Comparison of Third-Generation Sequencing and Routine Polymerase Chain Reaction in Genetic Analysis of Thalassemia.

CONTEXT.­: Thalassemia is the most widely distributed monogenic autosomal recessive disorder in the world. Accurate genetic analysis of thalassemia is crucial for thalassemia prevention. OBJECTIVE.­: To compare the clinical utility of a third-generation sequencing-based approach termed comprehensive analysis of thalassemia alleles with routine polymerase chain reaction (PCR) in genetic analysis of thalassemia and explore the molecular spectrum of thalassemia in Hunan Province. DESIGN.­: Subjects in Hunan Province were recruited, and hematologic testing was performed. Five hundred four subjects positive on hemoglobin testing were then used as the cohort, and third-generation sequencing and routine PCR were used for genetic analysis. RESULTS.­: Of the 504 subjects, 462 (91.67%) had the same results, whereas 42 (8.33%) exhibited discordant results between the 2 methods. Sanger sequencing and PCR testing confirmed the results of third-generation sequencing. In total, third-generation sequencing correctly detected 247 subjects with variants, whereas PCR identified 205, which showed an increase in detection of 20.49%. Moreover, α triplications were identified in 1.98% (10 of 504) hemoglobin testing-positive subjects in Hunan Province. Seven hemoglobin variants with potential pathogenicity were detected in 9 hemoglobin testing-positive subjects. CONCLUSIONS.­: Third-generation sequencing is a more comprehensive, reliable, and efficient approach for genetic analysis of thalassemia than PCR, and allowed for a characterization of the thalassemia spectrum in Hunan Province.

A preliminary investigation of the relationship between 18F-FDG PET/CT metabolic parameters and prognosis in angioimmunoblastic T-cell lymphoma.

Purpose: The goal of the study was to determine the prognostic significance of metabolic parameters in baseline 18F-FDG PET/CT images obtained from patients with angioimmunoblastic T-cell lymphoma (AITL). Methods: Forty patients with pathologically diagnosed AITL who had baseline 18F-FDG PET/CT between May 2014 and May 2021 were assessed as part of this study. Maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), and total metabolic tumor volume (TMTV) were obtained and analyzed. In addition, many relevant features were evaluated, including sex, age, staging, International Prognostic Index (IPI), prediction index for T-cell lymphoma (PIT), Ki-67, and so on. Estimates of progression-free survival (PFS) and overall survival (OS) were determined using the log-rank test and Kaplan-Meier. Results: The median follow-up was 30.2 months (interquartile range 9.82-43.03). Throughout the follow-up period, 29 (72.5%) deaths occurred and 22 (55.0%) patients made progress. The rates for 2- and 3-year PFS were 43.6% and 26.4%, respectively. The 3- and 5-year OS were 42.6% and 21.5%. For TMTV, TLG, and SUVmax, the cut-off values were 87.0 cm3, 711.1, and 15.8, respectively. Poorer PFS and OS were substantially correlated with high SUVmax and TLG. An increased TMTV suggested a shorter OS. TLG performed independently as OS predictors in multivariate analysis. The risk score for predicting the prognosis of AITL includes the TMTV, TLG, SUVmax, and IPI scores, with 4.5 for TMTV, 2 for TLG, 1.5 for IPI scores, and 1 for SUVmax. Three risk categories of patients with AITL had 3-year OS rates of 100.0%, 43.3%, and 25.0%, respectively. Conclusion: Baseline TLG was a strong predictor of OS. Here a new prognostic scoring system for AITL based on the clinical indicators and PET/CT metabolic parameters was constructed, which might make stratification of prognosis easy and also help to individualize treatment.

Clinical impacts of genome-wide noninvasive prenatal testing for rare autosomal trisomy.

BACKGROUND: Genome-wide noninvasive prenatal testing identifies several rare autosomal trisomies in the general obstetrical population, but its use is questioned by its low positive predictive value. Furthermore, the origin of rare autosomal trisomies and the clinical effect of reporting them has not been sufficiently investigated. In addition, professional societies express their need for data assessing the clinical use of genome-wide noninvasive prenatal testing for rare autosomal trisomies for years. OBJECTIVE: This study aimed to investigate the origin of rare autosomal trisomies and the clinical effect of disclosing rare autosomal trisomies in clinical settings. STUDY DESIGN: Women who received noninvasive prenatal testing between March 2021 and March 2022 were prospectively enrolled. Clinical follow-up and cytogenetic and molecular investigations were performed. Posthoc analysis was performed to investigate the association between placental mosaicism and clinical outcomes. RESULTS: Overall, 154 rare autosomal trisomies were identified in 89,242 pregnancies (0.17%) through noninvasive prenatal testing. In the 120 cases in which cytogenetic and molecular investigations were carried out, the rare autosomal trisomies were found to originate from true fetal mosaicism (n=5), uniparental disomy (n=5), maternal mosaic trisomy (n=3), maternal malignancy (n=1), and confined placental mosaicism (n=106). Clinical follow-up showed that 40% of all rare autosomal trisomy cases had adverse perinatal outcomes. In women with false-positive noninvasive prenatal testing results originating from confined placental mosaicism, the frequency of adverse perinatal outcomes was 26%. More importantly, the placental mosaicism ratio revealed by noninvasive prenatal testing was significantly higher in women who experienced adverse perinatal outcomes than those who did not (0.688 vs 0.332; P<.001). CONCLUSION: Women with noninvasive prenatal testing results indicative of rare autosomal trisomies are at risk of adverse perinatal outcomes, and that risk can be stratified using chromosomes and the mosaicism ratio revealed by noninvasive prenatal testing. Our data are valuable for obstetrical caregivers advising a patient with a noninvasive prenatal testing result indicative of a rare autosomal trisomy and a false-positive diagnosis and for managing risks during pregnancy.

Dynamically monitoring lymphatic and vascular systems in physiological and pathological conditions of a swine model via a portable NIR-II imaging system with ICG.

Objective: NIR-II imaging with indocyanine green (ICG) has been clinically used in liver tumor resection. However, few data are available concerning the application of ICG-NIR-II in lymphatic and vascular systems in clinic. To expand the application and promote the clinical translation of this approach, we aimed to investigate the feasibility of ICG-NIR-II imaging for monitoring both lymphatic and vascular systems in physiological and pathological conditions using a swine model and compared it to ICG-NIR-I imaging. Methods: we constructed a portable NIR-II imaging system suitable for large animals. Different simulated clinical scenarios in lymphatic and vascular systems of pigs, including lymphatic drainage, lymphorrhea, lymphatic obstruction, lymphatic reconstruction in flaps, venous thrombus formation and vascular anastomosis were modeled to evaluate the reliability of our NIR-II imaging system and the imaging quality of ICG in the NIR-I/II window. Results: Under different simulated clinical scenarios, our portable NIR-II imaging system showed good reliability for pigs. With the help of the portable imaging system, dynamical visualization of lymph vessels, lymph nodes and blood vessels of pigs in different clinical scenarios could be achieved in NIR-II imaging by using the tail fluorescence of ICG. Moreover, ICG-NIR-II imaging has lower background fluorescence and higher resolution than ICG-NIR-I imaging. Conclusions: We demonstrated the first application of a portable NIR-II imaging system for dynamically monitoring both lymphatic and vascular systems in physiological and pathological conditions using a swine model. Our study indicates that ICG-NIR-II imaging be a promising approach for the diagnosis of malfunctions in lymphatic and vascular systems and the surgical navigation of microsurgery and reconstructive surgery.

Bismuth Quantum Dot (Bi QD)/Polydimethylsiloxane (PDMS) Nanocomposites with Self-Cleaning and Antibacterial Activity for Dental Applications.

In the oral microenvironment, bacteria colonies are easily aggregated on the tooth-restoration surface, in the manner of a biofilm, which usually consists of heterogeneous structures containing clusters of a variety of bacteria embedded in an extracellular matrix, leading to serious recurrent caries. In this contribution, zero-dimensional (0D) bismuth (Bi) quantum dots (QDs) synthesized by a facile solvothermal method were directly employed to fabricate a Bi QD/polydimethylsiloxane (PDMS)-modified tooth by simple curing treatment. The result demonstrates that the as-fabricated Bi QD/PDMS-modified tooth at 37 °C for 120 min not only showed significantly improved hydrophobic performance with a water contact angle of 103° and 115° on the tooth root and tooth crown, respectively, compared to that (~20° on the tooth root, and ~5° on the tooth crown) of the pristine tooth, but also exhibited excellent antibacterial activity against S. mutans, superior biocompatibility, and biosafety. In addition, due to the highly photothermal effect of Bi QDs, the antibacterial activity of the as-fabricated Bi QD/PDMS-modified tooth could be further enhanced under illumination, even at a very low power density (12 mW cm-2). Due to the facile fabrication, excellent hydrophobicity, superior antibacterial activity, and biocompatibility and biosafety of the Bi QD/PDMS-modified tooth, it is envisioned that the Bi QD/PDMS-modified tooth with a fascinating self-cleaning and antibacterial performance can pave the way to new designs of versatile multifunctional nanocomposites to prevent secondary caries in the application of dental restoration.

Prenatal genetic diagnosis of tetrasomy 18p from maternal trisomy 18p: a case report.

BACKGROUND: Tetrasomy 18p syndrome is a rare chromosomal disorder that is caused by the presence of isochromosome 18p. Most tetrasomy 18p cases are de novo cases and maternal origin of trisomy 18p is a rare condition. At present, only four cases of maternal origin have been reported in worldwide.This is the fifth case of tetrasomy 18p originating from maternal trisomy 18p. The mother of the fetus studied had no apparent disease phenotype. CASE PRESENTATION: The current case report is to describe a fetus with confirmed 18p tetrasomy as detected by karyotyping and Single Nucleotide Polymorphism array (SNP array) analysis. However, the fetus showed normal phenotypic features that were observed using ultrasound scans. The mother and maternal grandfather were phenotypically normal and healthy; however, they were diagnosed with trisomy 18p, which was confirmed by conventional karyotyping and SNP array. CONCLUSIONS: We report a case of 18p tetrasomy in a fetus whose mother and grandfather had 18p trisomy. The mother and grandfather were phenotypically normal. Our case report findings provide an important reference for the genetic counseling of trisomy 18p in the future.

DABCO as a practical catalyst for aromatic halogenation with N-halosuccinimides.

A simple and practical synthetic approach for synthesis of aromatic halides is developed. Simple Lewis base, DABCO, is used as the catalyst. This arene halogenation process proceedes conveniently and efficiently at ambient conditions, providing the desired products in good to excellent yields and selectivity.

Tin Oxide (SnO2) Nanoparticles: Facile Fabrication, Characterization, and Application in UV Photodetectors.

Tin oxide (SnO2) nanomaterials are of great interest in many fields such as catalytic, electrochemical, and biomedical applications, due to their low cost, suitable stability characteristics, high photosensitivity, etc. In this contribution, SnO2 NPs were facilely fabricated by calcination of tin (II) oxalate in air, followed by a liquid-phase exfoliation (LPE) method. Size-selected SnO2 NPs were easily obtained using a liquid cascade centrifugation (LCC) technique. The as-obtained SnO2 NPs displayed strong absorption in the UV region (~300 nm) and exhibited narrower absorption characteristics with a decrease in NP size. The as-fabricated SnO2 NPs were, for the first time, directly deposited onto a poly(ethylene terephthalate) (PET) film with a regular Ag lattice to fabricate a flexible working electrode for a photoelectrochemical (PEC)-type photodetector. The results demonstrated that the SnO2-NP-based electrode showed the strongest photoresponse signal in an alkaline electrolyte compared with those in neutral and acidic electrolytes. The maximum photocurrent density reached 14.0 µA cm-2, significantly outperforming black phosphorus nanosheets and black phosphorus analogue nanomaterials such as tin (II) sulfide nanosheets and tellurene. The as-fabricated SnO2 NPs with relatively larger size had better self-powered photoresponse performance. In addition, the as-fabricated SnO2-NP-based PEC photodetector exhibited strong cycling stability for on/off switching behavior under ambient conditions. It is anticipated that SnO2 nanostructures, as building blocks, can offer diverse availabilities for high-performance self-powered optoelectronic devices to realize a carbon-neutral or carbon-free environment.

2D MXene Ti3C2T x nanosheets in the development of a mechanically enhanced and efficient antibacterial dental resin composite.

The bacterial accumulation at the margins of dental resin composites is a main cause of secondary caries, which may further lead to prosthodontic failure. In this regard, this study for the first time incorporated 2D MXene Ti3C2Tx nanosheets (NSs) into epoxy resin at different mass ratios (0, 0.5, 1.0, and 2.0 wt%) by solution blending and direct curing for dental applications. Compared to the pure resin, the as-fabricated MXene/resin composite not only exhibited improved mechanical and abrasive results but also displayed gradually improved antibacterial activity with MXene loading which was further enhanced by illumination in natural light due to the high photothermal efficiency of MXene. In addition, the cytotoxicity result demonstrated that the MXene-modified resin did not cause severe damage to normal cells. This novel MXene/resin nanocomposite could pave the way for new designs for high-performance, multifunctional nanocomposites to effectively protect dental health in daily life.

In-situ regulation of acid sites on Mn-based perovskite@mullite composite for promoting catalytic oxidation of chlorobenzene.

A series of Sm-Mn perovskite@mullite composites with different amounts of acid sites were successfully synthesized by regulating the level of in situ etched-surface modification. X-ray diffraction (XRD) test showed that the crystal structure of catalyst gradually changed from perovskite to perovskite@mullite composites and mullite. The characterization of temperature programmed desorption with ammonia (NH3-TPD) confirmed the acid sites on the surface of catalyst can be deployed by the in-situ modification. The temperature-programmed reduction with hydrogen (H2-TPR), and N2 adsorption-desorption showed that the surface modification also increased the reducibility, surface area, and mesoporosity of catalyst. The catalytic activities were compared by a long-term catalytic oxidation of chlorobenzene evaluation for 20 h of uninterrupted reaction at a relatively low temperature of 300 °C, and the Sm-Mn perovskite@mullite composite (SMPM-1.2) possessed the best catalytic stability. The X-ray photoelectron spectroscopy (XPS) measurement determined that the high ratios of lattice oxygen and tetravalent manganese did not improve the stability of catalyst in the catalytic oxidation of chlorobenzene, but the activities trends of samples were consistent with the change of surface (Mn4++Mn3+)/Mn2+ ratios. Meanwhile, the catalytic experiments for benzene, toluene, o-xylene and acetone showed that the as-prepared catalyst was also suitable for the efficient removal of the different types of VOCs. This work supplied a method for the further development of high activity catalysts for the removal of VOCs.

CdS@CdSe Core/Shell Quantum Dots for Highly Improved Self-Powered Photodetection Performance.

Uniform, well-defined cadmium sulfide@cadmium selenide core/shell quantum dots (CdS@CdSe QDs) were, for the first time, successfully synthesized by a solvothermal method and chemical bath growth for photoelectrochemical activities. The as-synthesized CdS@CdSe QDs not only exhibit superior self-powered photoresponse behavior and excellent stability under ambient conditions but also display significantly improved current densities and photoresponsivity compared to those of individual CdS QDs or CdSe QDs, mainly due to the built-in electric field, and thus have great potential in the fields of renewable energy and renewable energy consumption for carbon neutrality target achievement.

Hollow MoS2/Co nanopillars with boosted Li-ion diffusion rate and long-term cycling stability.

Hollow MoS2/Co-0.1 nanopillars were successfully synthesized by sulfurizing CoMoO4 and subsequent acid etching, which were used as the anode material for lithium ion batteries. The introduction of suitable metal Co into MoS2 nanopillars effectively accelerates electron/ion transport kinetics, leading to high specific capacity and superior rate capability and cycling stability.

Correction: RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting.

Correction for 'RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting' by Yu Pei et al., Chem. Commun., 2021, 57, 1498-1501, DOI: 10.1039/D0CC07565E.

Stable Rooted Solid Electrolyte Interphase for Lithium-Ion Batteries.

Metal oxide-based materials are attractive anode candidates for lithium-ion batteries (LIBs) because of their high theoretical capacity. However, these materials suffer from large volume expansion and poor stability of solid electrolyte interphase (SEI) during the charge-discharge process, casusing rapid capacity degradation. Herein, we report that Li3PO4-rooted and intact SEI in situ formed on the phosphate-modified SnO2/CNFs during cycling. The phosphate anions in the anode, could serve as the root to form Li3PO4 by bonding with Li ions and participate in the formation of the SEI, thus firmly anchoring and stabilizing the SEI layer. The rooted Li3PO4 and enriched LiF in the SEI could synergistically enhance the Li-ion diffusion, significantly reduce the volume expansion, and lead to ultrastable cycling performance over 1100 charge-discharge cycles at 1 A g-1. This work provides a new avenue for forming stable SEI rooted into the anode and inspires the development of interface engineering toward electrochemical energy storage.

A More Universal Approach to Comprehensive Analysis of Thalassemia Alleles (CATSA).

The aim of the study was to assess the clinical utility of a third-generation sequencing (TGS) approach termed comprehensive analysis of thalassemia alleles (CATSA) for identifying both α and ß thalassemia genetic carrier status. Prospective blood samples (n = 1759) with abnormal hemoglobin parameters were screened for pathogenic thalassemia variants by CATSA on the PacBio TGS platform. In 1159 individuals, a total of 1317 pathogenic thalassemia variants were identified and confirmed by independent PCR-based tests. Of the total thalassemia variants detected, the α-variant --SEA (35.4%) and ß-variant c.126_129delCTTT (15%) were the most common. CATSA was also able to detect three types of rare HBA structural variants as well as five rare HBA2, three HBA1, and 10 HBB single-nucleotide variations/insertions and deletions. Compared with standard thalassemia variant PCR panel testing, CATSA identified all panel variants present, with no false-negative results. Carrier assignment was improved through identification of rare variants missed by the panel test. On the basis of allelic coverage, reliability, and accuracy, TGS with long-range PCR presents a comprehensive approach with the potential to provide a universal solution for thalassemia genetic carrier screening. It is proposed that CATSA has immediate clinical utility as an effective carrier screening approach for at-risk couples.

Crystallinity Effect of NiFe LDH on the Growth of Pt Nanoparticles and Hydrogen Evolution Performance.

NiFe layered double hydroxides (LDHs) usually exhibit high water-dissociation ability in the alkaline media and also provide an ideal substrate for anchoring noble metals, such as platinum (Pt), due to the 2D microstructure. Appropriate regulation of the interaction between Pt and substrate could enhance the intrinsic activity of composite catalysts toward the hydrogen evolution reaction (HER) in the alkaline media. Herein, we electrodeposit Pt nanoparticles on amorphous NiFe LDH (Pt/NiFe-ED) or crystalline NiFe LDH (Pt/NiFe-HD) to regulate the interaction between Pt and NiFe LDH. Experimental results reveal that Pt nanoparticles on NiFe-ED are smaller than those on NiFe-HD and possess a narrower size distribution. Thus, Pt/NiFe-ED (300 µM) exhibits a much lower overpotential of 81 mV at 100 mA cm-2 than Pt/NiFe-HD. In contrast, Pt/NiFe-HD exhibits a higher intrinsic activity than Pt/NiFe-ED, which could be caused by the easily elongated Pt-O bond. These findings provide new opportunities to understand the relationship between activity and crystallinity of substrates in the composite electrocatalyst.

[Value of chromosomal microarray analysis for the prenatal diagnosis of pregnancy with high risk signaled by non-invasive prenatal testing].

OBJECTIVE: To explore the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with high risk signaled by non-invasive prenatal testing (NIPT). METHODS: From June 2017 to August 2019, 628 pregnant women with high risk signaled by NIPT underwent invasive prenatal diagnosis. Amniotic fluid or cord blood samples were subjected to chromosomal karyotyping analysis or CMA. Pregnancy outcome and postnatal conditions of the fetuses were followed up. RESULTS: The positive predictive value for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidy, other rare trisomies and copy number variants (CNVs) among the 628 women were 86.4% (127/147), 41.7% (30/72), 12.9% (4/31), 43.7% (101/231), 16.5% (14/85) and 52.2% (35/67), respectively. In 218 samples with normal karyotype, 5.5% (12/218) of additional pathogenic CNVs and 2.3% (5/218) of loss of heterozygosity were detected by CMA. CONCLUSION: CMA combined with karyotyping analysis can be used as first-tier test for prenatal diagnosis for women with high-risk signaled by NIPT.

Domino Heck/Hiyama cross-coupling: trapping of the σ-alkylpalladium intermediate with arylsilanes.

A palladium-catalyzed domino Heck cyclization/Hiyama coupling reaction by the trapping of the σ-alkylpalladium intermediate with arylsilanes is described. A wide range of aryl-tethered alkenes and arylsilanes are all compatible with the reaction conditions. This approach shows good yields and excellent functional group tolerance, presenting a more practical and sustainable alternative to the conventional domino Heck cyclization/Suzuki coupling reaction.

Design of pyridinylphosphinate-based blue iridium phosphors for high-efficiency organic light-emitting diodes.

At present, cyclometalated iridium (Ir)(iii) complexes are the most promising emitters for OLEDs. Contrary to well-developed Ir(iii)-based red and green phosphorescent complexes, the efficient blue emitters are limited and the performances of blue OLEDs are still not satisfactory. Inspired by this, we designed two novel blue Ir(iii) complexes employing 2-(2,4-difluoropyridyl)pyridine (dfpypy) and 2,6-difluoro-3-(pyridin-2-yl)benzonitrile (FCN) as the main ligands, respectively, and phenyl(pyridin-2-yl)phosphinate (ppp) as the ancillary ligand. The rational design of the molecular structure makes the two complexes achieve blue emission and possess good electron mobility simultaneously. The devices based on the Ir(iii) phosphors exhibited good electroluminescence performances with low turn-on voltages, a peak current efficiency of 24.51 cd A-1, a maximum external quantum efficiency of 12.4%, a peak power efficiency of 21.99 lm W-1 and low efficiency roll-off. These results provide an effective strategy for the future molecular design of blue Ir(iii) complexes with good electron transport property for OLEDs.

RuCo alloy trifunctional electrocatalysts with ratio-dependent activity for Zn-air batteries and self-powered water splitting.

Herein, we reported a RuCo alloy with nitrogen-doped porous carbon (RuCo/NPC) as efficient trifunctional electrocatalysts for Zn-air batteries and water splitting. The versatility and catalytic activity of this catalyst is achieved by adjusting the Ru/Co ratio. The as-assembled Zn-air battery and overall water splitting with RuCo/NPC present outstanding catalytic performances.