[Repair effect of different doses of human umbilical cord mesenchymal stem cells on white matter injury in neonatal rats]. / 不同剂量人脐带间å è´¨å¹²ç»†èƒžç§»æ¤å¯¹æ–°ç”Ÿå¤§é¼ è„‘ç™½è´¨æŸä¼¤çš„ä¿®å¤ä½œç”¨.

OBJECTIVES: To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. METHODS: Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. RESULTS: At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). CONCLUSIONS: Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.

tert-Butyl Nitrite-Induced Radical Nitrile Oxidation Cycloaddition: Synthesis of Isoxazole/Isoxazoline-Fused Benzo 6/7/8-membered Oxacyclic Ketones.

A practical metal-free and additive-free approach for the synthesis of 6/7/8-membered oxacyclic ketone-fused isoxazoles/isoxazolines tetracyclic or tricyclic structures is reported through Csp3-H bond radical nitrile oxidation and the intramolecular cycloaddition of alkenyl/alkynyl-substituted aryl methyl ketones. This convenient approach enables the simultaneous formation of isoxazole/isoxazoline and 6/7/8-membered oxacyclic ketones to form polycyclic architectures by using tert-butyl nitrite (TBN) as a non-metallic radical initiator and N-O fragment donor.

Palladium/Norbornene Cooperative Catalysis Bifunctionalization: Acylation/Cyanation of Aryl Iodides by Cleaving C-CN Bond of Aryl Acyl Nitrile.

A palladium/norbornene catalyzed two-component coupling process involving acylation/cyanation of aryl iodides is reported. In this work, aryl acyl nitrile compounds are cleverly selected to provide both nitrile and acyl sources by palladium-catalyzed cleavage of the C-CN bond as both an electrophilic reagent and a termination reagent. This is the first example of C-CN bond cleavage bifunctionalization of aryl iodides. After a series of important NBE derivatives are screened, the products resulting from the bifunctionalization of aryl iodides are smoothly obtained. This strategy has a wide range of substrates and good functional group compatibility. Moreover, this synthetic protocol demonstrated a good application for the synthesis of diverse O,N,C-substituted isoindolinones.

[Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2]. / æ–°ç”Ÿå„¿æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“23例临床分析.

OBJECTIVES: To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed. RESULTS: All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity. CONCLUSIONS: The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Synthesis of Diversified Pyrazolo[3,4-b]pyridine Frameworks from 5-Aminopyrazoles and Alkynyl Aldehydes via Switchable C≡C Bond Activation Approaches.

A cascade 6-endo-dig cyclization reaction was developed for the switchable synthesis of halogen and non-halogen-functionalized pyrazolo[3,4-b]pyridines from 5-aminopyrazoles and alkynyl aldehydes via C≡C bond activation with silver, iodine, or NBS. In addition to its wide substrate scope, the reaction showed good functional group tolerance as well as excellent regional selectivity. This new protocol manipulated three natural products, and the arylation, alkynylation, alkenylation, and selenization of iodine-functionalized products. These reactions demonstrated the potential applications of this new method.

Iodine-Promoted Oxidative Cyclization of Methyl Azaarenes and α-Amino Ketones for One-Pot Synthesis of 2-Azaaryl-5-aryl Oxazoles.

A high efficiency protocol was developed for the synthesis of 2,5-disubstituted oxazoles via iodine-promoted oxidative domino cyclization. These reactions were performed with readily available methyl azaarenes and α-amino ketones under metal-free conditions. This protocol is a simple method with high functional group compatibility, a wide range of substrates, and excellent yield, providing a new way to synthesize azaarene-attached oxazoles.

Iodine-catalyzed oxidative annulation: facile synthesis of pyrazolooxepinopyrazolones via methyl azaarene sp3 C-H functionalization.

An iodine-catalyzed methyl azaarene sp3 C-H functionalization has been developed for the synthesis of a seven-membered O-heterocyclic architecture containing three different heterocyclic aromatic hydrocarbons. This method can be applied to a wide range of substituted methyl azaarenes and diverse 2,4-dihydro-3H-pyrazol-3-ones, and brings about the efficient preparation of 2,9-dihydrooxepino[2,3-c:6,5-c']dipyrazol-3(7H)-ones in high yields with the merits of low catalyst loading, good functional group tolerance and metal-free conditions.

Synthesis of Diverse Pentasubstituted Pyrroles by a Gold(I)-Catalyzed Cascade Rearrangement-Cyclization of Tertiary Enamide.

An efficient Au(I)-catalyzed intramolecular cascade reaction of tertiary enamides tethered an alkynyl group has been developed. The process is composed of a propargyl-claisen rearrangement and 5-exo-dig cyclization. This protocol provided a powerful method for the preparation of a variety of pentasubstituted pyrroles derivatives with excellent functional group tolerance in excellent yields. Scale-up experiment and chemical transformations of products exhibited the versatility of tertiary enamides in organic synthesis again.

A multicenter clinical study: personalized medication for advanced gastrointestinal carcinomas with the guidance of patient-derived tumor xenograft (PDTX).

BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.

Iodine-Mediated Domino Cyclization for One-Pot Synthesis of Indolizine-Fused Chromones via Metal-Free sp3 C-H Functionalization.

An efficient method for the synthesis of new indolizine-fused chromones has been accomplished from ethyl (E)-3-(2-acetylphenoxy)acrylates and pyridines in a "one-pot" manner. Facile operation in open-air, metal-free, and mild conditions renders this protocol particularly practical and attractive. Moreover, this method can simultaneously construct two molecular fragments of chromone and indolizine. Scale-up experiment and the construction of natural products further prove the practicability of this strategy.

Nickel-Catalyzed Arylcarbamoylation of Alkenes of N-(o-Iodoaryl)acrylamides with Nitroarenes via Reductive Aminocarbonylation: Facile Synthesis of Carbamoyl-Substituted Oxindoles.

Nickel-catalyzed arylcarbamoylation reactions of alkenes of N-(o-haloaryl)acrylamides with CO and nitroarenes via reductive aminocarbonylation to produce carbamoyl-substituted oxindoles with an all-carbon quaternary stereogenic center are presented. Starting with N-(o-haloaryl)acrylamides, simple CO, and inexpensive nitroarenes and using a Ni catalyst, a dinitrogen-based ligand, a Zn reductant, a TMSCl additive, and a base system, this protocol enables the synthesis of various carbamoyl-substituted oxindoles and allows the efficient late-stage derivatization of valuable molecules.

Cascade Wolff Rearrangement/Acylation: A Metal-Free and Eco-Friendly Approach for 4-Hydroxy-pyrazolo[3,4-b]pyridin-6-ones and N-Pyrazole Amides Synthesis from 5-Aminopyrazoles and α-Diazoketones.

A highly chemoselective cascade Wolff rearrangement/acylation reaction between 5-aminopyrazoles and diazo compounds has been developed. The protocol can facilitate the switchable synthesis of 4-hydroxy-pyrazolo[3,4-b]pyridin-6-ones and N-pyrazole amides with the merits of a broad substrate scope, high functional group compatibility, and green and sustainable performance manner. All reactions proceeded efficiently without any catalyst and additives (acid and base) and resulted in the release of benign N2, wherein diethyl carbonate served as a green benign solvent.

Iodine-imine Synergistic Promoted Povarov-Type Multicomponent Reaction for the Synthesis of 2,2'-Biquinolines and Their Application to a Copper/Ligand Catalytic System.

An efficient iodine-imine synergistic promoted Povarov-type multicomponent reaction was reported for the synthesis of a practical 2,2'-biquinoline scaffold. The tandem annulation has reconciled iodination, Kornblum oxidation, and Povarov aromatization, where the methyl group of the methyl azaarenes represents uniquely reactive input in the Povarov reaction. This method has broad substrate scope and mild conditions. Furthermore, these 2,2'-biquinoline derivatives had been directly used as bidentate ligands in metal-catalyzed reactions.

One-Pot Synthesis of Chromone-Fused Pyrrolo[2,1-a]isoquinolines and Indolizino[8,7-b]indoles: Iodine-Promoted Oxidative [2 + 2 + 1] Annulation of O-Acetylphenoxyacrylates with Tetrahydroisoquinolines and Noreleagnines.

An iodine-promoted one-pot cascade oxidative annulation reaction has been developed for the synthesis of chromone-fused-pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles from o-acetylphenoxyacrylates, tetrahydroisoquinolines, and noreleagnines. This process underwent a logical approach to both chromone-fused-pyrrolo[2,1-a]isoquinolines and chromone-fused-indolizino[8,7-b]indoles isolamellarin derivatives. Manipulations of l-menthol and dl-α-tocopherol demonstrate the applications of this strategy.

Investigation Into the Current Situation and Analysis of the Factors Influencing Extrauterine Growth Retardation in Preterm Infants.

Objective: This study aims to explore the occurrence of extrauterine growth retardation (EUGR) in preterm infants with a gestational age of <34 weeks, at discharge, and the factors influencing the occurrence of EUGR. Method: A retrospective analysis of 691 preterm infants with a gestational age of less than 34 weeks, born in our hospital over the past 3 years. At discharge, the growth indicators head circumference, weight, and length were used to divide the infants into an EUGR group (n = 255) and the non-EUGR group (n = 436). The occurrence of EUGR and its influencing factors were then analyzed. Results: Of the 691 preterm infants evaluated for inclusion in the study, 255 cases (36.9%) met the requirements of EUGR at discharge. The different growth indicators used, i.e., weight, length, and head circumference, classified the infants differently. The incidence of EUGR using these measures was 30.2% (209), 27.9% (193), and 23.2% (161), respectively. The results of a univariate analysis showed that gestational age, birth weight, intrauterine growth retardation (IUGR), maternal gestational hypertension, age at which the infant commenced feeding, duration of the application of an invasive ventilator, length of hospital stay, nosocomial infection, respiratory and gastrointestinal diseases, symptomatic patent ductus arteriosus, and the early onset of neonatal sepsis were correlated with the occurrence of EUGR. Further logistic multivariate regression analysis revealed that low gestational age, low birth weight, complicated IUGR, respiratory distress syndrome, and necrotizing enterocolitis were independent risk factors for EUGR in preterm infants with a gestational age <34 weeks. Conclusion: In preterm infants with a gestational age <34 weeks in our hospital, there is a high incidence of EUGR, which is affected by factors such as the gestational age, birth weight, IUGR, respiratory distress syndrome, necrotizing enterocolitis, and other factors.

A Solid-State Fluorescence Switch Based on Triphenylethene-Functionalized Dithienylethene With Aggregation-Induced Emission.

The development of novel dithienylethene-based fluorescence switches in the aggregated state, and the solid state is highly desirable for potential application in the fields of optoelectronics and photopharmacology. In this contribution, three novel triphenylethene-functionalized dithienylethenes (1-3) have been designed and prepared by appending triphenylethene moieties at one end of dithienylethene unit. Their chemical structures are confirmed by 1H NMR, 13C NMR, and HRMS (ESI). They display good photochromic behaviors with excellent fatigue resistance upon irradiation with UV or visible light in Tetrahydrofuran (THF) solution. Before irradiation with UV light, they exhibit Aggregation Induced Emission (AIE) properties and luminescence behaviors in the solid state. Moreover, upon alternating irradiation with UV/visible light, they display effective fluorescent switching behaviors in the aggregated state and the solid state. The experimental results have been validated by the Density Functional Theory (DFT) calculations. Thus, they can be utilized as novel fluorescence switches integrated in smart, solid-state optoelectronic materials and photopharmacology.

External-oxidant-free amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines.

A new copper-catalyzed two-component amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines as the benzoyloxy sources is developed. Chemoselectivity of this method toward amino-benzoyloxylation or oxy-benzoyloxylation of alkenyl ketoximes relies on the position of the tethered olefins, and provides an external-oxidant-free alkene difunctionalization route that directly utilizes O-benzoylhydroxylamines as the benzoyloxy radical precursors and internal oxidants for the divergent synthesis of cyclic nitrones and isoxazolines.

Arylacetylenes as two-carbon synthons: synthesis of eight-membered rings via C[triple bond, length as m-dash]C bond cleavage.

The first synthesis of eight-membered N-containing heterocycles by oxidative bicyclization/ring extension of arylacetylenes and aryl amines has been achieved. This protocol uses arylacetylene as an unusual two-carbon synthon by incorporating the two parts of the cracked C[triple bond, length as m-dash]C bond into the final product, which provides a new method for using arylacetylenes as two-carbon synthons and further enriches C[triple bond, length as m-dash]C bond cleavage methodology. Moreover, this multi-component reaction can provide diverse fused elegant eight-membered N-heterocycles under mild conditions with wide substrate scopes.

Splitting Methyl Ketones into Two Parts: Synthesis of 4(3H)-Quinazolinones via Consecutive Cyclization/Ring-Opening Reaction.

The first synthesis of arylquinazolinones has been disclosed via the consecutive oxidative cyclization/ring-opening of anilines and methyl ketones. This transformation is characterized by the splitting of the methyl ketone as acyl and C1 sources through C(CO)-C(sp3) bond cleavage, using DMSO as a C1 source via C-S bond cleavage, which expands the use of methyl ketones as valuable building blocks and enriches the library of preparation quinazolinones. Moreover, preliminary mechanistic studies indicate that this multicomponent reaction underwent a consecutive cyclization/ring-opening sequence.