A case of pediatric serum sickness like reaction (SSLR) after a 2-month re-exposure to amoxicillin.

BACKGROUND: Serum-sickness like reactions (SSLRs) to amoxicillin have been documented in the medical literature. Beta-lactams are important and commonly used medications especially in the pediatric population. Often, SSLRs present within days of and during first exposure/ingestion to the offending agent. We described a unique case of a 4-year-old boy who presented with symptoms of amoxicillin SSLR following his second course of amoxicillin with only 2 months and 10 days between his second and first course. CASE PRESENTATION: A 4-year-old boy presented to hospital with a pruritic rash on day 7 of a 10-day course of amoxicillin for otitis media accompanied by fever (38.7 degrees Celsius). On day 7 of his second course of amoxicillin, which was separated from his first course by only 2 months and 10 days, his mother noticed erythematous, raised, pruritic lesions with central clearing on his sternum. He presented to the ED with emesis, progression of the rash to his torso, back, legs, and face, hypotension, angioedema, and joint pain. His bloodwork demonstrated a leukocytosis of 18.6 × 109 g/L with neutrophilic predominance and thrombocytosis with a platelet count of 653 × 109 g/L. He was treated with 5 mg oral cetirizine daily and 1 mg/kg oral prednisone which improved his rash and angioedema. He was managed with up to 4 times the usual dose of cetirizine. He was assessed in our outpatient clinic as an outpatient and penicillin skin testing was unremarkable. A diagnosis of a probable SSLR to amoxicillin was made. CONCLUSION: We report an unusual presentation of SSLR following re-exposure to amoxicillin. Our case highlights that patients with previous asymptomatic exposure to amoxicillin can develop SSLR with repeat exposure. Although it is not uncommon for children to develop amoxicillin SSLRs after previous exposure to the drug, this case is unique because of its short time course of 2 months and 10 days months between drug courses. Penicillins are commonly used in the pediatric population. Therefore, it is important to correctly characterize adverse drug reactions to broaden our understanding of SSLRs, prevent unnecessary avoidance of the triggering agent, and improve patient management.

Combined Z-scores to assess the impact of rare autosomal trisomies that results in non-invasive prenatal screening on pregnancy outcomes.

OBJECTIVE: This study aimed to combine Z-scores to evaluate the effects of rare autosomal trisomies (RATs) in non-invasive prenatal screening (NIPS) on pregnancy outcomes at a single center. METHODS: We retrospectively collected the clinical data of women with high-risk RATs results using NIPS at a single center between January 2017 and December 2021. NIPS-positive results were separated into three groups based on the Z-value of RATs (Group1: 6 ≤ Z < 10; Group2: 10 ≤ Z < 15; Group 3: Z ≥ 15). Pregnancy outcomes of women with RATs were compared with the low-risk NIPS group. RESULTS: Overall, 83 RATs were identified in 23,321 NIPS results at our center. Prenatal diagnosis was conducted for 55 patients, and no case was confirmed, with a positive predictive value (PPV) of zero. Fifteen of these patients had adverse pregnancy outcomes, including delivered preterm and/or birth weight (9/15, 60.0 %), structural abnormalities (4/15, 26.7 %), miscarriage (1/15, 6.7 %), and intrauterine death (1/15, 6.7 %). There were 8 (8/22, 36.4 %) adverse pregnancy outcomes in Group 3, which was significantly higher than that in the low-risk NIPS group (p < 0.01). No significant difference was observed between the control group and Group 1 and Group 2 (p > 0.01). CONCLUSIONS: Clinicians should pay more attention to the RATs results when the Z-score is ≥ 15. The data are available for clinicians to guide the prenatal diagnosis of RATs and pregnancy management.

Relationships among maternal monosomy X mosaicism, maternal trisomy, and discordant sex chromosome aneuploidies.

OBJECTIVE: To explore the impact of maternal factors on the false-positive fetal sex chromosome aneuploidies (SCAs) results obtained through noninvasive prenatal screening (NIPS). METHODS: We retrospectively analyzed pregnant women with high-risk SCAs as revealed using NIPS between January 2017 and December 2022. Clinical data such as results of invasive prenatal diagnoses, copy number variation sequencing (CNV-seq) and pregnancy outcomes were analysed. RESULTS: Overall, 177 (0.6 %) women with SCA-positive results were collected from 27,941 patients who had undergone NIPS. Among them, 110 (62.2 %) pregnant women chose prenatal diagnosis and 39 (35.5 %) cases were confirmed. For the women with monosomy X false-positive results from the NIPS, 53.1 % (17/32) were found to be maternal mosaicism monosomy X. In cases with 47, XXX false-positive results, 60 % (6/10) of them were maternal 47,XXX (5 cases) or maternal mosaicism 47,XXX (1 case). One (1/6, 16.7 %) case of maternal mosaicism monosomy X was detected in the false positive results of 47, XXY/47, XYY revealed. The incidence rate of maternal sex chromosome abnormalities was positively correlated with the Z-score of ChrX. When the Z-score of ChrX ≥ 15, more than 50 % of pregnant women were found to be maternal sex chromosome abnormalities, and when Z-score ≥ 30, the incidence rate was as high as 100 %. CONCLUSIONS: Maternal monosomy X mosaicism and trisomy X respectively played an important role in the discordance of 45, X and 47, XXX revealed by NIPS. CNV-seq was recommended for the pregnant women at risk of maternal sex chromosome abnormalities, which could help clinicians to provide more accurate and efficient advice during genetic counseling and to guide appropriate prenatal diagnosis strategy for the next pregnancy.

Noninvasive prenatal screening with conventional sequencing depth to screen fetal copy number variants: A retrospective study of 19 144 pregnant women.

AIM: To investigate the detectability of noninvasive prenatal screening (NIPS) with conventional sequencing depth to detect fetal copy number variants. METHODS: We performed a retrospective study in a total of 19 144 pregnant women. Their cell-free plasma DNA were assessed for trisomy 21, trisomy 18, trisomy 13, sex chromosome aneuploidies, and genome-wide copy number variants by NIPS at conventional sequencing depth. RESULTS: Three hundred seventy-four cases (2.0%, 374/19 144) with abnormal results were detected, which including 84 cases (0.4%, 84/19 144) with high risk of trisomy 21, 18, and 13, 90 cases (0.5%, 90/19 144) with high risk of sex chromosome abnormalities (SCA), and 44 cases (0.2%, 44/19 144) with high risk of other chromosome aneuploidies. One hundred fifty-six cases (0.8%, 156/19 144) with high risk of copy number variations (CNVs) were also detected. In following prenatal diagnosis, composite positive predictive value (PPV) of trisomy 21, 18, and 13 was 69.6% (48/69). The PPV of SCAs was 37.3% (19/51). And the PPVs for CNVs was detected as 51.0% (<5 Mb), 71.4% (5 Mb ≤ CNV ≤10 Mb), 56.5% (>10 Mb). Finally, a follow-up about the pregnancy outcomes were conducted for all available cases. CONCLUSIONS: NIPS yielded high PPVs for trisomy 21, 18, and 13 aneuploidies and moderate PPVs for SCAs and CNVs. The screening effectiveness was closely related to the size of CNV fragments. Larger CNVs, especially larger than 5 Mb, could be detected more accurately by NIPS in our analytic technique. Meanwhile, diagnostic confirmation by microarray analysis was highly recommended.

Locking the Conformation of a Paddlewheel Rhodium Complex: Design, Synthesis, and Applications in Catalytic Nitrene Transfers.

The exponential proliferation of conformers makes it impossible to examine the entire population in most systems. Controlling conformational ensembles is thus pivotal in many areas of chemistry. Rh2 (esp)2 , a dicarboxylate-derived paddlewheel rhodium complex, is one of the most effective catalysts for nitrene chemistry. Its enormous success has led to preparing many analogous complexes. However, there has been little consideration for the conformational dynamics of the parent catalyst. Herein, we report a new ligand modification principle that prevents conformer interconversion. The resulting complex comprises two isolable conformers, whose structures have been determined by X-ray diffraction. Combined experimental and computational data has revealed similarities and dissimilarities between the conformationally confined and parent complexes. Three model cases have demonstrated the utility of conformational fixation in the development of stereoselective catalysts for nitrene transfer reactions. The design principle described in this study can be combined with other established modification strategies, serving as a springboard for further advancement of the chemistry of paddlewheel metal complexes.

AAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa.

Base editing technology is an ideal solution for treating pathogenic single-nucleotide variations (SNVs). No gene editing therapy has yet been approved for eye diseases, such as retinitis pigmentosa (RP). Here, we show, in the rd10 mouse model, which carries an SNV identified as an RP-causing mutation in human patients, that subretinal delivery of an optimized dual adeno-associated virus system containing the adenine base editor corrects the pathogenic SNV in the neuroretina with up to 49% efficiency. Light microscopy showed that a thick and robust outer nuclear layer (photoreceptors) was preserved in the treated area compared with the thin, degenerated outer nuclear layer without treatment. Substantial electroretinogram signals were detected in treated rd10 eyes, whereas control treated eyes showed minimal signals. The water maze experiment showed that the treatment substantially improved vision-guided behavior. Together, we construct and validate a translational therapeutic solution for the treatment of RP in humans. Our findings might accelerate the development of base-editing based gene therapies.

Prenatal diagnosis of a case with complete and uniform tetrasomy 12p by the utility of noninvasive prenatal testing.

PURPOSE: To report a rare type of Pallister-Killian syndrome (PKS) diagnosed prenatally by the utility of non-invasive prenatal testing (NIPT). METHODS: NIPT was performed in the first trimester. Conventional karyotyping and chromosomal microarray analysis (CMA) were performed on the amniotic samples in the second trimester. Copy number variation sequencing (CNV-seq) was used for the validation of fetal skin and the placental tissue after pregnancy termination. RESULTS: NIPT results showed increased signal from chromosome 12p. Subsequent prenatal diagnostic testing by karyotype revealed 47, XY, +i (12p), and CMA displayed four copies of 12p: 12p13.33-12p11.1(173786_34835641) × 4. The CNV-seq results of the fetal skin and the fetal side of placenta showed four copies of 12p13.33-p11 and an estimated chimeric duplication of 34.08 Mb (chimerism ratio: 10%) in 12 p13.33-p11, respectively. However, no abnormality was detected by CNV-seq at the maternal side of placenta. CONCLUSIONS: Our findings suggest that a positive signal from chromosome 12p on NIPT should raise suspicion for PKS. With the wide application of NIPT, the true positive of incidental finding is expected to increase.

First Report of Leaf Spot Caused by Clonostachys rosea on Tea (Camellia sinensis) in China.

Tea (Camellia sinensis), which originated in southwest of China 60 - 70 million years ago, is widely consumed as a beverage for its potential enhancing effect on human health with rich polyphenol content (Pan et al. 2022). From October to December in 2021, a disease with symptoms similar to leaf spot affected the quality and yield of tea Puer (102°73 'E, 25°07' N), Yunnan province, China. Based on the survey, leaf spot symptoms were observed on approximately 60% of tea plants in a 5,700 m2 field. The symptoms initially appeared as shrinking, yellowing, and later became circular or irregular brown spots. To isolate the pathogen, 10 symptomatic leaves were collected from 10 trees, and portions of the diseased tissue (0.5×0.5 cm) were cut at the junction of infected and healthy tissues. After surface sterilization (0.5 min with 75% ethanol and 2 min with 3% NaOCl, washed three times with sterilized distilled water), the disinfected pieces were dried and plated onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 5 days. Four single-spore isolates, FH-1, FH-5, FH-6 and FH-7, were obtained, these isolates were identical in morphology and in the sequences of internal transcribed spacer region [ITS] and translation elongation factor 1-alpha [TEF] genes. Therefore, the representative isolate FH-5 was used for further study. Fungal colonies were white or light yellow on PDA after 7 days incubated at 28ºC. Conidia were hyaline, round or oval, aseptate, occur singly or in clusters on hyphae or conidia stalks, and measured as 2.94 ± 1.79 × 1.82 ± 0.2 µm (n = 50). Primary conidiophores is Verticillium-like (Fig1.K,L), which generally formed first, 1-3-level verticillate, mostly with divergent branches and phialides, and measured as 16.67 ± 4.39 µm (n = 50). Secondary conidiophores is penicillate (Fig1.I,J), which generally appearing after one week, sometimes even more often branched, and with a length of 16.02 ± 3.83 µm (n = 50). The morphological features were consistent with the descriptions of Clonostachys rosea Schroers H.J. (Schroers et al. 1999). The pathogen was confirmed to be C. rosea by amplification and sequencing of the internal transcribed spacer region (ITS) and translation elongation factor 1-alpha (TEF) genes using primers ITS1/ITS4 and EF1-728F/EF1-986R, respectively (Fu Rongtao 2019). The sequences of PCR products were deposited in GenBank with accession numbers ON332533 (ITS) and OP080234 (TEF). BLAST searches of the obtained sequences revealed 99.22% (510/514 nucleotides) and 98.37% (241/245 nucleotides) homology with those of C. rosea HQ-9-1 form GenBank (MZ433177 and MZ451399, respectively). Phylogenetic analysis (MEGA 7.0) using the maximum likelihood method placed the isolate FH-5 in a well-supported cluster with C. rosea. The pathogenicity of FH-5 was tested through a pot assay. Ten healthy tea plants were scratched with a sterilized needle on the leaves. Plants were inoculated by spraying a spore suspension (105 spores·mL-1) of FH-5 onto leaves until runoff, and the control leaves sprayed with sterile water. Inoculated plants were put in an artificial climate box at 25℃, 70% relative humidity. The pathogenicity test was replicated three times. Symptoms developed on all inoculated leaves but not on the control leaves. Lesions around the wound edge became pale yellow, and brown spots were first observed at 72 h after inoculation, and typical lesions similar to those observed on field plants appeared after two weeks. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses (ITS and TEF) from the infected leaves but not from the noninoculated leaves. In addition, C. rosea has also been reported to cause diseases to broad bean (N. Afshari et al. 2017 ), garlic (Diaz et al. 2022), beet (Haque M.E et al. 2020) and other plants. To our knowledge, this is the first report of leaf spot on tea caused by C. rosea in China. This study provides valuable information for the identification and control of the leaf spot on tea.

[Genetic analysis of a fetus with mosaic trisomy 12 and severe heart defects and a literature review].

OBJECTIVE: To explore the genetic basis for a fetus with severe heart defect and mosaic trisomy 12, and the correlation between chromosomal abnormalities and clinical manifestations and pregnancy outcome. METHODS: A 33-year-old pregnant woman who presented at Lianyungang Maternal and Child Health Care Hospital on May 17, 2021 due to abnormal fetal heart development revealed by ultrasonography was selected as the study subject. Clinical data of the fetus were collected. Amniotic fluid sample of the pregnant women was collected and subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). The CNKI, WanFang and PubMed databases were searched with key words, with the retrieval period set as from June 1, 1992 to June 1, 2022. RESULTS: For the 33-year-old pregnant woman, ultrasonography at 22+6 gestational weeks had revealed abnormal fetal heart development and ectopic pulmonary vein drainage. G-banded karyotyping showed that the fetus has a karyotype of mos 47,XX,+12[1]/46,XX[73], with the mosaicism rate being 1.35%. CMA results suggested that about 18% of fetal chromosome 12 was trisomic. A newborn was delivered at 39 weeks of gestation. Follow-up confirmed severe congenital heart disease, small head circumference, low-set ears and auricular deformity. The infant had died 3 months later. The database search has retrieved 9 reports. Literature review suggested that the liveborn infants with mosaic trisomy 12 had diverse clinical manifestations depending on the affected organs, which had included congenital heart disease and/or other organs and facial dysmorphisms, resulting in adverse pregnancy outcomes. CONCLUSION: Trisomy 12 mosaicism is an important factor for severe heart defects. The results of ultrasound examination have important value for evaluating the prognosis of the affected fetuses.

Incidence and genetic variants of inborn errors of metabolism identified through newborn screening: A 7-year study in eastern coastal areas of China.

BACKGROUND: The incidence of inborn errors of metabolism (IEM) varies across countries and areas. Currently, there are no studies on IEM using newborn screening (NBS) in eastern coastal areas of China. We aimed to estimate the incidence and genetic variants of IEM and understand the spectrum of diseases caused by IEM and variants among them in this area. METHODS: The NBS performed by tandem mass spectrometry (MS/MS) from 2016 to 2021 was retrospectively reviewed. Heel blood was collected from all newborns 72 h after birth. Targeted massively parallel sequencing was performed for genetic analysis. RESULTS: Among 245,194 newborns, 95 were diagnosed with IEM, the overall incidence observed was-IEM: 1/2581; amino acid metabolism disorder: 1/4715; organic acid metabolism disorder: 1/11676; and fatty acid metabolism disorder: 1/11145. The incidence of different IEM was in the range of 1/245194 to 1/6452. Phenylketonuria (PKU, 1/7211) was the most common IEM, followed by methylmalonic acidemia (MMA, 1/27244), short-chain acyl-CoA dehydrogenase deficiency (SCADD, 1/30649), and citrin deficiency (CD, 1/35028). For genetic variants, the common hotspot variants found were-PAH gene for PKU: c.728G > A, c.442-1G > A, c.611A > G, c.721C > T; PTS gene for non-classical PKU: c.259C > T; MMACHC gene for MMA: c.658_660delAAG, c.609G > A; MMUT gene for MMA: c.1663G > A; ACADS gene for SCADD: c.1031A > G and c.1130C > T; and SLC25A13 gene for CD: c.1638_1660dup, c.852_855del. CONCLUSION: This study displayed the diseases and varied spectrum of IEM in eastern coastal areas of China. Implementing NBS for IEM by MS/MS combined with massively parallel sequencing can offer an improved plan for NBS to detect IEM.

A Missing Link in Multisubstituted Pyrrolidines: Remote Stereocontrol Forged by Rhodium-Alkyl Nitrene.

Pyrrolidines are significant N-heterocycles in medicinal chemistry and are among the top ten ring systems found in drug molecules. While simple derivatives are commercially available, densely decorated derivatives with precise stereochemical arrangements remain difficult to obtain. Methods for synthesizing multisubstituted pyrrolidines with nonadjacent stereocenters are particularly scarce. To bridge this gap, we report the stereoselective synthesis of remotely decorated, trisubstituted ß-prolines via Rh-catalyzed C-H amination. The transformation proceeds well in the presence of various functionalities with exclusive anti-selectivity. Carboxylic acids in the products serve as gateways for diverse downstream transformations. Furthermore, the combined experimental and computational study sheds lights on the origin of high diastereoselectivity.

Maternal Xp22.31 copy-number variations detected in non-invasive prenatal screening effectively guide the prenatal diagnosis of X-linked ichthyosis.

Background and aims: X-linked ichthyosis (XLI) is a common recessive genetic disease caused by the deletion of steroid sulfatase (STS) in Xp22.31. Maternal copy-number deletions in Xp22.31 (covering STS) can be considered an incidental benefit of genome-wide cell-free DNA profiling. Here, we explored the accuracy and clinical value of maternal deletions in Xp22.31 during non-invasive prenatal screening (NIPS). Materials and methods: We evaluated 13,156 pregnant women who completed NIPS. The maternal deletions in Xp22.31 revealed by NIPS were confirmed with maternal white blood cells by chromosome microarray analysis (CMA) or copy-number variation sequencing (CNV-seq). Suspected positive women pregnant with male fetuses were informed and provided with prenatal genetic counseling. Results: Nineteen maternal deletions in Xp22.31 covering STS were detected by NIPS, which were all confirmed, ranging in size from 0.61 to 1.77 Mb. Among them, eleven women with deletions in male fetuses accepted prenatal diagnoses, and finally nine cases of XLI were diagnosed. The nine XLI males had differing degrees of skin abnormalities, and of them, some male members of ten families had symptoms associated with XLI. Conclusion: NIPS has the potential to detect clinically significant maternal X chromosomal CNVs causing XLI, which can guide the prenatal diagnosis of X-linked ichthyosis and reflect the family history, so as to enhance pregnancy management as well as children and family members' health management.

Transcriptome analysis provides insights into the molecular mechanism of GhSAMDC1 involving in rapid vegetative growth and early flowering in tobacco.

In previous study, ectopic expression of GhSAMDC1 improved vegetative growth and early flowering in tobacco, which had been explained through changes of polyamine content, polyamines and flowering relate genes expression. To further disclose the transcript changes of ectopic expression of GhSAMDC1 in tobacco, the leaves from wild type and two transgenic lines at seedling (30 days old), bolting (60 days old) and flowering (90 days old) stages were performed for transcriptome analysis. Compared to wild type, a total of 938 differentially expressed genes (DEGs) were found to be up- or down-regulated in the two transgenic plants. GO and KEGG analysis revealed that tobacco of wild-type and transgenic lines were controlled by a complex gene network, which regulated multiple metabolic pathways. Phytohormone detection indicate GhSAMDC1 affect endogenous phytohormone content, ABA and JA content are remarkably increased in transgenic plants. Furthermore, transcript factor analysis indicated 18 transcript factor families, including stress response, development and flowering related transcript factor families, especially AP2-EREBP, WRKY, HSF and Tify are the most over-represented in those transcript factor families. In conclusion, transcriptome analysis provides insights into the molecular mechanism of GhSAMDC1 involving rapid vegetative growth and early flowering in tobacco.

Disparate phenotypes in two unfavorable pregnancies due to maternal mosaicism of a novel RET gene mutation.

Mutations in RET have been found in multiple diseases including isolated and associated congenital anomalies. Here, we report a case presented with disparate phenotypes in each pregnancy but caused by the same novel mutation. Whole-exome sequencing (WES) was performed on the proband/abortion product-parental trio and a novel missense variant in RET (chr10:43615610C > G; c.2689C > G; p.Arg897Gly) was identified. The mother was a low-level somatic carrier of this new mutation, with 17.3% in blood, 19.1% in oralmucous membrane, and 15.7% in urine by droplet digital polymerase chain reaction (dd PCR). Our finding not only broadens the mutation spectrum of RET but also gives supportive genetic counseling and timely guidance on fertility choices.

An integrated optical waveguide micro-cantilever system for chip-based AFM.

An optical waveguide cantilever system with a tip is introduced as the displacement detection system of chip-based atomic force microscopy (AFM) system. A chip-based AFM on optical waveguide is demonstrated with sensitivity of up to 4.0 × 10-2 nm-1 , which is mainly constructed by a 210 nm thick optical waveguide cantilever with a nano-tip. The nano-tip is a height of 1.2 µm and diameter of 140 nm. This integrated on-chip system provides a displacement range of approximately ±0.4 µm, which makes it possible for the device to be used for AFM imaging and pays the way for further performance improvement.

Prenatal Diagnostic Testing Following High-Risk Result from Serological Screening: Which Shall We Select?

PURPOSE: We retrospectively analyzed the results of prenatal diagnosis in women with high-risk (HR) serological screening results, and discussed the reasonable application of diagnostic testing. PATIENTS AND METHODS: Diagnostic testing was done in 2239 pregnant women who had HR results from serological screening in two prenatal diagnosis centers. According to the HR results, they were divided into simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups. After receiving counselling from clinicians, they were allowed to choose either the traditional karyotype analysis and/or chromosomal microarray analysis (CMA). RESULTS: Those who underwent CMA comprised 49.3%, 97.6%, and 100% of the HR group, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. Among the 100 (4.47%) clinically significant results, 55 (2.46%), 15 (0.67%), and 30 (1.34%) were chromosomal aneuploidies, chromosomal structural abnormalities, and pathogenic copy number variations (CNVs), respectively. The rate of abnormalities was 3.77%, 13.71%, and 19.05% in the simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. The increasing rate of clinical pathogenic CNVs was 1.34% using CMA in HR pregnant women, 9.52% in the HR combined with other indication group, and 1.24% in the simple HR group. Among the 573 women who chose both diagnostic tests, 45 had abnormal results. Only one case detected using karyotype analysis was missed on CMA. The incidence of chromosomal aneuploidy tended to increase with increase in HR values. However, chromosomal structural abnormalities and pathogenic CNVs did not increase. CONCLUSION: CMA should be recommended as the first-line diagnostic testing for women with HR screening results, especially combined with other abnormal indications.

Unveiling Extreme Photoreduction Potentials of Donor-Acceptor Cyanoarenes to Access Aryl Radicals from Aryl Chlorides.

Since the seminal work of Zhang in 2016, donor-acceptor cyanoarene-based fluorophores, such as 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN), have been widely applied in photoredox catalysis and used as excellent metal-free alternatives to noble metal Ir- and Ru-based photocatalysts. However, all the reported photoredox reactions involving this chromophore family are based on harnessing the energy from a single visible light photon, with a limited range of redox potentials from -1.92 to +1.79 V vs SCE. Here, we document the unprecedented discovery that this family of fluorophores can undergo consecutive photoinduced electron transfer (ConPET) to achieve very high reduction potentials. One of the newly synthesized catalysts, 2,4,5-tri(9H-carbazol-9-yl)-6-(ethyl(phenyl)amino)isophthalonitrile (3CzEPAIPN), possesses a long-lived (12.95 ns) excited radical anion form, 3CzEPAIPN•-*, which can be used to activate reductively recalcitrant aryl chlorides (Ered ≈ -1.9 to -2.9 V vs SCE) under mild conditions. The resultant aryl radicals can be engaged in synthetically valuable aromatic C-B, C-P, and C-C bond formation to furnish arylboronates, arylphosphonium salts, arylphosphonates, and spirocyclic cyclohexadienes.

Incidence and Outcomes of Acute Kidney Injury in Patients Admitted to Hospital With COVID-19: A Retrospective Cohort Study.

BACKGROUND: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. OBJECTIVE: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. DESIGN: Retrospective cohort study from a registry of patients with COVID-19. SETTING: Three community and 3 academic hospitals. PATIENTS: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. MEASUREMENTS: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. METHODS: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. RESULTS: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). LIMITATIONS: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. CONCLUSIONS: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. TRIAL REGISTRATION: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Ectopic Expression of GhSAMDC3 Enhanced Salt Tolerance Due to Accumulated Spd Content and Activation of Salt Tolerance-Related Genes in Arabidopsis thaliana.

Polyamines (PAs), especially spermidine and spermine (which are involved in various types of abiotic stress tolerance), have been reported in many plant species. In this study, we identified 14 putative S-adenosylmethionine decarboxylase genes (GhSAMDC1-14) in upland cotton. Based on phylogenetic and expression analyses conducted under different abiotic stresses, we selected and transferred GhSAMDC3 into Arabidopsis thaliana. Compared to the wild type, transgenic plants displayed rapid growth and increases in average leaf area and leaf number of 52% and 36%, respectively. In transgenic plants, the germination vigor and rate were markedly enhanced under NaCl treatment, and the plant survival rate increased by 50% under 300 mM NaCl treatment. The spermidine content was significantly increased, possibly due to the synthesis of a series of PAs and oxidant and antioxidant genes, resulting in improved salinity tolerance in Arabidopsis. Various salinity resistance-related genes were upregulated in transgenic plants. Together, these results indicate that ectopic expression of GhSAMDC3 raised salinity tolerance by the accumulation of spermidine and activation of salinity tolerance-related genes in A. thaliana.

[Application of chromosomal microarray analysis in prenatal diagnosis of pregnant women with advanced age].

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age. METHODS: CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed. RESULTS: Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and <35 and between those with age factor only and with additional indications (P> 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect. CONCLUSION: There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.