[A clinical analysis of hypothyroidism in very low birth weight/extremely low birth weight infants].

OBJECTIVE: To study the risk factors and treatment outcome of hypothyroidism in very low birth weight/extremely low birth weight (VLBW/ELBW) infants. METHODS: The VLBW/ELBW infants who were diagnosed with hypothyroidism from September 2018 to December 2019 were enrolled as the case group (n=29). The children with normal thyroid function, matched at a ratio of 1 : 3, were enrolled as the control group (n=87). Clinical features were compared between the two groups. The correlation of thyroid function with gestational age and birth weight and the risk factors for hypothyroidism were analyzed. RESULTS: A total of 162 VLBW/ELBW infants who met the inclusion criteria were enrolled, with 29 infants in the case group (an incidence rate of hypothyroidism of 17.9%). The lower the birth weight, the higher the incidence rate of hypothyroidism (P<0.05). Triiodothyronine (T3) and free T3 were positively correlated with gestational age (P<0.05). T3 and free thyroxine were positively correlated with birth weight (P<0.05). Small for gestational age, multiple birth, maternal age ≥ 35 years, and use of dopamine were independent risk factors for hypothyroidism (P<0.05). In the case group, 16 infants were treated with levothyroxine (5-10 µg/kg daily), and the thyroid function returned to normal after 2 weeks of treatment. CONCLUSIONS: There is a high incidence rate of hypothyroidism in VLBW/ELBW infants. Small for gestational age, multiple birth, advanced maternal age, and use of dopamine are risk factors for hypothyroidism. The infants treated with levothyroxine should be followed up regularly to ensure an appropriate dose.

B-O-O-B Impurity Induces Ultralong Room-Temperature Phosphorescence of Boric Acid.

Organic materials that can emit ultralong room-temperature phosphorescence (RTP) have attracted a great deal of interest. Whether the pure boric acid (BA) solid can emit RTP and the origin of the RTP in BA caused a debate recently. Herein, our first-principles calculations and experimental measurements suggest that RTP of BA originates from the B-O-O-B group in a (H2BO3)2 species, which can be formed by polymerization of two dehydrogenated BA molecules under light irradiation. The calculated absorption, fluorescence, and phosphorescence spectra of B-O-O-B match well with the experiments. Experimental X-ray photoelectron and X-ray absorption spectra evidence the existence of B-O-O-B in BA. The O-O bond in B-O-O-B can break upon optical excitation, creating two B-O radicals. Radiative transition from localized dangling orbitals of the B-O radicals to the delocalized orbitals of the crystal bulk leads to the observed RTP. Our calculated phosphorescence lifetime is ∼1 s, which agrees well with the experiment.

Non-Noble-Metal-Doped Carbon Nitride Photocatalysts for Water Splitting Screened Out by Empty Defect States and the d-Band Center.

A rational design of water-splitting photocatalysts from the perspective of the electronic structure is highly desirable for optimizing catalytic activities. However, the structure-activity relationship is still unclear, which impedes the development of efficient catalysts. Herein, by comparing systematically the overall water-splitting capability of 20 kinds of metallic elements anchored at three sites (including cavity, carbon vacancy, and nitrogen vacancy) of graphitic carbon nitride (g-C3N4) through density functional theory calculations, we uncover that availability of in-gap empty defect states and the d-band center position are paramount parameters to determine activities of g-C3N4 on photocatalytic water splitting. In-gap empty states play a role in accommodating electrons from H2O to facilitate its splitting. A lower d-band center weakens the interaction between reaction intermediates and g-C3N4, thereby promoting O2 desorption. Metals embedded at carbon vacancies are found to be superior to those at cavities and nitrogen vacancies because the former not only provides ample in-gap empty states but also has a lower d-band center. We also discover a rule that, for a reaction in which the bond order between the metal and intermediate enlarges (reduces), its reaction difficulty increases (decreases) with the increasing atomic number for elements in the same period. After screening, we find that non-noble metals Co, Ni, and Ga anchored at carbon vacancies possess catalytic performances comparable to Pd- and Pt-doped systems, with the rate-determining barriers less than 0.55 eV. Our findings may provide useful information for designing effective photocatalysts.

Many-Body Green's Function Theory for Electronic Excitations in Complex Chemical Systems.

The GW method and the Bethe-Salpeter equation (BSE) have exhibited excellent performance in computing charged and neutral electronic excitations in materials of various dimensions in the past decades. Extensive benchmark studies have demonstrated that their precision can reach the level of high-level ab initio wave function approaches with a much lower computational cost. GW and BSE outperform the density functional theory because of both the more accurate electronic structures in GW and the capability to treat local, charge-transfer, and Rydberg excitations on the same footing in BSE. Presently, they are the only available first-principles approaches that can study electronic excitations at the surface and in the interior of periodic systems and at the interface between periodic systems with reliable accuracy. In this Perspective, a brief overview of GW and BSE and their applications in complex chemical systems is provided, with the goal of boosting their broader utilization in chemistry.

Crucial Role of Defect States in the Ultralong Phosphorescence of Organic Molecular Crystals.

Ultralong organic phosphorescence (UOP) in pure organic molecular crystals has attracted a lot of interest recently. There is much debate on the emission mechanism of this UOP. Two recent experimental works published in Nat. Photonics 2019, 13, 406-411 and Nat. Mater. 2021, 20, 175-180 attribute UOP in the 2,4,6-trimethoxy-1,3,5-triazine (TMOT) crystals and the carbazole crystals to H-aggregation of the TMOT molecules or the formation of charge-transfer excitons between the carbazole and impurity molecules. Our first-principles many-body Green's function theory calculations show that the lowest triplet states of these two crystals are in fact the localized defect states originating from the twisted TMOT molecules and the impurities, respectively. Energies of the H-aggregation-induced exciton and the charge-transfer exciton are too high to account for UOP. UOP should be mainly due to the little orbital overlap between the localized defect state and the delocalized band edges of the crystal. Strong intermolecular interactions suppress nonradiative decay of the triplet exciton localized on the defect.

[Relationship between the inserting sites of Fu's subcutaneous needling and traditional acupoints: revelation to acupuncture and moxibustion].

Focusing on the phenomenon of "de-acupoints" of the needle insertion sites in Fu's subcutaneous needling (FSN), the authors allocated the evolution and characteristics of the needle insertion sites of FSN. From six aspects, named morphology and structure, location, nomenclature, numbers and meridian tropism, indications and acupuncture manipulations, the comparison was made between the insertion sites of FSN and traditional acupoints. It is believed: ①The needle insertion sites of FSN has the basic attributes of acupoint, which not only refers to the operation site, but also indicates the reaction of disease; moreover, it is the treatment site with significant therapeutic effect. ②The optimized sites of insertion in FSN should be named differently and their locations and numbers should be specified relatively. ③The insertion sites of FSN should be further intersected and integrated with traditional acupoints, and a part of traditional acupoints should become the insertion sites of FSN. ④Accepting and integrating the insertion sites of FSN, and expanding the scope of traditional acupoints may be the new project in the research of traditional acupoints.

A nomogram for predicting death for infants born at a gestational age of <28 weeks: a population-based analysis in 18 neonatal intensive care units in northern China.

Background: In China, the number of preterm infants is the second largest globally. Compared with those in developed countries, the mortality rate and proportion of treatment abandonment for extremely preterm infants (EPIs) are higher in China. It would be valuable to conduct a multicenter study and develop predictive models for the mortality risk. This study aimed to identify a predictive model among EPIs who received complete care in northern China in recent years. Methods: This study included EPIs admitted to eighteen neonatal intensive care units (NICUs) within 72 hours of birth for receiving complete care in northern China between January 1, 2015, and December 31, 2018. Infants were randomly assigned into a training dataset and validation dataset with a ratio of 7:3. Univariate Cox regression analysis and multiple regression analysis were used to select the predictive factors and to construct the best-fitting model for predicting in-hospital mortality. A nomogram was plotted and the discrimination ability was tested by an area under the receiver operating characteristic curve (AUROC). The calibration ability was tested by a calibration curve along with the Hosmer-Lemeshow (HL) test. In addition, the clinical effectiveness was examined by decision curve analysis (DCA). Results: A total of 568 EPIs were included and divided into the training dataset and validation dataset. Seven variables [birth weight (BW), being inborn, chest compression in the delivery room (DR), severe respiratory distress syndrome, pulmonary hemorrhage, invasive mechanical ventilation, and shock] were selected to establish a predictive nomogram. The AUROC values for the training and validation datasets were 0.863 [95% confidence interval (CI): 0.813-0.914] and 0.886 (95% CI: 0.827-0.945), respectively. The calibration plots and HL test indicated satisfactory accuracy. The DCA demonstrated that positive net benefits were shown when the threshold was >0.6. Conclusions: A nomogram based on seven risk factors is developed in this study and might help clinicians identify EPIs with risk of poor prognoses early.

Development of an Aeromonas hydrophila recombinant extracellular protease vaccine.

Aeromonas hydrophila (Ah) exists widely in the aquatic environment and infects a variety of animals. Extracellular protease (EPR) is an important protective antigen that induces a specific antibody response to resist Ah infection. In this study, two genes encoding extracellular protease epr2 and epr3 were linked within the expression vector pET32a to construct a recombinant pET-epr2-3 plasmid. The immunogenicity of the fusion protein epr2-3 was investigated as a subunit vaccine in ICR mice. The recombinant epr2-3 protein induced the production of high antibody titers. The survival rate against homogenous Ah J-1 challenge was significantly higher in the epr2-3 vaccinated group (≥80%) compared with the inactivated Ah vaccinated group and the challenge control group (P < 0.01), thus indicating that the recombinant epr2-3 protein provided significant protection against Ah infection. Therefore, the recombinant epr2-3 is a promising candidate for development as a vaccine against Ah infections.

Activation of cardiac M3 muscarinic acetylcholine receptors has cardioprotective effects against ischaemia-induced arrhythmias.

Increasing evidence indicates the important roles of M(3) muscarinic acetylcholine receptors (M(3) mAChR) in the regulation and maintenance of cardiac function and heart disease. In the present study, we investigated whether the M(3) mAChR mediates the cardioprotection against ischaemia-induced arrhythmias and the mechanisms involved. Myocardial ischaemia was established in Wistar rats by occlusion of the left anterior descending coronary artery. Rats were treated with choline chloride (an M(3) mAChR agonist; 10 mg/kg, i.v.) 10 min before occlusion. In addition, 4-diphenylacetoxy-N-methylpiperidine-methiodide (4-DAMP; 0.12 µg/kg, i.v.) was administered 5 min before choline in the 4-DAMP-treated group. Ischaemia-induced arrhythmias were evaluated in each group for a period of 1 h after occlusion. After 24 h occlusion, protein and mRNA levels of L-type Ca(2+) channels and the Na(+) /Ca(2+) exchanger (NCX) were determined. Ischaemia-induced arrhythmias following coronary artery occlusion were diminished by choline and this effect was reversed in the 4-DAMP-treated group. In vitro, the effects of myocardial ischaemia were simulated by incubating isolated ventricular cardiomyocytes with Tyrode's solution (pH 6.8). Intracellular Ca(2+) overload was confirmed and this was decreased by choline. Furthermore, choline reduced the L-type Ca(2+) current (I(C) (a,) (L) ) compared with cardiomyocytes incubated in Tyrode's solution (pH 6.8) alone. Choline reduced the 'ischaemia'-induced upregulated expression of L-type Ca(2+) channels and NCX at both the protein and mRNA level. Based on these results, choline has an obvious protective effect against ischaemia-induced arrhythmias that is mediated via activation of cardiac M(3) mAChR, which reduces Ca(2+) overload mediated by L-type Ca(2+) channels and the NCX.

Attenuating effect of magnesium on pulmonary arterial calcification in rodent models of pulmonary hypertension.

OBJECTIVE: Vascular calcification has been considered as a potential therapeutic target in pulmonary hypertension. Mg2+ has a protective role against calcification. This study aimed to investigate whether Mg2+ could alleviate pulmonary hypertension by reducing medial calcification of pulmonary arteries. METHODS: Monocrotaline (MCT)-induced and chronic hypoxia-induced pulmonary hypertension rats were given an oral administration of 10% MgSO4 (10 ml/kg per day). Additionally, we administered Mg2+ in calcified pulmonary artery smooth muscle cells (PASMCs) after incubating with ß-glycerophosphate (ß-GP, 10 mmol/l). RESULTS: In vivo, MCT-induced and chronic hypoxia-induced pulmonary hypertension indexes, including right ventricular systolic pressure, right ventricular mass index, and arterial wall thickness, as well as Alizarin Red S (ARS) staining-visualized calcium deposition, high calcium levels, and osteochondrogenic differentiation in pulmonary arteries, were mitigated by dietary Mg2+ intake. In vitro, ß-GP-induced calcium-rich deposits stained by ARS, calcium content, as well as the detrimental effects of calcification to proliferation, migration, and resistance to apoptosis of PASMCs were alleviated by high Mg2+ but exacerbated by low Mg2+. Expression levels of mRNA and protein of ß-GP-induced osteochondrogenic markers, RUNX Family Transcription Factor 2, and Msh Homeobox 2 were decreased by high Mg2+ but increased by low Mg2+; however, Mg2+ did not affect ß-GP-induced expression of SRY-Box Transcription Factor 9. Moreover, mRNA expression and protein levels of ß-GP-reduced calcification inhibitor, Matrix GLA protein was increased by high Mg2+ but decreased by low Mg2+. CONCLUSION: Mg2+ supplement is a powerful strategy to treat pulmonary hypertension by mitigating pulmonary arterial calcification as the calcification triggered physiological and pathological changes to PASMCs.

[Therapeutic observation on horizontal penetration needling for residual dizziness after repositioning maneuver in patients with benign paroxysmal positional vertigo].

OBJECTIVE: To observe the effect of horizontal penetration needling at vertigo auditory area and balance area on residual dizziness after successful repositioning maneuver in patients with benign paroxysmal positional vertigo (BPPV). METHODS: Sixty-six patients with residual dizziness after successful repositioning maneuver for BPPV were randomly divided into an observation group (34 cases, 1 case dropped off) and a control group (32 cases, 2 cases dropped off). The patients in the observation group were treated with horizontal penetration needling at vertigo auditory area and balance area, once every other day; three times were taken as a course of treatment, and two courses of treatment were given. The patients in the control group received no acupuncture and medication. The dizziness handicap inventory (DHI) and visual analogue scale (VAS) scores were observed before treatment and after 1 and 2 courses of treatment. RESULTS: Except for the emotional score of DHI in the control group after 1 course of treatment, the sub item scores and total scores of DHI and VAS scores in the two groups after treatment were lower than those before treatment (P<0.01, P<0.05). After 1 and 2 courses of treatment, the function scores, emotion scores, total scores of DHI and VAS scores in the observation group were lower than those in the control group (P<0.01). CONCLUSION: Whether acupuncture or not, residual dizziness after repositioning maneuver for BPPV can be relieved within 2 weeks; horizontal penetration needling at vertigo auditory area and balance area could improve dizziness symptoms and shorten the course of disease.

Octreotide alleviates pancreatic damage caused by paraquat in rats by reducing inflammatory responses and oxidative stress.

This study explores the efficacy and mechanism by which octreotide (OCT) alleviates paraquat (PQ)-induced pancreatic injury. Twenty-four adult male rats were randomly divided into three groups: the normal control (NC), PQ poisoning, and OCT treatment groups. The PQ-induced pancreatic injury rat model was established by administering PQ (120 mg/kg). Treatment group rats received OCT (8 µg/kg body weight) every 8 h by subcutaneous injection, 1 h after PQ administration. Rats were euthanized 24 h after PQ injection. Serum amylase, lipase, tumor necrosis factor-α, and interleukin-6 levels were markedly increased in the PQ group versus the NC group. In pancreatic tissue, PQ poisoning drastically induced necrosis and increased inflammatory cytokine and oxidative stress marker levels. Compared with the PQ group, OCT reduced pancreatic damage and histological scores, serum amylase, lipase, and inflammatory cytokine levels, as well as oxidative stress. OCT demonstrates protective effects against PQ-induced pancreatic damage through anti-inflammatory and antioxidant actions.

Comprehensive circRNA expression profile and construction of circRNA-related ceRNA network in cardiac fibrosis.

Cardiac fibrosis is a common pathological condition that contributes to the progression of many cardiac diseases. Circular RNAs (circRNAs) are emerging as new regulators of cardiac fibrosis. However, the expression and function of circRNAs in cardiac fibrosis remain largely unknown. The present study aims to investigate the circRNA expression profile and identify the roles of circRNAs in cardiac fibrosis. Transforming growth factor-ß1 (TGF-ß1) was used to establish an in vitro model of cardiac fibrosis in cardiac fibroblasts. CircRNA sequencing revealed that a total of 283 circRNAs were aberrantly expressed in fibrotic cardiac fibroblasts, with 79 upregulated and 204 downregulated. The expression changes of randomly selected circRNAs were validated by real-time PCR. A circRNA-based competing endogenous RNA network 1755 nodes and 30394 edges was established, and module analysis was conducted using the plug-in MCODE. KEGG pathway enrichment analysis was performed for mRNAs involved in the top three enriched modules. The results showed that these mRNAs were enriched in cardiac fibrosis-related signalling pathways, including the 'TGF-beta signaling pathway', 'MAPK signaling pathway', 'AMPK signaling pathway', and 'PI3K-Akt signaling pathway'. The predicted ceRNAs and bioinformatics analysis revealed the potential role of circRNAs in cardiac fibrosis, which would provide useful information for understanding the mechanism and finding effective prevention and treatment targets for cardiac fibrosis.

A conjugated microporous polymer as a recyclable heterogeneous ligand for highly efficient regioselective hydrosilylation of allenes.

Pyridines containing adjacent C[triple bond, length as m-dash]C bonds were utilized as ligand units and integrated into the skeleton of conjugated microporous polymers. The resultant Pd-CMP-1 was first applied as a highly efficient heterogeneous catalytic system for Pd-catalyzed allene hydrosilylation towards a wide range of allenes to produce branched allylsilanes with high regioselectivity. The ligand units of the polymer, along with the confinement effect of the porous structure, jointly regulated the regioselectivity. The parts-per-million (ppm) levels of Pd, coordinated with the recyclable heterogeneous ligand, show promise for industrial applications. This work opens a new front of using CMP as an intriguing platform for developing highly efficient catalysts to control the regioselectivities in allene hydrosilylation.

Robot-assisted gallbladder-preserving hepatectomy for treating S5 hepatoblastoma in a child: A case report and review of the literature.

BACKGROUND: Hepatoblastoma (HB) is the most common hepatic malignant tumour in children, accounting for approximately 50%-60% of primary hepatic malignant tumours in children, mostly in children under 3 years old. In Western countries, the incidence of hepatoblastoma is approximately 1-2/100000. Da Vinci surgical system is fast becoming a key instrument in microinvasive surgery. The past decade has seen the rapid development of robot-assisted laparoscopy, which expends many fields including the liver surgery. This paper discusses the significance and feasibility of robot-assisted gallbladder-preserving hepatectomy for treating S5 hepatoblastoma in children. The aim of this essay is to compare the safety and effectiveness of robotic surgery with conventional laparoscopic surgery, and explore the meaning of preservation of the gallbladder by sharing this case. CASE SUMMARY: A 3-year-old child with a liver mass in the 5th segment was treated using the Da Vinci surgical system, and the gallbladder was retained. The child was admitted to the hospital for 20 d for the discovery of the right hepatic lobe mass. Ultrasonography revealed a low echo mass, 46 mm × 26 mm × 58 mm in size, indicating hepatoblastoma in the right lobe, and enhanced computed tomography showed continuous enhancement of iso-low-density lesions with different sizes and nodules and unclear boundaries, without the dilation of the intrahepatic bile duct, no enlargement of the gallbladder, and uniform thickness of the wall. The diagnosis was "liver mass, hepatoblastoma". It was decided to perform S5 liver tumour resection. During surgery, the tumour and gallbladder were isolated first, and the gallbladder could be completely separated from the tumour surface without obvious infiltration; therefore, the gallbladder was preserved. The cutting line was marked with an electric hook. The hepatic duodenal ligament was blocked with a urethral catheter using the Pringle method, and the tumour and part of the normal liver tissue were completely resected with an ultrasound knife along the incision. The hepatic portal interdiction time was approximately 25 min. An abdominal drainage tube was inserted. The auxiliary hole was connected to the lens, and the specimen was removed. The patient's status was uneventful, and the operation time was 166 min. The robotic time was 115 min, and the bleeding amount was approximately 200 mL. In total, 300 mL of red blood cell suspension and 200 mL of plasma were injected. No serious complications occurred. Pathological findings confirmed fetal hepatoblastoma and R0 resection. A gallbladder contraction test was performed two weeks after surgery. CONCLUSION: Robot-assisted S5 hepatectomy with gallbladder preservation is safe and feasible for specific patients.

Removal of pediatric stage IV neuroblastoma by robot-assisted laparoscopy: A case report and literature review.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an incidence of approximately 1/10000. Surgical resection is an effective treatment for children with NB. Robot-assisted laparoscopic surgery is a new method and is superior to conventional laparoscopic surgery, since it has been preliminarily applied in clinical practice with a significant curative effect. This paper discusses significance and feasibility of complete resection of stage IV NB using robot-assisted laparoscopic surgery, while comparing its safety and effectiveness with conventional laparoscopic surgery. CASE SUMMARY: In June 2018, a girl with stage IV retroperitoneal NB, aged 3 years and 5 mo, was admitted. Her weight was 15 kg, and her height was 100 cm. Robot-assisted, five-port laparoscopic resection of NB was performed. Starting from the middle point between the navel and the anterior superior iliac spine to the left lower abdomen, the pneumoperitoneum and observation hole (10 mm) were established using the Hasson technique. Operation arm #1 was located between the left anterior axillary line, the navel, and the costal margin (8 mm); operation arm #2 was located at the intersection of the right anterior axillary line and Pfannenstiel line (8 mm); one auxiliary hole was located between arm #2 (on the Pfannenstiel line) and the observation hole (12 mm); and another auxiliary hole (5 mm) was located slightly below the left side of the xiphoid. Along the right line of Toldt and the hepatic flexure of the transverse colon, the colon was turned to the left and below with a hook electrode. Through Kocher's incision, the duodenum and the pancreatic head were turned to the left to expose the inferior vena cava and the abdominal aorta. The vein was separated along the right external iliac, and the inferior vena cava was then lifted to expose the right renal vein from the bottom to the top. The tumor was transected horizontally below the renal vein, and it was first cut into pieces and then resected. The right renal artery and the left renal vein were also exposed, and the retrohepatic inferior vena cava was isolated. The tumor was resected along the surface of the psoas muscle, the back of the inferior vena cava, and the right side of the abdominal aorta. Finally, the lymph node metas-tases in front of the abdominal aorta and left renal vein were completely removed. The specimens were loaded into a disposable specimen retrieval bag and removed from the enlarged auxiliary hole. T-tube drainage was placed and brought out through a hole in the right lower quadrant of the abdomen. The operative time was 389 min, the time of pneumoperitoneum was 360 min, the intraoperative blood loss was approximately 200 mL, and the postoperative recovery was smooth. There were no complications, such as lymphatic fistula, diarrhea, bleeding, and paralytic ileus. Two months after discharge, there were no other complications. The literature on the application of robot-assisted laparoscopic surgery in the treatment of NB in children was reviewed. CONCLUSION: The robot has the advantages of a three-dimensional view and flexible operation, and it can operate finely along blood vessels. The successful experience of this case confirmed that robot-assisted laparoscopic surgery can skeletonize the abdominal blood vessels in the tumor and cut the tumor into pieces, indicating that robot-assisted laparoscopic surgery is feasible.

Role of the NOD1/NF-κB pathway on bovine neutrophil responses to crude lipopolysaccharide.

Cytosolic nucleotide oligomerisation domain (NOD)-like receptors play an important role in host defence against infection. Reduced NOD1 expression has been observed in dysfunctional neutrophils derived from periparturient cattle known to be most susceptible to coliform mastitis. However, whether impairment of NOD1 suppresses the immune responses of bovine neutrophils during bacterial infections remains unknown. Crude (phenol extracted) lipopolysaccharide (cLPS), which often contains other immunostimulatory molecules, including NOD1 agonist, is known to induce almost the whole bacterial response. This study was conducted to explore the role of NOD1/nuclear factor (NF)-κB pathway in the cytokine and functional responses of bovine neutrophils challenged with Escherichia coli-derived cLPS. Freshly isolated blood neutrophils from healthy heifers were pre-incubated for 2 h with ML130, a selective inhibitor of NOD1/NF-κB pathway. Cells were then exposed to cLPS for additional 4 h. Inhibition of the NOD1/NF-κB pathway resulted in a decrease in cLPS-induced phosphorylation of the inhibitor of NF-κBα (IκBα) in neutrophils. Impairment of the NOD1/NF-κB pathway tended to down-regulate mRNA levels of pro-inflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, chemokines IL-8 and C-X-C motif ligand 2 (CXCL2), and adhesion molecules CD11b and CD62L, in cLPS-challenged cells. Functional analyses showed that blocking the NOD1/NF-κB pathway inhibited neutrophil migration and phagocytic killing capacity, and promoted neutrophil death upon cLPS stimulation. The data presented here demonstrate that activation of NOD1/NF-κB pathway contributes to the functional responses of neutrophils to cLPS.

Synthesis of 5,6-Dihydropyrazolo[5,1-a]isoquinolines through Indium(III)-Promoted Halocyclizations of N-Propargylic Sulfonylhydrazones.

A novel method for the preparation of 5,6-dihydropyrazolo[5,1-a]isoquinoline via indium(III)-promoted halocyclizations of N-propargylic sulfonylhydrazones has been developed. The pyrazole and 3,4-dihydroisoquinoline moieties were synchronously formed via a cascade cyclization reaction using easily assembled open-chain compounds. The pyrazole and 3,4-dihydroisoquinoline moieties were formed via a cascade cyclization reaction using easily assembled open-chain compounds.

Effector responses of bovine blood neutrophils against Escherichia coli: Role of NOD1/NF-κB signalling pathway.

Neutrophils use a broad array of pattern recognition receptors to sense and respond to invading pathogens and are important in the early control of acute bacterial infections. Nucleotide-binding oligomerizing domain-1 (NOD1) is a cytoplasmic receptor involved in recognizing bacterial peptidoglycan. Reduced neutrophil NOD1 expression has been reported in periparturient dairy cows. The aim of this study was to investigate the role of NOD1 signalling in the early responses of bovine neutrophils to bacterial infections. Blood neutrophils from healthy heifers were preincubated for 2h with ML130, a selective inhibitor of NOD1-dependent nuclear factor-κB (NF-κB) activation. Thereafter, cells were cultured with live Escherichia coli for additional 30 min or subjected to Boyden chamber cell migration assay with E. coli in the lower chamber. Results showed that ML130 inhibited E. coli-induced NF-κB nuclear translocation. There was an indication, although not significant, that ML130 down-regulated gene expression of proinflammatory cytokines interleukin (IL)-1ß and tumour necrosis factor (TNF)-α, chemokines IL-8 and C-X-C motif ligand 2 (CXCL2), and adhesion molecule CD62L, in E. coli-challenged neutrophils. Flow cytometry-based Annexin V staining revealed a considerable increase in neutrophil survival upon E. coli infection, an effect that was attenuated in the presence of ML130. Additionally, inhibition of NOD1/NF-κB signalling resulted in reduced migration of neutrophils to E. coli, and impaired phagocytosis, intracellular bacterial killing and reactive oxygen species production by neutrophils. These results indicate that NOD1/NF-κB pathway plays a crucial role in modulating neutrophil responses that are important for early control of infections. Approaches aiming at restoring neutrophil NOD1 function could be beneficial for prevention or treatment of coliform mastitis.

Choline inhibits angiotensin II-induced cardiac hypertrophy by intracellular calcium signal and p38 MAPK pathway.

Choline, an agonist of M(3) muscarinic acetylcholine receptors, is a precursor and metabolite of acetylcholine and is also a functional modulator of cellular membrane. However, the effect of choline on cardiac hypertrophy is not fully understood. The present study was therefore designed to explore whether choline could prevent cardiac hypertrophy induced by angiotensin II (Ang II) and clarify its potential mechanisms. Cardiac hypertrophy was induced by 0.6 mg kg(-1) day(-1) Ang II for 2 weeks in the presence or absence of choline pretreatment, while cardiomyocyte hypertrophy was induced by Ang II 0.1 µM for 48 h. We found that choline pretreatment attenuated the increment cell size of cardiomyocytes induced by Ang II both in vivo and in vitro. The high ANP and ß-MHC levels induced by Ang II were also reversed by choline in cardiomyocytes. Meanwhile, choline pretreatment prevented the augment of reactive oxygen species (ROS) and intracellular calcium concentration in Ang II-treated cardiomyocytes. Furthermore, the upregulated phospho-p38 mitogen-activated protein kinase (MAPK) and calcineurin levels by Ang II in ventricular myocytes were attenuated by choline. In conclusion, choline prevents Ang II-induced cardiac hypertrophy through inhibition of ROS-mediated p38 MAPK activation as well as regulation of Ca(2+)-mediated calcineurin signal transduction pathway. Our results provide new insights into the pharmacological role of choline in cardiovascular diseases.