Gold Catalysis, Asymmetric Friedel-Crafts Alkylation Cascade for One-Pot Synthesis of Chiral Dihydrocarbazoles and Dihydrodibenzofurans.

A one-pot gold-catalyzed acyl migration followed by ytterbium-catalyzed asymmetric Friedel-Crafts alkylation is disclosed, leading to the rapid synthesis of chiral dihydrocarbazoles and dihydrodibenzofuran in generally moderate to good overall yields with good to excellent enantioselectivities. The gold-catalyzed acyl migration of propargyl acetates generates α-ylidene-ß-diketones with high E/Z ratios, which are then subjected to the ytterbium-catalyzed asymmetric Friedel-Crafts alkylation without any purification. Importantly, this protocol provides a new type of substrate for asymmetric Friedel-Crafts alkylation.

Attitudes and Barriers to Physical Activity and Exercise Self-Efficacy Among Chinese Pregnant Women: A Cross-Sectional Study.

Background: Most pregnant women do not reach the recommendation for physical activity (PA). As a subcategory of PA, exercise is also essential. Evidence on pregnant women's attitudes and barriers to PA and exercise self-efficacy in China is scarce. Aim: To explore the levels and influencing factors of attitudes and barriers to PA and exercise self-efficacy among pregnant women. Methods: A cross-sectional study of 311 pregnant women was conducted from August to December 2022. Individual characteristics, pregnant women's attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy were measured using the self-designed demographic questionnaire, pregnant women's attitudes toward exercise questionnaire, barriers to prenatal PA and exercise questionnaire, and the pregnancy exercise self-efficacy scale, respectively. Results: More than 90% of pregnant women believed exercise benefits themselves and their babies, and 40.8% of pregnant women did not know how to exercise. Women encounter different types of barriers to PA and exercise. Intrapersonal barriers included the proportion of feelings of tiredness (56.6%), low energy (54.7%), lack of interest or motivation (49.2%), feelings of illness and morning sickness (46.6%), and large body weight (43.7%). Interpersonal barriers included pregnant women being advised to avoid PA and exercise (49.2%), lack of clear advice about the intensity and dose of exercise (41.8%), no one to exercise with (38.9%), and lack of advice from healthcare professionals (38.6%). Weather conditions were the most significant environmental barriers (41.2%). The total score of pregnancy exercise self-efficacy was (38.50±7.33). Education level, parity, and attitudes toward exercise independently predict pregnant women's attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy, respectively. Conclusion: Pregnant women have a favorable attitude toward exercise and relatively good exercise self-efficacy but lack knowledge of exercise. They face numerous barriers. Medical professionals should encourage pregnant women with lower levels of education to exercise and assist multipara in overcoming obstacles.

Triplet Homoleptic Iridium(III) Complex as a Potential Donor Material for Organic Solar Cells.

Triplet photovoltaic materials have been rarely investigated in organic solar cells (OSCs) because the role and mechanism of triplet excitons are still unclear. Cyclometalated heavy metal complexes with triplet features are expected to increase exciton diffusion lengths and improve exciton dissociation in OSCs, while the power conversion efficiencies (PCEs) of their bulk-heterojunction (BHJ) OSCs are still limited to <4%. We herein report an octahedral homoleptic tris-Ir(III) complex TBz3Ir as a donor material for BHJ OSCs with a PCE of over 11%. In comparison with the planar organic TBz ligand and heteroleptic TBzIr, TBz3Ir demonstrates the highest PCE and best device stability in both fullerene- and non-fullerene-based devices, owing to the long triplet lifetime, enhanced optical absorption, increased charge transport, and improved film morphology. From transient absorption, triplet excitons were deduced to participate in the photoelectric conversion process. In particular, the more significant 3D structure of TBz3Ir induces an unusual film morphology in TBz3Ir:Y6 blends, showing obviously large domain sizes suitable for triplet excitons. Thus, a high PCE of 11.35% with a high circuit current density of 24.17 mA cm-2 and a fill factor of 0.63 is achieved for small-molecular Ir complex-based BHJ OSCs.

Circulating miR-342-5p serves as a diagnostic biomarker in patients with carotid artery stenosis and predicts the occurrence of the cerebral ischemic event.

BACKGROUND: Carotid artery stenosis (CAS) is an important risk factor for cerebral ischemia events (CIE). Previous studies have shown that microRNAs (miRNAs) are involved in the occurrence and development of CAS. AIMS: The purpose of this study was to reveal the clinical diagnostic value of miR-342-5p for asymptomatic CAS (ACAS) and to evaluate its predictive value for the occurrence of CIE in patients. METHODS: A total of 92 ACAS patients and 86 healthy controls were enrolled as subjects. The expression level of serum miR-342-5p was detected by qRT-PCR. The receiver operating characteristic (ROC) curve was used to detect the diagnostic value of miR-342-5p in ACAS. Kaplan-Meier survival and Cox regression analysis assessed the predictive value of miR-342-5p for the occurrence of CIE in ACAS patients. RESULTS: The level of serum miR-342-5p in ACAS patients was significantly higher than that in healthy controls (P < 0.05). ROC curve showed the high diagnostic value of serum miR-342-5p, which could distinguish ACAS patients from healthy controls. Multivariate Cox regression analysis confirmed that miR-342-5p was an independent predictor (HR = 5.512, 95%CI = 1.370-22.176, P = 0.016). What is more, Kaplan-Meier analysis confirmed that patients with high miR-342-5p expression develop more CIE (log-rank, P = 0.020). CONCLUSIONS: miR-342-5p was significantly overexpressed in ACAS. And the upregulation of serum miR-342-5p is a valuable diagnostic biomarker and can predict the occurrence of CIE.

Clinical value of miR-191-5p in predicting the neurological outcome after out-of-hospital cardiac arrest.

BACKGROUND: The diagnostic and prognostic value of microRNAs (miRNA) in human disease has been confirmed in a number of clinical studies. AIMS: The purpose of this study was to investigate the predictive value of miR-191-5p in the neurological outcome of patients recovering from out-of-hospital cardiac arrest (OHCA). METHODS: A total of 260 patients undergoing the target temperature management trial were analyzed. The expression level of serum miR-191-5p was detected by qRT-PCR at 48 h after return of spontaneous circulation (ROSC). ROC curve was established to evaluate the ability of miR-191-5p as a biomarker for predicting adverse neurological outcomes after OHCA. Kaplan-Meier curve and Cox regression analysis were used for survival analysis. RESULTS: One hundred eighteen patients (45%) had poor neurological outcomes at 6 months. The expression level of serum miR-191-5p in patients with poor neurological outcomes was significantly lower than that in patients with good neurological prognosis (P < 0.001) and was not associated with TTM trial. The AUC, sensitivity, and specificity of the ROC curve were 0.899, 84.7%, and 82.4%, respectively, suggesting that the level of miR-191-5p had the ability to predict neurological outcome. By the end of the experiment, 88 patients (34%) were dead. Results of survival analysis showed that lower miR-191-5p expression level was significantly associated with lower survival rate (HR: 0.344, 95% CI = 0.208-0.567, P < 0.001). CONCLUSIONS: The level of miR-191-5p was down-regulated in patients with poor neurological outcomes, and it could be used as a promising novel biomarker for prediction of neurological outcome and survival after OHCA.

Electrochemical phosphorylation of arenols and anilines leading to organophosphates and phosphoramidates.

A practical phosphorylation for generating organophosphates and phosphoramidates via electrochemical dehydrogenative cross-coupling of P(O)H compounds with arenols and anilines is disclosed. This method involves using inorganic iodide salts as both redox catalysts and electrolytes in an undivided cell without the addition of oxidants or bases. A preliminary mechanistic study suggests that radicals are not involved in this process. This method is green and eco-friendly and has good functional group tolerance, high yields and broad substrate scope, with the potential for practical synthesis.

[Genetic variant analysis of a neonate with Cornelia de Lange syndrome].

OBJECTIVE: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION: The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.

The diagnostic value of PIVKA-II, AFP, AFP-L3, CEA, and their combinations in primary and metastatic hepatocellular carcinoma.

BACKGROUND: Early diagnosis decreases the mortality of hepatocellular carcinoma (HCC). We aimed to investigate the usefulness of PIVKA-II, AFP, AFP-L3, CEA, and their combinations in the diagnosis of primary and metastatic HCC. METHODS: One hundred and twenty patients with primary HCC (PHC), 115 with metastatic HCC (MHC), 89 with chronic liver disease (CLD), and 116 healthy volunteers were included. The diagnostic values of each marker and their combinations for HCC diagnosis were represented by ROC curve analyses. RESULTS: PIVKA-II, AFP, and AFP-L3 levels in PHC group were higher than that in normal control, CLD, and MHC groups. CEA levels in MHC group were higher than that in the other three groups. When the four markers were analyzed individually, PIVKA-II showed the highest positive rate in PHC group (76.7%) and CEA showed the highest positive rate in MHC group (69.6%). PIVKA- II showed the largest area under ROC curve (AUC = 0.835) to discriminate PHC group from CLD group. Combined PIVKA-II with AFP-L3 increased the AUC to 0.910. CEA showed the highest AUC (0.849) to discriminate MHC group from CLD group. Combined CEA with PIVKA-II increased the AUC to 0.866. AFP-L3 alone showed the highest AUC (0.890) to discriminate MHC group from PHC group. Combined PIVKA-II with AFP-L3, and CEA increased the AUC to 0.957. CONCLUSION: PIVKA-II, AFP-L3, AFP, and CEA are effective biomarkers for the diagnosis of PHC and MHC. Their combinations could improve the diagnostic performance compared with each marker used alone in detecting PHC and MHC.

Heparin improves alveolarization and vascular development in hyperoxia-induced bronchopulmonary dysplasia by inhibiting neutrophil extracellular traps.

The objective of this study was to assess the role of NETs in BPD of hyperoxia-induced rat model and the effect of heparin on alveolarization and vascular development in BPD. The neonatal rats exposed to 90% oxygen continuously for 7 days to mimic BPD, meanwhile, the rats were injected by different doses of histones to evaluate the impact on lung injury. The newborn rats exposed to hyperoxia were injected by different doses of heparin (250 U/kg, 500 U/kg) or anti-H4 antibody to evaluate the effect of heparin. Histones and hyperoxia impaired alveolarization with the increase of mean linear intercept (MLI) and the decrease of radial alveolar count (RAC), decreased lung angiogenesis with the decrease expression of VEGF, and increased the expression of NETs, histones and pro-inflammatory factor. However, low dose heparin (250U/kg) administration enhanced survival, improved alveolarization and vascular development in hyperoxia-induced BPD, as well as reduced expression of NETs, histones and pro-inflammatory factor. We concluded that heparin improves alveolarization and vascularization in BPD by inhibiting NETs.

Dehydrocostus lactone suppresses ox-LDL-induced attachment of monocytes to endothelial cells.

Atherosclerosis is a cardiovascular disease that affects most people to at least some extent by old age. Many factors contribute to atherogenesis, and although it is extremely common, the mechanisms behind the pathogenesis of the disease remain poorly understood. Endothelial dysfunction is thought to be one of the main causes of atherosclerosis along with numerous other factors, such as oxidative stress and proinflammatory cytokine upregulation. The culmination of the complications that lead to atherogenesis is the formation of a fatty plaque on the intima of the arterial endothelium. In this study, we explore these aspects and others in regard to the treatment potential of dehydrocostus lactone (DHL), which is naturally occurring in certain flora such as the Saussurea lappa costus plant. Having long been used in traditional Chinese medicine, the effects of this plant are only just beginning to be studied by modern science. Among our most noteworthy findings are that DHL exerts an inhibitory effect against the increased expression of VCAM-1 and E-selectin induced by exposure to oxidized low-density lipoprotein (ox-LDL), which has been linked to the development and progression of atherosclerosis. The introduction of DHL also significantly diminished the downstream effects of VCAM-1 and E-selectin, such as the attachment of monocytes to the endothelium and the release of proinflammatory cytokines and chemokines, including TNF-α, MCP-1, and HMGB1. Furthermore, DHL is capable of rescuing the expression of KLF2, an important regulator of VCAM-1 and E-selectin expression. Together, our findings demonstrate the potential of DHL as a prophylactic or therapeutic treatment against ox-LDL-induced atherosclerosis via inhibition of the attachment of monocytes to endothelial cells.

Human ß-Defensin-2 Improves Hyperoxia-Induced Lung Structural and Functional Injury in Neonatal Rats.

BACKGROUND Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. ß-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. MATERIAL AND METHODS The neonatal rats were exposed to 90% oxygen (O2) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O2, in 90% O2 with null adenovirus vector infection (O2+Ad), and in 90% O2 with gene therapy through adenovirus transfected hBD2 (O2+Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. RESULTS The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1ß, IL-6, and TNF-alpha were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O2+Ad-hBD2 group. CONCLUSIONS In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1ß, IL-6, and TNF-alpha.

Immunogenicity of a Virus-Like-Particle Vaccine Containing Multiple Antigenic Epitopes of Toxoplasma gondii Against Acute and Chronic Toxoplasmosis in Mice.

There is no effective protective vaccine against human toxoplasmosis, which is a potential threat to nearly a third of the world population. Vaccines based on virus-like particles (VLPs) have been highly successful in humans for many years, but have rarely been applied against Toxoplasma gondii infection. In this study, we inserted a B cell epitope (SAG182-102 or SAG1301-320), a CD8+ cell epitope (HF10 or ROP7), and a CD4+ cell epitope (AS15) of T. gondii into a truncated HBcΔ(amino acids1-149) particle to construct four chimeric VLP vaccine formulations, i.e., HBcΔH82, HBcΔH301, HBcΔ R82, and HBcΔ R301. When these chimeric HBc particles were expressed in Escherichia coli, they showed icosahedral morphology similar to that of the original VLPs and were evaluated as vaccine formulations against acute and chronic toxoplasmosis in a mouse model (BALB/c mice (H-2d). All these chimeric HBc VLPs induced strong humoral and cellular immune responses with high IgG antibody titers and interferon(IFN)-γ production. Only the mice immunized with HBcΔH82 showed prolonged survival time (15.6 ± 3.8 vs. 5.6 ± 0.8 days) against acute infection with RH tachyzoites and decrease in brain parasite load (1,454 ± 239 vs. 2,091 ± 263) against chronic infection with Prugniuad cysts, as compared to the findings for the control group. These findings suggest that HBc VLPs would act as an effective carrier for delivering effective multiple antigenic epitopes and would be beneficial for developing a safe and long-acting vaccine against toxoplasmosis.

Clinical characteristics and effective treatments of scrub typhus-associated hemophagocytic lymphohistiocytosis in children.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon and life-threatening disorder that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus). Here, we describe the clinical features, laboratory parameters, management, and outcome of 16 children with scrub typhus-associated HLH. All patients satisfied the HLH-2004 diagnostic criteria. All patients had fever of unknown origin and multisystem damage. Raised hepatic transaminases and abnormalities in routine blood test were observed in all children. Imaging tests showed abnormalities in 10 cases. Six patients were treated with intravenous azithromycin for 5 days, and 10 with intravenous chloramphenicol for 7-10 days because of non-response to 3-day azithromycin treatment. Five patients were treated with intravenous albumin and 3 with intravenous immunoglobulin. Two patients with severe symptoms (shortness of breath, cyanosis) were treated with dexamethasone (0.3 mg/kg/d). Fifteen patients recovered completely after 8-22 days of treatment. One patient died. The occurrence of severe complications draws attention to the need for early diagnosis and effective treatment. Anti-rickettsial antibiotic treatment (azithromycin or chloramphenicol) without the need for chemotherapy may be beneficial in such cases, instead of treatment according to the 2004 HLH protocol.

One-pot synthesis of glycosyl phenylthiosulfonates from sulfinate, S and glycosyl bromides.

Glycosyl phenylthiosulfonates are reagents which are valuable for the S-glycosylation decoration of organic compounds and proteins. Here, one-pot multiple-component synthesis of glycosyl phenylthiosulfonates from sulfinate, sulfur powder and glycosyl bromides is reported. The reactions afford glycosyl phenylthiosulfonates in good yields under mild conditions. Further application and exploration of glycosyl phenylthiosulfonates are still on underway in our group.

Simultaneous Dual-mode Emission and Tunable Multicolor in the Time Domain from Lanthanide-doped Core-shell Microcrystals.

The dual-mode emission and multicolor outputs in the time domain from core-shell microcrystals are presented. The core-shell microcrystals, with NaYF4:Yb/Er as the core and NaYF4:Ce/Tb/Eu as the shell, were successfully fabricated by employing the hydrothermal method, which confines the activator ions into a separate region and minimizes the effect of surface quenching. The material is capable of both upconversion and downshifting emission, and their multicolor outputs in response to 980 nm near-infrared (NIR) excitation laser and 252 nm, and 395 nm ultraviolet (UV) excitation light have been investigated. Furthermore, the tunable color emissions by controlling the Tb3+- Eu3+ ratio in shells and the energy transfer of Ce3+→Tb3+→ Eu3+ were discussed in details. In addition, color tuning of core-shell-structured microrods from green to red region in the time domain could be obtained by setting suitable delay time. Due to downshifting multicolor outputs (time-resolved and pump-wavelength-induced downshifting) coupled with the upconversion mode, the core-shell microrods can be potentially applied to displays and high-level security.

Copper-catalyzed generation of flavone selenide and thioether derivatives using KSeCN and KSCN via C-H functionalization.

Flavone selenide or sulfur-containing derivatives are pretty valuable in drug discovery due to their diversity of important bioactivities. Here, two simple Cu-catalyzed methods of constructing C-Se and C-S bonds on flavone skeletal structures via C-H functionalization are reported, which regioselectively afford flavone selenide and sulfide derivatives in good yields using cheap KSeCN or KSCN salts as selenium and sulfur agents. These methods further enrich the current C-Se and C-S bond construction methods.

Spatially confined luminescence process in tip-modified heterogeneous-structured microrods for high-level anti-counterfeiting.

Recent years have witnessed the progress of lanthanide-doped materials from fundamental material synthesis to targeted practical applications such as optical applications in photodetection, anti-counterfeiting, volumetric display, optical communication, as well as biological imaging. The unique compositions and structures of well-designed lanthanide ion-doped materials could expand and strengthen their application performances. Herein, we report dual-mode luminescent crystalline microrods that spatially confine upconversion and downconversion photophysical process within defined regions using the specially designed heterogeneous structure. Through an epitaxial growth procedure, downconversion tips have been conjugated with the parent upconversion microrods in oriented directions. This spatially confined structure can effectively depress the deleterious energy depletion in lanthanide ions homogeneously doped materials, and as a result, the red, green, and blue upconversion intensities have been enhanced by 334, 225, and 22 times, respectively. Moreover, the induced tips hardly disturb the upconversion process of the microrod seeds. Upon 980 nm laser or ultraviolet lamp excitation, tunable emission colors were realized in the single tip-modified microrod, indicating potential applications of these microrods for high-level dual-mode anti-counterfeiting.

d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.

Seven-carbon-chain-containing sugars exist in several groups of important bacterial natural products. Septacidin represents a group of l-heptopyranoses containing nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. Hygromycin B, an aminoglycoside anthelmintic agent used in swine and poultry farming, represents a group of d-heptopyranoses-containing antibiotics. To date, very little is known about the biosynthesis of these compounds. Here we sequenced the genome of the septacidin producer and identified the septacidin gene cluster by heterologous expression. After determining the boundaries of the septacidin gene cluster, we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-ß-d-manno-heptose, exemplifying the involvement of ADP-sugar in microbial natural product biosynthesis. Interestingly, septacidin, a secondary metabolite from a gram-positive bacterium, shares the same ADP-heptose biosynthesis pathway with the gram-negative bacterium LPS. In addition, two acyltransferase-encoding genes sepD and sepH, were proposed to be involved in septacidin side-chain formation according to the intermediates accumulated in their mutants. In hygromycin B biosynthesis, an isomerase HygP can recognize S-7-P and convert it to ADP-d-glycero-ß-d-altro-heptose together with GmhA and HldE, two enzymes from the Escherichia coli LPS heptose biosynthetic pathway, suggesting that the d-heptopyranose moiety of hygromycin B is also derived from S-7-P. Unlike the other S-7-P isomerases, HygP catalyzes consecutive isomerizations and controls the stereochemistry of both C2 and C3 positions.

Sequential Growth of Uniform ß-NaYF4@ß-NaLnF4 (Ln = Y, Lu, Yb) Microcrystals with Luminescent Properties of Multicolor Tuning and Dual-Mode Emission.

We synthesized the uniform core-shell microstructured compounds with hexagonal phase NaYF4:Er/Yb microrods as the core and hexagonal phase NaLnF4 (NaYbF4, NaLuF4:Yb/Tm, NaYF4:Yb/Er, NaYF4:Eu) as the shell based on the hydrothermal reaction. These microscale core-shell structures provided a platform for the spatially confining optical process while possessing high luminescence efficiency. The thickness of the shell could be controlled by adjusting the amounts of shell precursor, which significantly affected the intensity of the shell dopant ions emission and the emission color of core-shell upconversion luminescence (UCL). The uniform NaYF4@NaLnF4 (Ln = Y, Lu, Yb) microrods, with a series of rare-earth ions doped into the core and shell layer at various doping concentrations, achieved color-tuning of the upconversion (UC) emission and dual-mode emission at the single-microcrystal level, thus allowing the efficient utilization of core-shell microcrystals in the photonics and security labeling. This study suggests a new class of luminescent materials in the microscopic field.