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Chang-Sheng Ma,1,2,* Ya-Ping Ma,1,3,* Bo Han,1,2,* Wan-Li Duan,1 Shu-Chen Meng,1 Min Bai,1 Hao Dong,1 Li-Ying Zhang,1 Meng-Yuan Duan,1,2 Jing Liu,1 Ai-Jun Deng,2 Mao-Tao He1,2 1Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China; 3Department of Pathology, The 942Hospital of the People’s Liberation Army Joint Logistic Support Force, Yinchuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mao-Tao He, Department of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong, People’s Republic of China, Tel +86-18209617186, Fax +86-0536-3081201, Email hemaotao@sdsmu.edu.cn Ai-Jun Deng, Department of Ophthalmology, Affiliated Hospital of Shandong Second Medical University, Weifang, People’s Republic of China, Email dengaijun@hotmail.comPurpose: Ischemic stroke is a refractory disease wherein the reperfusion injury caused by sudden restoration of blood supply is the main cause of increased mortality and disability. However, current therapeutic strategies for the inflammatory response induced by cerebral ischemia-reperfusion (I/R) injury are unsatisfactory. This study aimed to develop a functional nanoparticle (MM/ANPs) comprising apelin-13 (APNs) encapsulated in macrophage membranes (MM) modified with distearoyl phosphatidylethanolamine-polyethylene glycol-RVG29 (DSPE-PEG-RVG29) to achieve targeted therapy against ischemic stroke.Methods: MM were extracted from RAW264.7. PLGA was dissolved in dichloromethane, while Apelin-13 was dissolved in water, and CY5.5 was dissolved in dichloromethane. The precipitate was washed twice with ultrapure water and then resuspended in 10 mL to obtain an aqueous solution of PLGA nanoparticles. Subsequently, the cell membrane was evenly dispersed homogeneously and mixed with PLGA-COOH at a mass ratio of 1:1 for the hybrid ultrasound. DSPE-PEG-RVG29 was added and incubated for 1 h to obtain MM/ANPs.Results: In this study, we developed a functional nanoparticle delivery system (MM/ANPs) that utilizes macrophage membranes coated with DSPE-PEG-RVG29 peptide to efficiently deliver Apelin-13 to inflammatory areas using ischemic stroke therapy. MM/ANPs effectively cross the blood-brain barrier and selectively accumulate in ischemic and inflamed areas. In a mouse I/R injury model, these nanoparticles significantly improved neurological scores and reduced infarct volume. Apelin-13 is gradually released from the MM/ANPs, inhibiting NLRP3 inflammasome assembly by enhancing sirtuin 3 (SIRT3) activity, which suppresses the inflammatory response and pyroptosis. The positive regulation of SIRT3 further inhibits the NLRP3-mediated inflammation, showing the clinical potential of these nanoparticles for ischemic stroke treatment. The biocompatibility and safety of MM/ANPs were confirmed through in vitro cytotoxicity tests, blood-brain barrier permeability tests, biosafety evaluations, and blood compatibility studies.Conclusion: MM/ANPs offer a highly promising approach to achieve ischemic stroke-targeted therapy inhibiting NLRP3 inflammasome-mediated pyroptosis. Keywords: apelin-13, cerebral ischemia-reperfusion injury, macrophage membrane, ischemic stroke therapy, pyroptosis

Functional molecules derived from stereogenic phosphorus centers have important applications in the discovery of drugs and agrochemicals. They are also widely utilized as chiral ligands or organocatalysts for diverse asymmetric transformations. However, access to P-stereogenic motifs has always been regarded as a highly challenging yet desirable goal in organic synthesis. The development of general and practical methods for the stereoselective construction of synthetically versatile P(III)-stereogenic phosphines is particularly appealing but remains elusive. Herein, we describe a nickel-catalyzed asymmetric alkylation of primary phosphines with alkyl halides for the synthesis of P-stereogenic secondary phosphine-boranes with high enantioselectivity and broad substrate scope. The resulting optically active secondary phosphine-boranes allow for further stereospecific transformations, thereby establishing a modular and efficient platform for the diversity-oriented construction of P-stereogenic phosphine compounds.

Objective:  This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China., Study Design:  The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups., Results:  Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p  < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p  < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p  > 0.05)., Conclusion:  Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Purpose: Breast cancer poses a huge threat to the lives and health of women worldwide. However, drug resistance makes the treatment of breast cancer challenging. This study aims to investigate the effect of miR-141-3p on paclitaxel resistance and its underlying mechanisms in breast cancer. Methods: Using bioinformatics analysis and qRT-PCR to explore the potential molecule miR-141-3p. Specific binding of miR-141-3p to Keap1 was determined by using a dual luciferase reporter assay. qRT-PCR and Western blot were utilized to observe the expression of miR-141-3p, Keap1, Nrf2, SLC7A11 and GPX4. GSH/GSSG content, MDA content and JC-1 assays were used to observe the ferroptosis levels of breast cancer cells. CCK-8 assay was used to observe the cell viability of breast cancer cells. Tumor subcutaneous transplantation experiment was used to understand the effect of miR-141-3p on paclitaxel resistance in breast cancer in vivo . Results: In the present study, miR-141-3p was found to be highly expressed and associated with poor prognosis in breast cancer. miR-141-3p inhibited Keap1 expression, promoted Nrf2 expression, and facilitated paclitaxel resistance in breast cancer cells. Inhibition of miR-141-3p promoted Keap1 expression, inhibited Nrf2 and its downstream SLC7A11-GSH-GPX4 signaling pathway, as well as promoted ferroptosis in cancer cells, and inhibited paclitaxel and RSL3 resistance. ML385 blocks the effect of miR-141-3p on paclitaxel resistance and ferroptosis resistance in breast cancer cells. In vivo , miR-141-3p mimics promoted paclitaxel resistance, whereas miR-141-3p inhibitors inhibited paclitaxel resistance in breast cancer cells. Conclusion: This work revealed that modulation of the Keap1-Nrf2 signaling pathway by miR-141-3p promoted paclitaxel resistance via regulating ferroptosis in breast cancer cells., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process of ischemic stroke is complex, and it is crucial to elucidate its molecular mechanisms and explore potential protective drugs. Ferroptosis, a newly recognized form of programmed cell death distinct from necrosis, apoptosis, and autophagy, is closely associated with the pathophysiology of ischemic stroke. N6022, a selective inhibitor of S-nitrosoglutathione reductase (GSNOR), is a "first-in-class" drug for asthma with potential therapeutic applications. However, it remains unclear whether N6022 exerts protective effects in ischemic stroke, and the precise mechanisms of its action are unknown. This study aimed to investigate whether N6022 mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis and to elucidate the underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) cell model and a middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model to mimic cerebral I/R injury. Our data, both in vitro and in vivo, demonstrated that N6022 effectively protected against I/R-induced brain damage and neurological deficits in mice, as well as OGD/R-induced BV2 cell damage. Mechanistically, N6022 promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity of SLC7A11-GPX4 system. Furthermore, N6022 interfered with the interaction of GSNOR with GSTP1, thereby boosting the antioxidant capacity of GSTP1 and attenuating ferroptosis. These findings provide novel insights, showing that N6022 attenuates microglial ferroptosis induced by cerebral I/R injury through the promotion of Nrf2 nuclear translocation and inhibition of the GSNOR/GSTP1 axis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ischemic stroke poses a major threat to human health. Therefore, the molecular mechanisms of cerebral ischemia/reperfusion injury (CIRI) need to be further clarified, and the associated treatment approaches require exploration. The NOD‑like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome serves an important role in causing CIRI, and its activation exacerbates the underlying injury. Activation of the NLRP3 inflammasome triggers the maturation and production of the inflammatory molecules IL‑1β and IL‑18, as well as gasdermin‑D‑mediated pyroptosis and CIRI damage. Thus, the NLRP3 inflammasome may be a viable target for the treatment of CIRI. In the present review, the mechanisms of the NLRP3 inflammasome in the intense inflammatory response and pyroptosis induced by CIRI are discussed, and the therapeutic strategies that target the NLRP3‑mediated inflammatory response and pyroptosis in CIRI are summarized. At present, certain drugs have already been studied, highlighting future therapeutic perspectives.

This study focused on the design and synthesis of two Cu-based coordination polymers, [Cu 2 (4-dpye)(5-HSIP)(μ 3 -O)(H 2 O) 2 ]·3H 2 O (Cu-CP-1) and [Cu(4-dpye) 0.5 (BCA) 2 ] (Cu-CP-2), where 4-dpye = N , N '-bis(4-pyridinecarboxamide)-1,2-ethane, 5-H 3 SIP = 5-sulfoisophthalic acid, and HBCA = benzoic acid, by using a hydrothermal method. Single-crystal X-ray diffraction (SCXRD) study revealed that by adding various auxiliary ligands, the architectures of the Cu-CPs could be altered, yielding two distinct multinuclear Cu clusters. Moreover, the Cu-CPs can be used as urease inhibitors (UIs). In vitro experiments showed that the Cu-CPs had good urease inhibition effects with IC 50 values of 0.53 ± 0.01 μM for Cu-CP-1 and 1.44 ± 0.01 μM for Cu-CP-2 and 98.48% (Cu-CP-1) and 96.27% (Cu-CP-2) inhibition of urease was achieved at a concentration of 100 μM, respectively. Furthermore, the inhibition effect of the tetranuclear Cu-CP was better than that of the binuclear Cu-CP. To better understand the potential mechanism of inhibition of the two copper complexes, we performed kinetic analysis using Lineweaver-Burk (L-B) plots in the presence of different concentrations of urea and different concentrations of inhibitors, and both Cu-CP-1 and Cu-CP-2 showed a non-competitive mode of inhibition. In addition, molecular docking analysis showed that the Cu-CPs were able to enter well into the urease binding pocket, thus interacting with key amino acid residues of urease to different degrees. Both kinetic and molecular docking studies theoretically explain and demonstrate the inhibition effect of both Cu-CPs on urease activity in vitro , which is expected to provide reasonable guidance and effective strategies for the development of novel, efficient, stable and safe CP-based UIs.

Catalytic asymmetric methods for the synthesis of synthetically versatile P-stereogenic building blocks offer an efficient and practical approach for the diversity-oriented preparation of P-chiral phosphorus compounds. Herein, we report the first nickel-catalyzed synthesis of P-stereogenic secondary aminophosphine-boranes by the asymmetric addition of primary phosphines to azo compounds. We further demonstrate that the P-H and P-N bonds on these phosphanyl hydrazine building blocks can be reacted sequentially and stereospecifically to access various P-stereogenic compounds with structural diversity., (© 2023 Wiley-VCH GmbH.)

Urease inhibitors (UIs) and nitrification inhibitors (NIs) can greatly reduce nitrogen loss in agriculture soil. However, design and synthesis of an efficient and environmentally friendly dual-functional inhibitor is still a great challenge. Herein, four metal-organic salts (MOSs) based on heterogeneous conformations of the ligand N 1 , N 1 , N 2 , N 2 -tetrakis(2-fluorobenzyl)ethane-1,2-diamine (L), namely, [2H L ] 2+ ·[MCl 4 ] 2- (M = Cu, Zn, Cd, and Co), have been synthesized by the "second sphere" coordination method and structurally characterized in detail. Single crystal X-ray diffraction (SCXRD) analyses reveal that the four MOSs are 0D supramolecular structures containing [2H L ] 2+ and [MCl 4 ] 2- , which are connected through non-covalent bonds. Furthermore, the urease and nitrification inhibitory activities of MOSs are evaluated, showing excellent nitrification inhibitory activity with the nitrification inhibitory rate as high as 70.57% on the 28 th day in soil cultivation experiment. In particular, MOS 1 shows significant urease inhibitory activity with half maximal inhibitory concentration (IC 50 ) values of 0.89 ± 0.01 μM (0.5 h) and 1.87 ± 0.01 μM (3 h), which can serve as a dual-functional inhibitor.

The efficient heterogeneous photo-Fenton-like catalysts based on two secondary ligand-induced Cu(II) metal-organic frameworks (Cu-MOF-1 and Cu-MOF-2) were constructed for the first time and investigated for the degradation of multiple antibiotics. Herein, two novel Cu-MOFs were prepared using mixed ligands by a facile hydrothermal method. The one-dimensional (1D) nanotube-like structure could be obtained by using V-shaped, long and rigid 4,4'-bis(3-pyridylformamide)diphenylether (3-padpe) ligand in Cu-MOF-1, while polynuclear Cu cluster could be prepared more easily by using short and small isonicotinic acid (HIA) ligand in Cu-MOF-2. Their photocatalytic performances were measured by degradation of multiple antibiotics in Fenton-like system. Comparatively, Cu-MOF-2 exhibited superior photo-Fenton-like performance under visible light irradiation. The outstanding catalytic performance of Cu-MOF-2 was ascribed to the tetranuclear Cu cluster configuration and excellent ability of photoinduced charge transfer and hole separation thus improved the photo-Fenton activity. In addition, Cu-MOF-2 showed high photo-Fenton activity in wide pH working range 3-10 and maintained wonderful stability after five cyclic experiments. The degradation intermediates and pathways were deeply studied. The main active species h + , O 2 - and OH worked together in photo-Fenton-like system and possible degradation mechanism was proposed. This study provided a new approach to design the Cu-based MOFs Fenton-like catalysts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Transition metal-catalyzed C-H bond functionalization is an important method in organic synthesis, but the development of methods that are lower cost and have a less environmental impact is desirable. Here, a Cu-catalyzed asymmetric C(sp 2 )-H arylation is reported. With diaryliodonium salts as arylating reagents, a range of ortho-arylated P-chiral phosphonic diamides were obtained in moderate to excellent yields with high enantioselectivities (up to 92% ee). Meanwhile, enantioselective C-3 arylation of diarylphosphine oxide indoles was also realized under similar conditions to construct axial chirality., (© 2023. The Author(s).)

A general and mild nickel-catalyzed enantioselective C(sp 2 )-P cross-coupling for synthesizing P-stereogenic phosphine oxides has been developed. The asymmetric alkenylation/arylation of racemic secondary phosphine oxides with alkenyl/aryl bromides generated P-stereogenic phosphine oxides with high yields and enantioselectivities. Various functional groups were tolerated, and the applications of this method were demonstrated through late-stage functionalization and product transformations., (© 2023 Wiley-VCH GmbH.)

A photoinduced copper-catalyzed C(sp 3 )-P bond formation has been developed by using N-(acyloxy)phthalimides as radical precursors and secondary phosphine boranes as coupling partners. A variety of alkyl carboxylic acid derivatives can be readily transformed into the corresponding phosphines with high reaction efficiency and structural diversity. Besides, utilizing the 1,5-HAT of the N-centered radical process, the δ C(sp 3 )-H bond can be coupled with secondary phosphines, which provides a novel method for the regioselective formation of C(sp 3 )-P bonds.

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy., (© 2023. The Author(s).)

An iridium-catalyzed asymmetric synthesis of branched allylic phosphine compounds under mild conditions is reported. Products bearing various functional groups can be synthesized with excellent stereoselectivity (up to 99.9 % ee) and regioselectivity. The employment of phosphine sulfides with relatively low deactivation capacity against metal catalysts is crucial for the success of this reaction., (© 2022 Wiley-VCH GmbH.)

Renal cancer displays a high metastatic potential and a poor response to chemotherapy. However, the critical contributors to renal cancer development remain elusive. This study focused on acetylcholine (ACh) signaling. We identified the vesicular acetylcholine transporter (SLC18A3) that upregulates in patients with renal cancer. We further discovered that SLC18A3 enhanced the uptake of ACh, a classical neurotransmitter mediating synaptic transmission. The elevated ACh activated the protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, which contributed to renal cancer cell proliferation and invasive migration. Consistently, SLC18A3 overexpression caused sustained tumor growth and increased lung metastases in A489-bearing mice. In summary, our study demonstrated that SLC18A3 contributed to cancer spread in an ACh/PKA/CREB-dependent manner, which may drive the design of efficacious treatment strategies., Competing Interests: None., (AJCR Copyright © 2022.)

The catalytic asymmetric synthesis of P-chiral phosphorus compounds is an important way to construct P-chiral ligands. Herein, we report a new strategy that adopts the pyridinyl moiety as the coordinating group in the cobalt-catalysed asymmetric nucleophilic addition/alkylation of secondary phosphine oxides. A series of tertiary phosphine oxides were generated with up to 99 % yield and 99.5 % ee, and with broad functional-group tolerance. Mechanistic studies reveal that (R)-secondary phosphine oxides preferentially interact with the cobalt catalysts to produce P-stereogenic compounds., (© 2021 Wiley-VCH GmbH.)

Objective: To investigate the prognostic value of infarct size (IS) in patients with acute ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Methods: A total of 104 patients with acute STEMI who underwent primary PCI treatment in Shengjing Hospital of China Medical University from February 2017 to November 2018 were included in the present study. All patients underwent cardiovascular magnetic resonance (CMR) within one week after primary PCI treatment. The subjects were followed up for two years. Major adverse cardiac events (MACE) included new onset congestive heart failure and/or recurrent nonfatal myocardial infarction and/orcardiac death. The optimal IS cutoff value for MACE was determined by receiver operating character (ROC) curve. Based on the IS cutoff value, the patients were divided into the high IS group and the low IS group. Clinical characteristics between the two groups were compared. A cox regression model was used to analyze the prognostic value of IS in acute STEMI patients treated with primary PCI for the adverse events. Results: The IS cutoff value determined by ROC curve was 13.55%. 50 patients were in the high IS group (IS≥13.55%) and 54 patients were in the low IS group (IS<13.55%). More female patients [14 cases (28.0%) vs. 6 cases (11.1%)] were in the IS group, and a higher proportion of patients in the high IS group had anterior myocardial infarction [27 cases (54.0%) vs . 16 cases (29.6%)] or microvascular obstruction [32 cases (64.0%) vs. 16 cases (29.6%)]. White blood cell counts [11.25(8.90, 13.38) ×10 9 /L vs. 9.25(7.58, 11.00) ×10 9 /L], troponin I levels [50.63(16.56, 76.30)μg/L vs. 16.58(2.66, 38.42)μg/L] and brain natriuretic peptide levels [178.10(79.70, 281.95)μg/L vs. 79.60(42.83, 183.90)μg/L] in the high IS group were higher than those in the low IS group ( P <0.05), and left ventricular ejection fraction [(45.15±10.65)% vs. (51.95±12.91)%] in the high IS group was lower than that in the low IS group ( P <0.05). Multivariate Cox regression analyses showed that IS was independently associated with the risk of cardiac death in patients with acute STEMI two years after primary PCI( P =0.033, HR =1.075, 95% CI 1.006-1.148). Every 1% increase in IS was associated with a 7.5% increase in cardiac death. Conclusions: Infarct size, measured by CMR within one week after primary PCI, is strongly associated with cardiac death in patients with acute STEMI two years after primary PCI. IS could be used as an index for the prognosis of patients with acute STEMI.

The first highly enantioselective catalytic synthesis of P-stereogenic secondary phosphine-boranes was realized by the asymmetric addition of primary phosphine to electron-deficient alkenes with a newly developed unsymmetric bisphosphine (PCP') pincer-nickel complex. Various P-stereogenic secondary phosphine-boranes were obtained in 57-92% yields with up to 99% ee and >20:1 dr. The follow-up alkylation upon P-C bond formation with alkyl halides provided a practical way to access P-chiral compounds with diverse functional groups.

Objective: To investigate the birth condition of preterm infants and the causes of preterm birth in Henan Province, China, and to provide a basis for the prevention and treatment of preterm birth., Methods: An epidemiological investigation was conducted for live-birth preterm infants who were born in 53 hospitals in 17 cities of Henan Province from January 1, 2019 to December 31, 2019 to investigate the incidence rate of preterm birth, the distribution of gestational age and birth weight, the use of antenatal glucocorticoids, and the causes of preterm birth., Results: The incidence rate of preterm birth was 5.84% (12 406/212 438) in the 53 hospitals. The proportions of preterm infants with gestational ages of < 28 weeks, 28 - < 32 weeks, 32 - < 34 weeks, and 34 - < 37 weeks were 1.58% (196/12 406), 11.46% (1 422/12 406), 15.18% (1 883/12 406), and 71.78% (8 905/12 406) respectively. The proportions of preterm infants with birth weights of < 1 000 g, 1 000- < 1 500 g, 1 500- < 2 500 g, 2 500- < 4 000 g, and ≥ 4 000 g were 1.95% (240/12 313), 8.54% (1 051/12 313), 49.53% (6 099/12 313), 39.59% (4 875/12 313), and 0.39% (48/12 313) respectively. The infants born by natural labor accounted for 28.76% (3 568/12 406), and those born by cesarean section accounted for 70.38% (8 731/12 406). The rate of use of antenatal glucocorticoids was 52.52% (6 293/11 983) for preterm infants and 68.69% (2 319/3 376) for the preterm infants with a gestational age of < 34 weeks. Iatrogenic preterm labor was the leading cause of preterm birth[40.06% (4 915/12 270)], followed by spontaneous preterm birth[30.16% (3 701/12 270)] and preterm birth due to premature rupture of membranes[29.78% (3 654/12 270)]. The top three causes of iatrogenic preterm birth were hypertensive disorders of pregnancy[47.12% (2 316/4 915)], fetal intrauterine distress[22.85% (1 123/4 915)], and placenta previa/placental abruption[18.07% (888/4 915)]., Conclusions: There is a relatively low incidence rate of preterm birth in Henan Province, and late preterm infants account for a relatively high proportion. Iatrogenic preterm birth is the main cause of preterm birth in Henan Province, and hypertensive disorders of pregnancy and fetal intrauterine distress are the main causes of iatrogenic preterm birth.

Pd-Catalyzed enantioselective C(sp3)-H arylation of N-(o-Br-aryl) anilides has been disclosed, and quaternary α-nitro amides were constructed with up to 98% ee. The presence of the nitro group on the substrate enables the progress of the reaction and the ready transformation of the product to optically active quaternary amino acid derivatives.

A strategy for the syntheses of benzofuranoquinolines and its analogues via the irradiation of o -phenylfuranyl/thienylpyridines/pyrimidines in DCM with UV light at rt under an argon atmosphere is described. The mechanism of this reaction through the process of 6π-electrocyclization, [1,5]-hydrogen shift, and 1,3-eneamine tautomerism leading to H 2 evolution was elucidated. Notably, the syntheses of cis -8b-methyl-8b,13a-dihydrobenzo[ f ]benzofuro[3,2- h ]quinolone via the photoinduced rearrangement of 2-(3-methylbenzofuran-2-yl)-3-phenylpyridine relevant to the mechanism of this reaction highlights the importance of the developed methodology.

Site-tunable functionalization of C(sp 3 )-H bonds has been accomplished through radical translocation and cross-coupling. Upon irradiation with visible light, copper-based photocatalyst [Cu(Xantphos)(dmp)]BF 4 enabled cross-coupling of N -alkoxyphthalimides with amino acid esters or amino acids to provide δ-C(sp 3 )-H alkylated alcohols (31 examples, up to 92% yield) with additive BNDHP or α-C(sp 3 )-H alkylated alcohols (18 examples, up to 86% yield) with additive DABCO in a highly regioselective fashion.

Objective: To investigate the risk factors for poor prognosis of neonatal bacterial meningitis., Methods: A retrospective analysis was performed for the clinical data of 152 children with neonatal bacterial meningitis. According to their prognosis, they were divided into a good prognosis group with 122 children and a poor prognosis group with 30 children. The two groups were compared in terms of general status, initial symptoms, and laboratory findings, and the risk factors for poor prognosis were analyzed., Results: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of children with a very low birth weight, a peripheral blood white blood cell count (WBC) of <5×10 9 /L or >20×10 9 /L, a C-reactive protein level of >50 mg/L, a cerebrospinal fluid (CSF) WBC of >500×10 6 /L, a CSF glucose level of <1 mmol/L, or a CSF protein level of >2 g/L, as well as significantly higher positive rates of blood culture and/or CSF culture, Gram-positive bacteria, and Streptococcus agalactiae (P<0.05). The multivariate logistic regression analysis showed that a CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L were independent risk factors for poor prognosis of neonatal bacterial meningitis., Conclusions: A CSF glucose level of <1 mmol/L and a CSF protein level of >2 g/L are risk factors for poor prognosis of neonatal bacterial meningitis.

A directing group-free, ligand-promoted palladium-catalyzed C-H arylation of internal alkynes with simple arenes was developed. Alkenyl chlorides resulting from a 1,4-chlorine migration or trisubstituted alkenes were produced in moderate to good yields depending on the type of alkyne., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Biomarkers are urgently required for predicting rejection so that anti-rejection treatment can be taken early to protect the allograft from irreversible damage. We hypothesized that the combination of circulating fractalkine, IFN-γ and IP-10 might serve as effective biomarkers for predicting early acute renal allograft rejection. We conducted a retrospective study of 87 subjects, who were classified into acute rejection group (ARG; n = 38) and non-rejection group (NRG; n = 49). Serum fractalkine, IFN-γ and IP-10 levels were measured by Luminex. The levels of fractalkine on day 0 and 7th day, IP-10 on 4th and 7th day, and IFN-γ on 7th day in ARG was significantly higher than that in NRG. Kaplan-Meier survival analysis highlighted the higher-levels groups of fractalkine on day 0, 4th and 7th day, IFN-γ on day 0, 1st, 4th, and 7th day and IP-10 on the 4th and 7th day in rejection-free survival probability were significantly lower than low-levels groups. ROC analyses highlight the superiority of fractalkine on day 0, IP-10 on day 0, 4th and 7th day, and IFN-γ on day 0, 1st and 7th day in prediction of acute rejection. We found the combination of fractalkine on day 0, IP-10 on 7th day and IFN-γ on 7th day had the highest AUC (0.866) for predicting rejection with a sensitivity of 86.8% and a specificity of 89.8%. Our findings demonstrated a more powerful prediction of early acute renal allograft rejection during the first month after transplantation by combination of multiple-biomarkers of fractalkine, IFN-γ and IP-10, and the results might help stratify the immunologic risk of acute allograft rejection in recipients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose To investigate the role of a tumor-penetrating peptide (internalizing CRGDRGPDC [iRGD])-integrated thermally sensitive liposomal (TSL) doxorubicin (DOX) in combination with radiofrequency (RF) ablation of liver tumors in an animal model. Materials and Methods Approval from the institutional animal care and use committee was obtained. Characterization of iRGD-TSL-DOX was performed in vitro. Next, H22 liver adenocarcinomas were implanted in 138 mice in vivo. The DOX accumulation and cell apoptosis of iRGD-TSL-DOX and TSL-DOX with or without RF were evaluated (n = 5) at different time points after treatment with quantitative analysis or pathologic staining. Mice bearing tumors were randomized into the following six groups (each group, eight mice): no treatment, iRGD-TSL-DOX, TSL-DOX, RF alone, RF ablation followed by TSL-DOX at 30 minutes (TSL-DOX combined with RF), and RF ablation followed by iRGD-TSL-DOX (iRGD-TSL-DOX combined with RF). Kaplan-Meier method was used to estimate the survival curves and log-rank test was used for comparison with statistical software. Results DOX encapsulation efficiency in iRGD-TSL-DOX was 97.5% ± 1.3 (standard deviation) with temperature-dependent drug release capability confirmed in vitro. In vivo, the iRGD-TSL-DOX group had overall higher DOX concentration in the tumor and had maximal difference at 24 hours compared with TSL-DOX group (2.7-fold). RF caused more intense cell apoptosis at 24 hours (median, 65% vs 21%, respectively; P < .001). For end-point survival, the iRGD-TSL-DOX combined with RF group had better survival (median, 32 days) than TSL-DOX combined with RF (median, 27 days; P = .035) or RF alone (median, 21 days; P < .001). Conclusion Conjugation to iRGD helped to improve intratumoral DOX accumulation and further enhanced the activity of TSL-DOX in RF ablation of liver tumors. © RSNA, 2017 Online supplemental material is available for this article.

Effect of time delay (τ) on intracellular calcium dynamics with non-Gaussian noises in transmission processes of intracellular Ca(2+) is studied by means of second-order stochastic Runge-Kutta type algorithm. By simulating and analyzing time series, normalized autocorrelation function, and characteristic correlation time of cytosolic and calcium store's Ca(2+) concentration, the results exhibit: (i) intracellular calcium dynamics's time coherence disappears and stability strengthens as τ → 0.1s; (ii) for the case of τ < 0.1s, the normalized autocorrelation functions of cytosolic and calcium store's Ca(2+) concentration show damped motion when τ is very short, but they trend to a level line as τ → 0.1s, and for the case of τ > 0.1s, they show different variation as τ increases, the former changes from underdamped motion to a level line, but the latter changes from damped motion to underdamped motion; and (iii) at the moderate value of time delay, reverse resonance occurs both in cytosol and calcium store.

In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro., (Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The present study aimed at investigating the possible effects of β-elemene on the progression of atherosclerosis in a rabbit model. The rabbit atherosclerosis model was established by the combination of balloon angioplasty-induced endothelial injury and an atherogenic diet fed to the rabbits. New Zealand White rabbits were randomly divided into four groups (8/group): the normal control group (fed with normal chow diet), and three experimental groups, placebo group, atorvastatin group, and β-elemene group (received the atherogenic diet). After two weeks on the diet, the three experimental groups underwent balloon injury at right common carotid artery and were treated with drugs or placebo for five weeks. Serum lipids were measured. Carotid artery lesions were isolated for histological and immunohistochemical analysis. In vitro, RAW264.7 macrophages were pretreated with β-elemene and ox-LDL for 24 h and the viability of macrophages was assayed using the MTT method. TNF-α and IL-6 were also determined. Compared with the control group, the thickness of the atherosclerosis lesion in the placebo group was significantly increased; The thickness the drug treatment groups were significantly decreased, compared with that of the placebo group. The infiltration of macrophage was markedly reduced in the β-elemene group compared with that of the placebo group. β-elemene treatment also reduced the levels of TC, TG, and LDL-C, compared with the placebo group. β-elemene decreased the TNF-α and IL-6 levels in vitro. In conclusion, our results demonstrated that β-elemene retarded the progression of atherosclerosis in vivo and in vitro, which may be related to the capacity of β-elemene to reduce the infiltration of macrophages and suppress inflammatory factors., (Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

A palladium-catalyzed enantioselective C-H arylation of N-(o-bromoaryl)-diarylphosphinic amides is described for the synthesis of phosphorus compounds bearing a P-stereogenic center. The method provides good enantioselectivities and high yields. The products were readily transformed into P-chiral biphenyl monophosphine ligands., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enantioselective arylation of secondary β-C(sp(3))-H bonds of 8-aminoquinoline amides was realized with a palladium catalyst. Chiral phosphoric amides and acids were used for the first time to control the stereoselectivity at the C-H bond cleavage step in the C-H activation reactions.

To explore the anti-atherosclerotic mechanism of estrogen and especially observe the effect of estradiol on the content of cholesterol in J774a.1 mouse mononuclear/macrophage-derived foam cells which were incubated with oxidized low-density lipoproteins (ox-LDL). J774a.1 mouse mononuclear/macrophages were incubated with ox-LDL or with both ox-LDL and estradiol (1, 0.1 or 0.01 micromol x L(-1)). Oil red O staining was used to observe the formation of foam cells, and cholesterol oxidase fluorometric was used to determine the content of cellular cholesterol content. Western blotting and RTFQ-PCR were used to observe the expressions of scavenger receptor class B type I (SR-B I ) in J774a.1 foam cells. Compared with the control cells, J774a.1 mouse mononuclear/macrophage-derived foam cells showed significantly increased contents of total cholesterol and cholesterol ester (P < 0.001) and decreased SR-B I mRNA expression (P < 0.01). Estradiol treatment significantly lowered the contents of total cholesterol and cholesterol ester (P < 0.05), and increased SR-B I protein and mRNA expression (P < 0.01) in the foam cells in a dose-dependent manner. Estradiol can inhibit the formation of mononuclear/macrophage-derived foam cells by decreasing the contents of total cholesterol and cholesterol ester and up-regulating the expression of SR-B I in the foam cells.

Background: Mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways are pleiotropic regulator of many genes involved in lipopolysaccharide (LPS)-induced acute lung injury (ALI). The present study aimed to reveal the protective effect of isotetrandrine (ITD), a small molecule inhibitor, on various aspects of LPS-induced inflammation in vitro and in vivo., Methods: In vitro, RAW 264.7 cells were pretreated with different dose of ITD 1 h before treatment with 1 mg/L of LPS. In vivo, to induce ALI, male BALB/c mice were injected intranasally with LPS and treated with ITD (20 and 40 mg/kg) 1 h before LPS., Results: In vitro, the cytokine levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in supernatant were reduced by ITD. Meanwhile, in vivo, pulmonary inflammatory cell infiltration, myeloperoxidase activity, total cells, neutrophils, macrophages, along with the levels of tumor necrosis factor-α, IL-1β, and IL-6 in bronchoalveolar lavage fluid were dose-dependently attenuated by ITD. Furthermore, our data showed that ITD significantly inhibited the activation of MAPK and NF-κB, which are induced by LPS in ALI model., Conclusions: These results suggested that ITD dose-dependently suppressed the severity of LPS-induced ALI by inactivation of MAPK and NF-κB, which may involve the inhibition of tissue oxidative injury and pulmonary inflammatory process., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Palladium-catalyzed asymmetric 1,6-addition of diarylphosphines to electron-deficient dienes was developed through rational selection of electron-withdrawing groups on the dienes. Various chiral allylic phosphine derivatives were synthesized in good yields with high enantioselectivity (up to 96% ee).

A series of bidentate monoanionic nitrogen ligands were designed and applied in the Pd-catalyzed oxidative Heck reaction of arenes with alkenes. Significant ligand-accelerated effects were observed, and direct C-H functionalized products were formed in high yields with meta-selectivity.

A Ag-mediated C-H/P-H functionalization reaction of arylphosphine oxides with internal alkynes was described for the direct preparation of benzo[b]phosphole oxides with a high yield. An unusual aryl migration on the P-atom derived from a C-P bond cleavage and a new C-P bond formation was also observed and demonstrated to proceed via the radical process.

Highly stereoselective addition of diarylphosphines to α,β-unsaturated sulfonic esters catalyzed through a PCP pincer-Pd complex is developed to synthesize chiral phosphine sulfonic esters with excellent enantioselectivity (up to 99.5% ee). The transformation of the chiral adduct into a useful palladium phosphine sulfonate complex is also demonstrated.

Background: Kidney injury molecule-1 (KIM-1) and osteopontin (OPN) play important roles in immune regulation. We hypothesized that serum KIM-1 and OPN might serve as biomarkers for predicting early acute rejection after kidney transplantation (KTx)., Methods: We conducted a single-center study of 155 subjects, who were classified into acute rejection group (ARG, n=32), non-rejection group (NRG, n=45) and healthy controls (HC, n=78). Serum KIM-1 and OPN levels were measured by Luminex., Results: The pre-transplant levels of serum KIM-1 and OPN in all KTx recipients were higher than those of HC (P<0.01). Compared with NRG, ARG showed significantly high serum levels of KIM-1 on day 0 (pre-KTx) and on the 1st, 4th, and 7th post-KTx days, and significantly high OPN levels on day 0 and the 7th day. Kaplan-Meier survival analysis showed that the higher levels of KIM-1 on day 0, the 1st and 4th days and OPN on day 0 and the 7th day were significantly associated with the lower probabilities of rejection-free survival. ROC analyses highlight the superiority of KIM-1 on the 1st day and OPN on the 7th day over those on other post-KTx days in prediction of acute rejection episodes. Multivariate logistic analysis revealed that the serum KIM-1 levels on the 1st post-KTx day and the OPN level on the 7th day were independent and powerful predictors of acute rejection episodes. An optimal predictive model was built by combining KIM-1 on the 1st day and OPN on the 7th day, and this model had the highest AUC (0.922)., Conclusions: This study was the first to demonstrate that serum KIM-1 and OPN may be the promising and elegant markers for prediction of early acute kidney allograft rejection., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

Background: Peripheral blood lymphocytes (PBL) of kidney transplant recipients stimulated in vitro release tumor necrosis factor (TNF)-α and interferon (IFN)-γ into the supernate as detected by a flow cytometric microcarrier assay (FCMA) that we used to predict acute rejection episodes., Methods: Fifty-two kidney transplant recipients were divided into 2 groups; stable function (STA; n = 30) and acute rejection (ARG; n = 22) for comparison with healthy volunteers (n = 10). PBL were stimulated for 8 hours with phorbol myphnistate acetate and ionomycin, thereafter detecting TNF-α and IFN-γ in culture supernates by FCMA. Receiver operating characteristics (ROC) procedures were used to assess the sensitivity and specificity to predict acute rejection., Results: The fluorescence intensity of TNF-α and IFN-γ in culture supernates was significant higher among healthy controls than STA: 68.38 ± 28.59 vs 51.08 ± 34.05, respectively (P < .05). The intensity of TNF-α and IFN-γ in ARG (144.47 ± 81.21 and 116.61 ± 53.89, respectively) was significant higher than STA (P < .001). The sensitivity and specificity to predict acute rejection were 86.4% and 86.7%, respectively, when analyzed by ROC curves combining TNF-α and IFN-γ. The intensity in noncultured plasma from ARG or STA was significant lower than that in culture supernates from ARG and STA with sensitivity and specificity to predict acute rejection episodes of 63.6% and 73.3%, respectively, when combining TNF-α and IFN-γ., Conclusions: Monitoring the expression of TNF-α and IFN-γ in cell culture supernates after stimulation of kidney transplant recipient PBL in vitro using FCMA predicted acute rejection episodes., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

Bis(phosphine) pincer-Pd complex-catalyzed asymmetric addition of diarylphosphines to N-tosylimines was developed for the synthesis of chiral phosphine sulfides with high stereoselectivities (up to 96% ee) under mild conditions.

A highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated aldehydes catalyzed by a bis(phosphine) pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 98% ee) under mild conditions. The application of the current method to the synthesis of enantiopure bisphosphine and its pincer-Pd complex has also been demonstrated., (© 2011 American Chemical Society)

Highly stereoselective asymmetric 1,4-addition of diarylphosphines to α,β-unsaturated N-acylpyrroles catalyzed by a PCP pincer-Pd complex has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (91-99% ee) under mild conditions. The products obtained can be further converted into chiral phosphine-oxazoline ligands.

The phytochemical study of the roots of Phlomis umbrosa Turcz afforded a new phenylethanoid glycoside, 3-hydroxy-4-methoxy-β-phenylethoxy-O-[2,3-diacetyl-α-l-rhamnopyranosyl-(1 → 3)]-4-O-cis-feruloyl-[β-d-apiofuranosyl-(1 → 6)]-β-d-glucopyranoside (1), and two new 28-noroleanane-derived spirocyclic triterpenoids, phlomishexaol C (2) and phlomishexaol D (3). Their structures were elucidated on the basis of 1D and 2D NMR analyses, in combination with high-resolution MS experiment.

An asymmetric addition of diarylphosphines to beta-substituted enones under mild conditions using a chiral pincer-palladium catalyst has been developed for the synthesis of chiral phosphines with excellent stereoselectivity (up to 99% ee).

Stable and reusable tetraorganosilicon reagents, alkenyl-, aryl-, and silyl[2-(hydroxymethyl)phenyl]dimethylsilanes, undergo 1,4-addition reactions to alpha,beta-unsaturated carbonyl acceptors under mild rhodium-catalysis. The reaction tolerates a diverse range of functional groups and is applicable to gram-scale synthesis. Use of a chiral diene ligand allows the achievement of the corresponding enantioselective transformations using the tetraorganosilicon reagents, providing the silicon-based approach to optically active ketones and substituted piperidones that serve as synthetic intermediates of pharmaceuticals. A rhodium alkoxide species is suggested to be responsible for a transmetalation step on the basis of the observed kinetic resolution of a racemic chiral phenylsilane in the enantioselective 1,4-addition reaction under the rhodium-chiral diene catalysis.

A full overview on the use of chiral phosphine-olefin ligands 1 in the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to alpha,beta-unsaturated carbonyl compounds is described. Effective chiral environment of a Rh/1 complex was shown to resemble that of a Rh/(R,R)-Ph-bod* complex by comparing the experimental results as well as the X-ray crystal structures. High catalytic activity of a Rh/1 complex was disclosed and the catalytic cycle involving a trimer-monomer equilibrium was established through mechanistic studies using a reaction calorimeter and (31)P NMR spectroscopy. A negative nonlinear effect derived from an inactive trimer-active monomer equilibrium of the catalyst was also successfully observed.

A rhodium/binap complex has been found to effectively catalyze the isomerization of unactivated internal alkynes to the corresponding 1,3-dienes in the presence of an azomethine imine as the reaction promoter.

A rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to substituted maleimides has been described. The regioselectivity in this reaction is controlled by the choice of ligand (dienes or bisphosphines), and 1,4-adducts with a quaternary stereocenter can be obtained with high regio- and enantioselectivity by the use of (R)-H8-binap.