs 16.00% ［4/25］, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05)., Conclusions: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.

Aim: The mechanisms underlying the inhibitory effects of oxytocin (OT) on colon tone are not totally understood. We explore the mechanisms of OT on spontaneous contractility in rat distal colon and identify the mediators involved in this action., Methods: In rat distal colon strips, mechanical activity was analysed and the production of nitric oxide (NO) in tissue loaded with the fluorochrome DAF-FM was visualized by confocal microscopy. OT receptor (OTR) expression was determined by Western blotting and immunofluorescence., Results: In rat distal colon, OT produced a concentration-dependent reduction in the spontaneous contraction, which was abolished by the OTR antagonist atosiban, the neural blocker tetrodotoxin and the inhibitor of neuronal nitric oxide synthase (nNOS) NPLA. The inhibitory effects of OT were not affected by propranolol, atropine, the nicotinic cholinoceptor blocker hexamethonium, the vasoactive intestinal peptide receptor antagonist VIPHyb, the P 2 purinoceptor antagonist PPADS, the adenosine A1 receptors antagonist DPCPX and the prostacyclin receptor antagonist Ro1138452. The soluble guanylyl cyclase (sGC) inhibitor ODQ and the small conductance Ca 2+ -activated K + ( Ca K + ) channels blocker apamin significantly reduced the relaxation induced by OT, nicotine, sodium nitroprusside and the sGC activator BAY 41-2272. The neural release of NO elicited by OT was prevented by NPLA, tetrodotoxin and atosiban. The presence of the OTR and its co-localization with nNOS was detected by immunohistochemistry and Western blotting experiments., Conclusion: These results demonstrate the NO release from enteric neurones induced by activation of OTR mediates distal colon relaxation. sGC and small conductance Ca K + channels are involved in this relaxation., (© 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

Objective: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality., Methods: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the age of the patients., Results: A significant consistency was found in the SDF index (DFI) between the two methods (P<0.01). The DFI was correlated negatively with sperm motility, the percentage of progressively motile sperm, and that of morphologically normal sperm (P <0.01), but positively with the teratozoospermia index (P <0.01 in SCSA and P <0.05 in SCD). The DFI measured by SCSA showed a significantly positive correlation with the patients' age (P <0.01), but not that obtained by SCD., Conclusions: The results of both SCSA and SCD play an important role in predicting sperm quality. As a clinical index, the DFI has a predictive value for male infertility. However, the results of different detecting methods vary widely, which calls for further studies on their standardization.

The self-renewal and differentiation of hematopoietic stem cells (HSCs) in bone marrow are essential to replenish all blood cell types, but how this process is influenced by diet remains largely unclear. Here we show that a diet rich in fish oils promotes self-renewal of HSCs and extramedullary hematopoiesis. Chronic intake of a fish oil-rich diet increases the abundance of HSCs, alters the hematopoietic microenvironment, and, intriguingly, induces the expression of matrix metalloproteinase 12 (MMP12) in the bone marrow. Pointing to a direct effect of fish oil on MMP12 expression, omega-3 polyunsaturated fatty acids induce the expression of MMP12 in a dose-dependent manner in bone marrow cells. Importantly, down-regulation of MMP12 activity using an MMP12-specific inhibitor attenuates diet-induced myelopoiesis in both bone marrow and spleen. Thus, a fish oil-rich diet promotes hematopoiesis in the bone marrow and spleen, in part via the activity of MMP12. Taken together, these data provide new insights into diet-mediated regulation of hematopoiesis.

Background: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma., Methods: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR) was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups., Results: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification). Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis., Conclusion: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer., (© 2013 S. Karger AG, Basel)

The interleukin (IL)-1β-processing inflammasome has recently been identified as a target for pathogenic evasion of the inflammatory response by a number of bacteria and viruses. We postulated that the periodontal pathogen, Porphyromonas gingivalis may suppress the inflammasome as a mechanism for its low immunogenicity and pathogenic synergy with other, more highly immunogenic periodontal bacteria. Our results show that P. gingivalis lacks signaling capability for the activation of the inflammasome in mouse macrophages. Furthermore, P. gingivalis can suppress inflammasome activation by another periodontal bacterium, Fusobacterium nucleatum. This repression affects IL-1β processing, as well as other inflammasome-mediated processes, including IL-18 processing and cell death, in both human and mouse macrophages. F. nucleatum activates IL-1β processing through the Nlrp3 inflammasome; however, P. gingivalis repression is not mediated through reduced levels of inflammasome components. P. gingivalis can repress Nlrp3 inflammasome activation by Escherichia coli, and by danger-associated molecular patterns and pattern-associated molecular patterns that mediate activation through endocytosis. However, P. gingivalis does not suppress Nlrp3 inflammasome activation by ATP or nigericin. This suggests that P. gingivalis may preferentially suppress endocytic pathways toward inflammasome activation. To directly test whether P. gingivalis infection affects endocytosis, we assessed the uptake of fluorescent particles in the presence or absence of P. gingivalis. Our results show that P. gingivalis limits both the number of cells taking up beads and the number of beads taken up for bead-positive cells. These results provide a novel mechanism of pathogen-mediated inflammasome inhibition through the suppression of endocytosis.

In the title mol-ecular salt, 2C(6)H(11)NH(3) (+)·C(8)H(4)O(4) (2-), the terephthalate dianion is close to being planar (r.m.s. deviation = 0.049 Å). In the crystal, the cations and anions are linked by N-H⋯O hydrogen bonds into (010) sheets. Of the four terephthalate O atoms, two accept two hydrogen bonds each and two accept one hydrogen bond each.

The title compound, C(7)H(14)NO(+)·Br(-), was formed by reaction of 4-allyl-morpholine and hydrogen bromide. In the crystal, mol-ecules are connected via N-H⋯Br and C-H⋯Br hydrogen bonds, forming a three-dimensional network.

ASC/PYCARD is a common adaptor for a diverse set of inflammasomes that activate caspase-1, most prominently the NLR-based inflammasome. Mounting evidence indicates that ASC and these NLRs also elicit non-overlapping functions, but the molecular basis for this difference is unclear. To address this, we performed microarray and network analysis of ASC shRNA knockdown cells. In pathogen-infected cells, an ASC-dependent interactome is centered on the mitogen-activated protein kinase (MAPK) ERK and on multiple chemokines. ASC did not affect the expression of MAPK but affected its phosphorylation by pathogens and Toll-like receptor agonists via suppression of the dual-specificity phosphatase, DUSP10/MKP5. Chemokine induction, DUSP function, and MAPK phosphorylation were independent of caspase-1 and IL-1β. MAPK activation by pathogen was abrogated in Asc(-/-) but not Nlrp3(-/-), Nlrc4(-/-), or Casp1(-/-) macrophages. These results demonstrate a function for ASC that is distinct from the inflammasome in modulating MAPK activity and chemokine expression and further identify DUSP10 as a novel ASC target.

High-fat diet (HFD) and inflammation are key contributors to insulin resistance and type 2 diabetes (T2D). Interleukin (IL)-1β plays a role in insulin resistance, yet how IL-1β is induced by the fatty acids in an HFD, and how this alters insulin signaling, is unclear. We show that the saturated fatty acid palmitate, but not unsaturated oleate, induces the activation of the NLRP3-ASC inflammasome, causing caspase-1, IL-1β and IL-18 production. This pathway involves mitochondrial reactive oxygen species and the AMP-activated protein kinase and unc-51-like kinase-1 (ULK1) autophagy signaling cascade. Inflammasome activation in hematopoietic cells impairs insulin signaling in several target tissues to reduce glucose tolerance and insulin sensitivity. Furthermore, IL-1β affects insulin sensitivity through tumor necrosis factor-independent and dependent pathways. These findings provide insights into the association of inflammation, diet and T2D.

In the title compound, C(12)H(9)N(4)O(+)·C(7)H(5)O(2) (-), π-π stacking inter-actions [centroid-centroid distance = 3.6275 (14)  Å] stabilize the crystal structure. The dihedral angles between the central ring and the terminal rings are 3.27 (12) and 10.30 (13)°.

In the title compound, C(12)H(10)N(4)O(+)·2Br(-)·H(2)O, the cation is approximately planar: the terminal rings make a dihedral angle of 7.91 (6)° with each other and dihedral angles of 6.02 (1) and 6.50 (8)° with the central ring. It is linked to the bromide anions and water mol-ecules by N-H⋯Br hydrogen bonds. In addition, O-H⋯Br and N-H⋯Br hydrogen bonds link these units into a three-dimensional network. C-H⋯N, C-H⋯Br and N-H⋯O inter-actions are also observed.

Francisella tularensis is a facultative intracellular pathogen and potential biothreat agent. Evasion of the immune response contributes to the extraordinary virulence of this organism although the mechanism is unclear. Whereas wild-type strains induced low levels of cytokines, an F. tularensis ripA deletion mutant (LVSΔripA) provoked significant release of IL-1β, IL-18, and TNF-α by resting macrophages. IL-1β and IL-18 secretion was dependent on inflammasome components pyrin-caspase recruitment domain/apoptotic speck-containing protein with a caspase recruitment domain and caspase-1, and the TLR/IL-1R signaling molecule MyD88 was required for inflammatory cytokine synthesis. Complementation of LVSΔripA with a plasmid encoding ripA restored immune evasion. Similar findings were observed in a human monocytic line. The presence of ripA nearly eliminated activation of MAPKs including ERK1/2, JNK, and p38, and pharmacologic inhibitors of these three MAPKs reduced cytokine induction by LVSΔripA. Animals infected with LVSΔripA mounted a stronger IL-1β and TNF-α response than that of mice infected with wild-type live vaccine strain. This analysis revealed novel immune evasive mechanisms of F. tularensis.

In the title compound, C(2)H(5)N(2) (+)·BF(4) (-), the cations and anions are connected via inter-molecular N-H⋯F and C-H⋯F hydrogen bonds, forming a three-dimensional network.

In the title salt, C(8)H(14)N(2) (2+)·2Br(-), the cation has a crystallographically imposed centre of symmetry. The compound is isostructural with the chloride analogue. In the crystal structure, the cations and anions are connected via N-H⋯Br hydrogen bonds, forming layers parallel to the bc plane.

In the crystal structure of the title compound, C(6)H(9)N(2) (+)·C(6)H(4)NO(3) (-)·C(6)H(5)NO(3), ions and mol-ecules are connected via inter-molecular N-H⋯O, N-H⋯N, O-H⋯O and C-H⋯O hydrogen bonds into a three-dimensional network.

In the title compound, C(4)H(4)N(4)O, both H atoms bonded to one methyl-ene C atom are involved in C-H⋯N hydrogen-bonding inter-actions; one of the inter-actions results in dimers of the title mol-ecule lying about inversion centers in R(2) (2)(12) motifs and the other forms chains of mol-ecules lying along the c axis.

Objective: To compare the therapeutic effect of impacted high tibial osteotomy and conventional high tibial osteotomy for the treatment of flexional medial osteoarthritis of knee joint in aged patients., Methods: From July 2003 to July 2006, 30 patients with flexional medial knee osteoarthritis were treated with impacted high tibial osteotomy or conventional high tibial osteotomy randomly. All patients,aged from 60 to 82 years,were suffered from 7 degrees to 19 degrees knee flexion deformities and 3 to 20 years medical histories. The bone healing periods, the recover of flexion and inversion deformities, and the recover of the knee joint function were observed postoperatively. The patients were followed up at 4, 6, 8, 9, 10, 12 and 16 weeks, and 5, 7, 9 and 12 months postoperatively. The bone healing periods and the recover of flexional and inversion deformities were evaluated and compared. Twelve months postoperatively,the knee joint function were assessed with the Lysholm scoring criteria, and the therapeutic effects were compared between the two groups., Results: There was a significant difference in the average bone healing period between the impacted high tibial osteotomy group (9.26 +/- 2.23) weeks and the conventional high tibial osteotomy group (11.53 +/- 3.15) weeks. The knee joint function were evaluated according to the Lysholm clinical rating scales. One year postoperatively,the average Lysholm score were (88.5 +/- 4.4) points in the impacted high tibial osteotomy group,and the results showed excellent in 14 cases, good in 1. The average Lysholm score were (78.1 +/- 5.7) points in the conventional high tibial osteotomy group. The results showed 8 cases excellent, 5 good, 2 fair, accordingly. Postoperatively, the flexion deformities of the knee in the impacted high tibial osteotomy group were -1.1 degrees to 0 degrees and was corrected averagely (130 +/- 3.30) after surgery, and that in conventional high tibial osteotomy group (140 +/- 3.30) (the same as preoperation). The average postoperative femorotibial angle (FTA) were 170.2 degrees (ranged from 169.1 degrees to 172.3 degrees) and was corrected 12.3 degrees to 12.5 degrees after surgery in both groups., Conclusion: Compared with conventional high tibial osteotomy, impacted high tibial osteotomy can significantly shorten the bone healing period, improve the knee flexion, varus deformity, and the knee function.

Shortly after the cellular mechanism of RNA interference (RNAi) was first described, scientists began using this powerful technique to study gene function. This included designing better methods for the successful delivery of small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) into mammalian cells. While the simplest method for RNAi is the cytosolic delivery of siRNA oligonucleotides, this technique is limited to cells capable of transfection and is primarily utilized during transient in vitro studies. The introduction of shRNA into mammalian cells through infection with viral vectors allows for stable integration of shRNA and long-term knockdown of the targeted gene; however, several challenges exist with the implementation of this technology. Here we describe some well-tested protocols which should increase the chances of successful design, delivery, and assessment of gene knockdown by shRNA. We provide suggestions for designing shRNA targets and controls, a protocol for sequencing through the secondary structure of the shRNA hairpin structure, and protocols for packaging and delivery of shRNA lentiviral particles. Using real-time PCR and functional assays we demonstrate the successful knockdown of ASC, an inflammatory adaptor molecule. These studies demonstrate the practicality of including two shRNAs with different efficacies of knockdown to provide an additional level of control and to verify dose dependency of functional effects. Along with the methods described here, as new techniques and algorithms are designed in the future, shRNA is likely to include further promising application and continue to be a critical component of gene discovery.

Bacterial infection elicits a range of beneficial as well as detrimental host inflammatory responses. Key among these responses are macrophage/monocyte necrosis, release of the proinflammatory factor high-mobility group box 1 protein (HMGB1), and induction of the cytokine IL-1. Although the control of IL-1beta has been well studied, processes that control macrophage cell death and HMGB1 release in animals are poorly understood. This study uses Klebsiella pneumonia as a model organism because it elicits all three responses in vivo. The regulation of these responses is studied in the context of the inflammasome components NLRP3 and ASC, which are important for caspase-1 activation and IL-1beta release. Using a pulmonary infection model that reflects human infection, we show that K. pneumonia-induced mouse macrophage necrosis, HMGB1, and IL-1beta release are dependent on NLRP3 and ASC. K. pneumoniae infection of mice lacking Nlrp3 results in decreased lung inflammation and reduced survival relative to control, indicating the overall protective role of this gene. Macrophage/monocyte necrosis and HMGB1 release are controlled independently of caspase-1, suggesting that the former two responses are separable from inflammasome-associated functions. These results provide critical in vivo validation that the physiologic role of NLRP3 and ASC is not limited to inflammasome formation.

Neisseria gonorrhoeae is a common sexually transmitted pathogen that significantly impacts female fertility, neonatal health, and transmission of HIV worldwide. N. gonorrhoeae usually causes localized inflammation of the urethra and cervix by inducing production of IL-1beta and other inflammatory cytokines. Several NLR (nucleotide-binding domain, leucine-rich repeat) proteins are implicated in the formation of pro-IL-1beta-processing complexes called inflammasomes in response to pathogens. We demonstrate that NLRP3 (cryopyrin, NALP3) is the primary NLR required for IL-1beta/IL-18 secretion in response to N. gonorrhoeae in monocytes. We also show that N. gonorrhoeae infection promotes NLRP3-dependent monocytic cell death via pyronecrosis, a recently described pathway with morphological features of necrosis, including release of the strong inflammatory mediator HMBG1. Additionally, N. gonorrhoeae activates the cysteine protease cathepsin B as measured by the breakdown of a cathepsin B substrate. Inhibition of cathepsin B shows that this protease is an apical controlling step in the downstream activities of NLRP3 including IL-1beta production, pyronecrosis, and HMGB1 release. Nonpathogenic Neisseria strains (Neisseria cinerea and Neisseria flavescens) do not activate NLRP3 as robustly as N. gonorrhoeae. Conditioned medium from N. gonorrhoeae contains factors capable of initiating the NLRP3-mediated signaling events. Isolated N. gonorrhoeae lipooligosaccharide, a known virulence factor from this bacterium that is elaborated from the bacterium in the form of outer membrane blebs, activates both NLRP3-induced IL-1beta secretion and pyronecrosis. Our findings indicate that activation of NLRP3-mediated inflammatory response pathways is an important venue associated with host response and pathogenesis of N. gonorrhoeae.

Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-supporting tissue and affects 10-20 million people in the U.S. alone. The oral pathogen Porphyromonas gingivalis causes inflammatory host response leading to periodontal and other secondary inflammatory diseases. To identify molecular components that control host response to P. gingivalis in humans, roles for the NLR (NBD-LRR) protein, NLRP3 (cryopyrin, NALP3), and its adaptor apoptotic speck protein containing a C-terminal caspase recruitment domain (ASC) were studied. P. gingivalis strain A7436 induces cell death in THP1 monocytic cells and in human primary peripheral blood macrophages. This process is ASC and NLRP3 dependent and can be replicated by P. gingivalis LPS and Escherichia coli. P. gingivalis-induced cell death is caspase and IL-1 independent and exhibits morphological features consistent with necrosis including loss of membrane integrity and release of cellular content. Intriguingly, P. gingivalis-induced cell death is accompanied by the formation of ASC aggregation specks, a process not previously described during microbial infection. ASC specks are observed in P. gingivalis-infected primary human mononuclear cells and are dependent on NLRP3. This work shows that P. gingivalis causes ASC- and NLRP3-dependent necrosis, accompanied by ASC speck formation.

Healing of the inner wall of the same preclotted knitted Dacron arterial prostheses was compared in the descending thoracic aorta (DTA) and the abdominal aorta (AA) of the same dog. Each of 16 dogs received this dual implantation with study periods of 4 weeks for five dogs, 8 weeks for five dogs, and 16 weeks for six dogs. Healing was studied with light microscopy, scanning electron microscopy, transmission electron microscopy, and immunocytochemistry identification. The outer capsule was firmly adherent to the Dacron framework of all grafts implanted in the DTA; advanced healing of the inner wall of all thoracic grafts was present by 4 weeks, nearly complete healing by 8 weeks, and complete healing by 16 weeks. In contrast, the outer capsule was either not attached or only loosely adherent to the Dacron framework in eight AA grafts (50%), and in these implants no healing of the inner wall occurred beyond the limited perianastomotic pannus zone. In the other eight implants in which the outer capsule was firmly adherent to the Dacron framework, healing was roughly comparable to that in the grafts implanted in the DTA. This study demonstrated that (1) DTA grafts heal faster and more completely than AA grafts, (2) healing and endothelialization are related to the tightness of the outer capsule, (3) there is a high incidence of loose tissue attachment in the AA, and (4) healing of aortic grafts is site specific.

From 1981 to 1991, 146 infants under 1 month of age underwent repair of aortic coarctation. Forty-two had isolated coarctation, 53 had associated ventricular septal defect, and 51 had complex cardiac defects. The principal mode of presentation was congestive heart failure. The mean age at operation was 10.6 days. The technique for repair was left subclavian artery flap angioplasty in 126, resection with end-to-end anastomosis in 14, and a variety of repairs in 6 patients. Concomitant pulmonary artery banding was performed in 62 patients. The overall hospital mortality rate was 11%, and there was a strong association with pre-existing renal failure. The mean aortic clamp time in survivors was 23.9 minutes; mean hospital stay was 13.4 days. Significant restenosis occurred in 16 patients (11%) with an incidence of 10% after subclavian artery flap angioplasty. Eleven patients have undergone reoperation, and 5 were managed successfully with balloon dilatation.

Since 1972, 17 patients have been surgically treated for double aortic arch at our institution. The procedure became necessary before 12 months of age in 11 patients and before 24 months in 16 patients. The major symptoms were respiratory distress, noisy breathing, and respiratory infections; four patients also had dysphagia. A high degree of clinical suspicion should warrant further investigation. Barium swallow and bronchoscopy were diagnostic and revealed extrinsic compression of the esophagus and trachea, respectively. Division of the anterior arch was performed in 16 patients; the right (posterior) arch was divided in the remaining patient. Kommerell's diverticulum was found in four patients and was resected in order to avoid recurrence of dysphagia by compression. A vascular suspension procedure was necessary in 13 patients to further release the trachea and esophagus. There was no mortality in this series, and symptomatic improvement was achieved in all patients. A degree of tracheomalacia may be responsible for some residual symptoms in four patients.

Between 1970 and 1988, 12 restrosternal esophageal substitutions using an ileocolic interposition were performed. The ages of the 12 children ranged from 2 to 6 years. In 11 children the esophageal strictures were secondary to ingestion of caustic liquid. All patients had failed esophageal dilation therapy. One death occurred on the 7th postoperative day following an episode of cardiac arrest at surgery. Early postoperative complications included three cervical ileoesophageal anastomotic leaks, which healed spontaneously. One patient had gastrointestinal bleeding 10 years postoperatively. This was controlled by antacid therapy without recurrence. Redundancy of the interpositioned ileocolic segment was observed in three children. All 11 surviving patients can eat a normal diet and have normal growth and development.

Mediastinal masses in children constitute a heterogeneous group of malignant and benign neoplasms. The majority of malignant tumors in our series of 188 children with a mediastinal mass were Hodgkin's and non-Hodgkin's lymphoma (87 patients) arising in the anterior and middle mediastinum. Ganglioneuroma (17) arising in the posterior mediastinum made up the bulk of benign tumors (52). Infants less than 2 yr old presented with symptoms of tracheal compression, whereas older children had fewer symptoms but a far greater likelihood of having a malignancy. In the assessment of patients with mediastinal tumors, the posteroanterior and lateral chest roentgenograms were most often diagnostic, and computed tomography of the chest provided the most information concerning preoperative resectability. The excellent survival of patients with stage I and II Hodgkin's disease reflects the radiosensitivity of the tumor; in our series of 33 patients, survival was not increased by radical resection. Unlike lymphomatous tumors, neurogenic masses should be completely excised. When initial exploration reveals unresectability, biopsy followed by radiation therapy and second-look excision of the tumor can be accomplished. In patients with primary mediastinal sarcomas, total resection should be carried out if possible. In our series, adjuvant radiation therapy or chemotherapy was effective in only 1 of 15 children with sarcoma. Surgical treatment of all mediastinal masses except lymphoma should be complete excision. In cases of suspected lymphoma, cervical or supraclavicular node biopsy can yield adequate tissue for diagnosis.

A child, 2 years old, male suffering from severe jaundice, melena, severe anemia and right upper abdominal mass was admitted into our hospital. Diagnosis of obstructive jaundice was made before operation. On exploration, a tumor mass was found in the pancreatic head, which involved the duodenum and distal common bile duct. Pancreaticoduodenectomy with one stage pancreaticojejunostomy, choledochojejunostomy and gastrojejunostomy was carried out. Postoperative pathology showed adenocarcinoma of the distal common bile duct invading the periampullary tissues of the duodenum and infiltrating, to a lesser extent, into the pancreatic head. Carcinoma arising from the distal common bile duct is rare in infancy and childhood. Radical resection should be attempted if possible. In general, the prognosis is poor in this tumor. No complication after operation occurred on this patient but close follow-up is necessary. Pathology related to this tumor is discussed with a review of literature.

During a 6-yr period, 57 children and young adults less than 21 yr of age underwent 111 thoracotomies for pulmonary metastatic osteogenic sarcoma. Follow-up after the initial thoracotomy averaged 36.8 no and ranged from 1 to 78 mo. Twenty-eight patients (49%) underwent more than one thoracotomy--the number of multiple thoracotomies averaged 2.9 and ranged from two to eight. Twenty-six of the 57 patients are currently alive, and 25 of these are free of disease. Median survival was 36 mo. Actuarial survival curves demonstrated a 5-yr survival of approximately 40%. Seventy-one percent of patients who had a tumor-free interval of greater than 1 yr are currently alive, compared with 39% of patients who had a tumor-free interval of less than 1 yr. Patients with disease confined to one lobe at the initial thoracotomy had a better survival (64%) than patients with diffuse or bilateral disease (41%). An aggressive surgical approach toward osteogenic sarcoma with pulmonary metastasis thus appears to be justified.