Altered chromatin topologies caused by balanced chromosomal translocation lead to central iris hypoplasia.

Despite the advent of genomic sequencing, molecular diagnosis remains unsolved in approximately half of patients with Mendelian disorders, largely due to unclarified functions of noncoding regions and the difficulty in identifying complex structural variations. In this study, we map a unique form of central iris hypoplasia in a large family to 6q15-q23.3 and 18p11.31-q12.1 using a genome-wide linkage scan. Long-read sequencing reveals a balanced translocation t(6;18)(q22.31;p11.22) with intergenic breakpoints. By performing Hi-C on induced pluripotent stem cells from a patient, we identify two chromatin topologically associating domains spanning across the breakpoints. These alterations lead the ectopic chromatin interactions between APCDD1 on chromosome 18 and enhancers on chromosome 6, resulting in upregulation of APCDD1. Notably, APCDD1 is specifically localized in the iris of human eyes. Our findings demonstrate that noncoding structural variations can lead to Mendelian diseases by disrupting the 3D genome structure and resulting in altered gene expression.

Clinical features of patients with mutations in genes for nanophthalmos.

BACKGROUND/AIMS: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 (PRSS56), membrane-type frizzled-related protein (MFRP), myelin regulatory factor (MYRF) and transmembrane protein 98 (TMEM98) and to evaluate the association between angle-closure glaucoma (ACG) and NNO. METHODS: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis. RESULTS: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP. Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma. CONCLUSION: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling.

Review on Phase Synchronization Methods for Spaceborne Multistatic Synthetic Aperture Radar.

Multistatic synthetic aperture radar (SAR) is a special mode of SAR system. The radar transmitter and receiver are located on different satellites, which brings many advantages, such as flexible baseline configuration, diverse receiving modes, and more detailed ground object classification information. The multistatic SAR has been widely used in interferometry, moving target detection, three-dimensional imaging, and other fields. The frequency offset between different oscillators will cause a modulation phase error in the signal. Therefore, phase synchronization is one of the most critical problems to be addressed in distributed SAR systems. This article reviews phase synchronization techniques, which are mainly divided into two methods: synchronization by direct microwave link and synchronization by a data-based estimation algorithm. Furthermore, the future development of synchronization technology is anticipated.

Mechanism of acoustic pressure spectrum shifting toward lower frequencies in applied current thermoacoustic imaging.

Objective. Thermoacoustic tomography (TAT) is a promising imaging technique used for early cancer diagnosis, tumor therapy, animal study and brain imaging. Although it is widely known that the TAT frequency response depends on the pulse width of the source and the size of the object, a thorough comprehension of the quantitative frequency modulation in TAT and the mechanism governing the shift in the thermoacoustic pressure spectrum towards lower frequencies with respect to the excitation source is still lacking. This study aims to understand why the acoustic pressure spectrum and the final voltage signals shift towards lower frequencies in TAT.Approach. We employed a linear time-invariant model. In the proposed model, the applied current thermoacoustic imaging (ACTAI) process is divided into the thermoacoustic stage and the acoustoelectric stage. These two stages are characterized by the thermoacoustic transfer function(TATF) and the transducer transfer function (TDTF), respectively. We confirmed the effectiveness of our model through a rigorous examination involving both simulations and experiments.Main results. Simulation results indicate that the TATF behaves as a low-pass filter. The inherent low-pass nature induces a shift towards low frequencies in the acoustic pressure spectrum. Experiments further confirm this behavior, demonstrating that the final electrical voltage also shifts towards low frequencies. Notably, employing the proposed model, there is a remarkable consistency between the main frequency bands of the synthesized and measured final voltage spectrum.Significance. The proposed model thoroughly explains how the TATF causes shifts to low frequencies in both the acoustic pressure spectrum and the final voltage spectrum in TAT. These insights deepen our understanding of optimizing TAT systems in the frequency domain, including aspects like filter design and transducer selection. Furthermore, we underscore the potential significance of this discovery for medical applications, particularly in the context of cancer diagnosis.

Confined DNA tetrahedral molecular sieve for size-selective electrochemiluminescence sensing.

Size selectivity is crucial in highly accurate preparation of biosensors. Herein, we described an innovative electrochemiluminescence (ECL) sensing platform based on the confined DNA tetrahedral molecular sieve (DTMS) for size-selective recognition of nucleic acids and small biological molecule. Firstly, DNA template (T) was encapsulated into the inner cavity of DNA tetrahedral scaffold (DTS) and hybridized with quencher (Fc) labeled probe DNA to prepare DTMS, accordingly inducing Ru(bpy)32+ and Fc closely proximate, resulting the sensor in a "signal-off" state. Afterwards, target molecules entered the cavity of DTMS to realize the size-selective molecular recognition while prohibiting large molecules outside of the DTMS, resulting the sensor in a "signal-on" state due to the release of Fc. The rigid framework structure of DTS and the anchor of DNA probe inside the DTS effectively avoided the nuclease degradation of DNA probe, and nonspecific protein adsorption, making the sensor possess potential application prospect for size-selective molecular recognition in diagnostic analysis with high accuracy and specificity.

Quantitative assessment of retinochoroidal microvasculature in patients with carotid artery stenosis using OCT angiography.

PURPOSE: To investigate the alterations in retinochoroidal parameters measured by optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with carotid artery stenosis (CAS) and assess their associations with digital subtraction angiography (DSA) data. METHOD: This study enrolled patients diagnosed with CAS and age-matched healthy controls. Both groups underwent OCT and OCTA examinations. DSA and assessment of carotid artery stenosis were performed only in the CAS group. The study evaluated various retinochoroidal parameters from OCT and OCTA, including linear vessel density (LVD), foveal avascular zone (FAZ), choroidal thickness (ChT), and retinal nerve fiber layer (RNFL) thickness. DSA-derived measures included cervical segment (C1) diameter, cavernous segment (C4) diameter, stenosis percentage, ophthalmic artery (OA) filling time, C1-OA filling time, and residual stenosis. RESULTS: A total of 42 eyes from 30 CAS patients and 60 eyes from 30 healthy controls were included. Patients with CAS displayed significantly decreased LVD compared to controls (p < 0.001). Additionally, the CAS group had thinner choroid and RNFL (p = 0.047 and p < 0.001, respectively). Macular LVD negatively correlated with both stenosis percentage and C1-OA filling time (p = 0.010 and p = 0.014, respectively). In patients who underwent carotid artery stenting, preoperative ChT significantly correlated with residual stenosis (Pearson r = -0.480, p = 0.020). CONCLUSION: OCT and OCTA provide a quantitative assessment of retinochoroidal microstructural changes associated with CAS, suggesting potential for noninvasive evaluation of the disease. This might contribute to the prevention of irreversible ocular complications and early detection of CAS. Furthermore, ChT may not only aid in diagnosing CAS more reliably but also offer prognostic information.

Datasets-Based IMPDH1 Revisited: Heterozygous Missense Variants for Dominant Retinitis Pigmentosa While Truncation Variants Are Likely Non-Pathogenic.

PURPOSE: Heterozygous variants of IMPDH1 are associated with autosomal dominant retinitis pigmentosa (adRP). The current study aims to investigate the characteristics of the adRP-associated variants. METHODS: IMPDH1 variants from our exome sequencing dataset were retrieved and systemically evaluated through multiple online prediction tools, comparative genomics (in-house dataset, HGMD, and gnomAD), and phenotypic association. Potential pathogenic variants (PPVs) were further confirmed by Sanger sequencing and segregation analysis. RESULTS: In total, seven heterozygous PPVs (six missenses and one inframe) were identified in 10 families with RP, in which six of the seven might be classified as pathogenic or likely pathogenic while one others as variants of uncertain significance. IMPDH1 variants contributed to 0.7% (10/1519) of RP families in our cohort, ranking the top four genes implicated in adRP. These adRP-associated variants were located in exons 8-10, a region within or downstream of the CBS domain. All these variants were predicted to be damaged by at least three of the six online prediction tools. Two truncation variants were considered non-pathogenic. Hitherto, 41 heterozygous variants of IMPDH1 were detected in 110 families in published literature, including 33 missenses, two inframes, and six truncations (including a synonymous variant affecting splicing). Of the 35 missense and inframe variants, most were clustered in exons 8-10 (77.1%, 27/35), including 18 (51.4%, 18/35) in exon 10 accounting for 70.9% (78/110) of the families. However, truncation variants were enriched in the general population with a pLI value of 0 (tolerated), and the reported variants in patients with RP did not cluster in specific region. CONCLUSIONS: Our data together with comprehensive analysis of existing datasets suggest that causative variants of IMPDH1 are usually missense and mostly clustered in exons 8-10. Conversely, most missense variants outside this region and truncation variants should be interpreted with great care in clinical gene test.

Variant and clinical landscape of Leber hereditary optic neuropathy based on 1516 families with mtDNA variants in a tertiary centre.

AIMS: To investigate the clinical characteristics of Leber hereditary optic neuropathy (LHON) with mtDNA primary mutations to better understand features associated with prognosis. METHODS: This study enrolled 1540 LHON patients from 1516 unrelated families genetically confirmed by Sanger or whole-mitochondrial sequencing between 1997 and 2022. The spectrum of variants was summarised and compared in different ethnic groups. Clinical data from outpatients were collected, including onset age, disease course, optic disc categories and the corresponding visual acuity. RESULTS: Of the 1516 LHON families, 13 pathogenic mtDNA variants were detected, in which the proportion of m.11778G>A, m.3460G>A and m.3635G>A was significantly different from non-East Asians (p<0.0001). About 95% (1075/1131) of patients were between 8 and 40 years old at onset, with a median onset age of 16. The eyes of m.14484T>C patients presented with better visual acuity and slower progression across patients with different onset ages and initial severity. Eyes (N=439) with available fundus images were divided into four categories (C1-C4). The progression grades were derived from the category and the corresponding time course, where a higher grade (C3-C4 within 1 year) was associated with greater visual impairment than a lower grade (C1-C2 over 1 year) (p=4.60E-05) . A prognostic matrix showed that later onset and a higher progression grade are associated with higher risk of blindness. CONCLUSION: Compared with non-East Asians, Chinese LHON patients had higher proportions of m.11778G>A and m.3635G>A and lower m.3460G>A mutations. A novel progression grade derived from optic disc category was proposed. The prognostic matrix indicated that lower grade and younger-onset age are the most favourable prognostic factors.

Effectiveness of immune checkpoint inhibitors in combination with tyrosine kinase inhibitors in patients with advanced or metastatic colorectal carcinoma with either mismatch repair proficient or metastatic microsatellite stable disease: A systematic review and meta­analysis.

Immune checkpoint inhibitors (ICIs) have limited efficacy in mismatch repair proficient (pMMR) or metastatic microsatellite stable (MSS) advanced or metastatic colorectal cancer (mCRC). ICIs, in conjunction with tyrosine kinase inhibitors (TKIs) possessing anti-angiogenic properties, serve as a potential strategy for circumventing the resistance exhibited by MSS or pMMR mCRC to immunotherapeutic interventions. The present study aimed to evaluate efficacy and safety of ICIs + TKIs and provide a reference for the treatment of CRC. The present systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, Cochrane, Web of Science and ClinicalTrials.gov databases were screened from January 1, 2003 to July 28, 2023. A total of 14 studies were included in qualitative and quantitative analyses, with a total of 819 patients enrolled. The Newcastle-Ottawa scale scores of the 14 cohort studies included were ≥7, indicating they were of a high quality. The objective response rate (ORR) of ICIs + TKIs was 14% [95% confidence interval (CI), 0.08-0.24; P=0.132] in patients with advanced or metastatic MSS/pMMR CRC. The disease control rate (DCR) was 65% (95% CI, 0.58-0.74; P<0.0001). The overall incidence of adverse events of varying severity linked to combination of ICIs and TKIs in patients with advanced or metastatic MSS/pMMR CRC was 64% (95% CI, 0.52-0.78; P<0.0001). The incidence of grade ≥3 adverse reactions was 24% (95% CI, 0.14-0.4; P<0.0001). The sensitivity analysis indicated that the exclusion of individual studies did not yield statistically significant variations in combined analysis results. Based on the examination of publication bias, ORR and DCR, Begg's and Egger's tests had P-values of 0.114 and 0.395, respectively. Overall publication bias overall was absent in the Begg's funnel plot, as there was no apparent asymmetry. Nonetheless, the P-values of the Egger's and Begg's tests for adverse reactions and adverse reactions grade ≥3 were P=0.008 and P=0.048, respectively. The asymmetry of the Begg's funnel plots was evident, suggesting the presence of potential publication bias regarding adverse event results. In conclusion, the combination of ICIs and TKIs demonstrates a favorable effectiveness and notable safety profile in the management of patients with advanced or metastatic MSS/pMMR CRC.

Clinical and Genetic Landscape of Ectopia Lentis Based on a Cohort of Patients From 156 Families.

Purpose: To extend the mutation spectrum and explore the characteristics of genotypes and ocular phenotypes in ectopia lentis (EL). Methods: Variants in all 14 reported EL-associated genes were selected from in-house data sets as well as literature review, and available clinical data were analyzed. Results: Likely pathogenic variants in three genes were identified in 156 unrelated families with EL from the in-house cohort, of which 97.4% resulted from variants in FBN1, whereas the remaining were caused by variants in ADAMTSL4 (1.3%) and LTBP2 (1.3%). A comparative analysis of the in-house data and literature review suggested several characteristics: (1) a higher proportion of cysteine involvement variants in FBN1, either variants introducing or eliminating cysteine, and an earlier diagnosis age were presented in our cohort than in published literature; (2) the axial length (AL) and refractive error increased more rapidly with age in preschool EL children than normal children, and the increased rate of AL was slower in patients with surgery than those without surgery; (3) aberrant astigmatism was common in EL; and (4) worse vision and earlier onset age were observed in patients with non-FBN1 variants (all P < 0.05). Conclusions: Variants in FBN1 are the predominant cause of EL, with the most common cysteine involvement variants. Early-stage EL manifests refractive error but gradually converts to axial myopia through defocus introduced by lens dislocation. Aberrant astigmatism is a suggestive sign of EL. Non-FBN1 variants cause early-onset and severe phenotypes. These results provide evidence for early diagnosis as well as timely treatment for EL.

Comparison of enteral immunonutrition and enteral nutrition in patients undergoing gastric cancer surgery: a systematic review and meta-analysis of randomized, controlled trials.

OBJECTIVE: Enteral immunonutrition is a nutritional intervention that has been studied in postoperative patients with gastric cancer, but its effectiveness is controversial. This study aimed to investigate the effects of enteral immunonutrition and enteral nutrition on immune function in patients who undergo gastric cancer surgery. METHODS: We performed a systematic review and meta-analysis. A comprehensive search was conducted in PubMed, Embase, Cochrane, Web of Knowledge, and ClinicalTrials.gov from the inception of the review until 10 March 2023. Twelve studies were included for qualitative and quantitative analyses. RESULTS: We studied 1124 patients, including 565 patients in the enteral immunonutrition group and 559 in the enteral nutrition (controls) group. All included randomized, controlled trials were high quality. CD4+ levels, lymphocytes, transferrin concentrations, and systemic inflammatory response syndrome were not significantly different between the enteral immunonutrition and enteral nutrition groups. However, CD8+, immunoglobulins G and M, and proalbumin concentrations, CD4+/CD8+, and infectious complications were significantly higher in the enteral immunonutrition group than in the enteral nutrition group. A sensitivity analysis showed consistent results after excluding each study. Begg's test showed no publication bias. CONCLUSIONS: Enteral immunonutrition is an effective nutritional intervention that improves immune function in patients who have undergone gastric cancer surgery.

Clinical and genetic risk factors underlying severe consequence identified in 75 families with unilateral high myopia.

BACKGROUNDS: Unilateral high myopia (uHM), commonly observed in patients with retinal diseases or only with high myopia, is frequently associated with amblyopia with poor prognosis. This study aims to reveal the clinical and genetic spectrum of uHM in a large Chinese cohort. METHODS: A total of 75 probands with simplex uHM were included in our Pediatric and Genetic Eye Clinic. Patients with significant posterior anomalies other than myopic fundus changes were excluded. Variants were detected by exome sequencing and then analyzed through multiple-step bioinformatic and co-segregation analysis and finally confirmed by Sanger sequencing. Genetic findings were correlated with associated clinical data for analysis. RESULTS: Among the 75 probands with a mean age of 6.21 ± 4.70 years at the presentation, myopic fundus of C1 and C2 was observed in 73 (97.3%) probands. Surprisingly, specific peripheral changes were identified in 63 eyes involving 36 (48.0%) probands after extensive examination, including peripheral retinal avascular zone (74.6%, 47/63 eyes), neovascularization (54.0%), fluorescein leakage (31.7%), peripheral pigmentary changes (31.7%), and others. Exome sequencing identified 21 potential pathogenic variants of 13 genes in 20 of 75 (26.7%) probands, including genes for Stickler syndrome (COL11A1 and COL2A1; 6/20), FEVR (FZD4, LRP5, and TSPAN12; 5/20), and others (FBN1, GPR179, ZEB2, PAX6, GPR143, OPN1LW, FRMD7, and CACNA1F; 9/20). For the peripheral retinal changes in the 20 probands, variants in Stickler syndrome-related genes were predominantly associated with retinal pigmentary changes, lattice degeneration, and retinal avascular region, while variants in genes related to FEVR were mainly associated with the avascular zone, neovascularization, and fluorescein leakage. CONCLUSIONS: Genetic defects were identified in about one-fourth of simplex uHM patients in which significant consequences may be hidden under a classic myopic fundus in up to half. To our knowledge, this is the first systematic genetic study on simplex uHM to date. In addition to routine care of strabismus and amblyopia, careful examination of the peripheral retina and genetic screening is warranted for patients with uHM in order to identify signs of risk for retinal detachment and other complications and provide meaningful genetic counseling.

Real-world use of inotuzumab ozogamicin is associated with lower health care costs than blinatumomab in patients with acute lymphoblastic leukemia in the first relapsed/refractory setting.

Aim: To compare all-cause and acute lymphoblastic leukemia (ALL)-related healthcare resource utilization (HCRU) and costs among patients receiving inotuzumab ozogamicin (InO) and blinatumomab (Blina) for ALL in the first relapsed/refractory (R/R) setting. Patients & methods: We studied retrospective claims for adult commercial and Medicare Advantage enrollees with ALL receiving InO (n = 29) or Blina (n = 23) from 1 January 2015 to 16 February 2021. Mean per-patient-per-month (PPPM) HCRU and total costs were described and multivariable-adjusted PPPM total all-cause and ALL-related predicted costs were calculated. Results: Mean monthly ALL-related hospitalizations were the same for patients receiving InO and Blina (PPPM = 0.8 stays); however, the length of ALL-related hospital stay was almost twice as long among patients receiving Blina versus InO (ALL-related: InO = 7.6 days; Blina = 14.1 days; p = 0.346). In multivariable models, total ALL-related costs were 43% lower for InO compared with Blina (PPPM costs: InO = $93,767; Blina = $163,470; p = 0.021). Conclusion: In the first R/R setting, patients who used InO had significantly lower all-cause and ALL-related costs compared with patients who used Blina, in part driven by hospitalization patterns.

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II).

INTRODUCTION: Percutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses, FFR resulted in fewer coronary interventions and was non-inferior to IVUS with respect to clinical outcomes. However, whether this finding can be applied to angiography-derived FFR in significant coronary artery disease (CAD) remains unclear. METHOD AND ANALYSIS: The comparison of angiography-derived FFR-guided and IVUS-guided intervention strategies for clinical outcomes in patients with coronary artery disease (FLAVOUR II) trial is a multicentre, prospective, randomised controlled trial. A total of 1872 patients with angiographically significant CAD (stenoses of at least 50% as estimated visually through angiography) in a major epicardial coronary artery will be randomised 1:1 to receive either angiography-derived FFR-guided or IVUS-guided PCI. Patients will be treated with second-generation drug-eluting stent according to the predefined criteria for revascularisation: angiography-derived FFR≤0.8 and minimal lumen area (MLA)≤3 mm2 or 3 mm270%. The primary endpoint is a composite of all-cause death, myocardial infarction and revascularisation at 12 months after randomisation. We will test the non-inferiority of the angiography-derived FFR-guided strategy compared with the IVUS-guided decision for PCI and the stent optimisation strategy.The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD. ETHICS AND DISSEMINATION: FLAVOUR II was approved by the institutional review board at each participating site (The Second Affiliated Hospital of Zhejiang University School of Medicine Approval No: 2020LSYD410) and will be conducted in line with the Declaration of Helsinki. Informed consent would be obtained from each patient before their participation. The study results will be submitted to a scientific journal. TRIAL REGISTRATION NUMBER: NCT04397211.

Retinopathy as an initial sign of hereditary immunological diseases: report of six families and challenges in eye clinic.

Introduction: Retinal degenerative or inflammatory changes may occur with hereditary immunological disorders (HID) due to variants in approximately 20 genes. This study aimed to investigate if such retinopathy may present as an initial sign of immunological disorders in eye clinic. Methods: The variants in the 20 genes were selected from in-house exome sequencing data from 10,530 individuals with different eye conditions. Potential pathogenic variants were assessed by multistep bioinformatic analysis. Pathogenic variants were defined according to the ACMG/AMP criteria and confirmed by Sanger sequencing, co-segregation analysis, and consistency with related phenotypes. Ocular clinical data were thoroughly reviewed, especially fundus changes. Results: A total of seven pathogenic variants in four of the 20 genes were detected in six probands from six families, including three with hemizygous nonsense variants p.(Q308*), p.(Q416*), and p.(R550*) in MSN, one with homozygous nonsense variants p.(R257*) in AIRE, one with compound heterozygous nonsense variants p.(R176*) and p.(T902*) in LAMB2, and one with a known c.1222T>C (p.W408R) heterozygous variant in CBL. Ocular presentation, as the initial signs of the diseases, was mainly retinopathy mimicking other forms of hereditary retinal degeneration, including exudative vitreoretinopathy in the three patients with MSN variants or tapetoretinal degeneration in the other three patients. Neither extraocular symptoms nor extraocular manifestations were recorded at the time of visit to our eye clinic. However, of the 19 families in the literature with retinopathy caused by variants in these four genes, only one family with an AIRE homozygous variant had retinopathy as an initial symptom, while the other 18 families had systemic abnormalities that preceded retinopathy. Discussion: This study, for the first time, identified six unrelated patients with retinopathy as their initial and only presenting sign of HID, contrary to the previous reports where retinopathy was the accompanying sign of systemic HID. Recognizing such phenotype of HID may facilitate the clinical care of these patients. Follow-up visits to such patients and additional studies are expected to validate and confirm our findings.

Effects of phosphine ligands in nickel-catalyzed decarbonylation reactions of lactone.

Due to the ubiquity of carbonyl compounds and the abundance of nickel on the earth, nickel-catalyzed decarbonylation has garnered increasing attention in recent years. This type of reaction has seen significant developments in various aspects; however, certain challenges concerning reactivity, selectivity, and transformation efficiency remain pressing and demand urgent resolution. In this study, we employed DFT calculations to investigate the mechanism of nickel-catalyzed decarbonylation reactions involving lactones, as well as the effects of phosphine ligands. Mechanically, Ni(0) first activates the C(acyl)-O bond of the lactone, followed by a decarbonylation step, and ultimately results in reductive elimination under carbonyl coordination to yield the product. Through a comprehensive examination of the electronic and steric effects of the phosphine ligands, we deduced that the electronic effect of the ligand plays a dominant role in the decarbonylation reaction. By enhancing the electron-withdrawing ability of the ligand, the energy barrier of the entire reaction can be significantly reduced. The obtained insights should be valuable for understanding the detailed mechanism and the role of phosphine ligands in nickel catalysis. Moreover, they offer crucial clues for the rational design of more efficient catalytic reactions.

Sex Differences in Fractional Flow Reserve- or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: A recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations. OBJECTIVES: This study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies. METHODS: In this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: Of 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies. CONCLUSIONS: In cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men.

Clinical and Genetic Features of NR2E3-Associated Retinopathy: A Report of Eight Families with a Longitudinal Study and Literature Review.

(1) Background: NR2E3 encodes a nuclear receptor transcription factor that is considered to promote cell differentiation, affect retinal development, and regulate phototransduction in rods and cones. This study aimed to analyze the clinical characteristics and observe the prognosis of autosomal dominant retinopathy (ADRP) and autosomal recessive retinopathy (ARRP) associated with NR2E3; (2) Methods: NR2E3 variants were collected from our exome sequencing data and identified per the American College of Medical Genetics and Genomics criteria. Data from our cohort and a systemic literature review were conducted to explore the NR2E3 variants spectrum and potential genotype-phenotype correlations; (3) Results: Nine pathogenic variants/likely pathogenic variants in NR2E3, including five novel variants, were detected in eight families (four each with ADRP and ARRP). Follow-up data showed schisis/atrophy in the macula and retinal degeneration initiation around the vascular arcades with differences in ADRP and ARRP. A systemic literature review indicated patients with ADRP presented better visual acuity (p < 0.01) and later onset age (p < 0.0001) than did those with ARRP; (4) Conclusions: Macular schisis and retinal degeneration around vascular arcades may present as the prognosis of NR2E3-retinopathy, dominant, or recessive. Our data might further enrich our understanding of NR2E3 variants and associated inherited retinopathy.

Unraveling the mechanism of increased synthesis of hydrogen from an anaerobic fermentation by zinc ferrate nanoparticles: Mesophilic and thermophilic situations comparison.

In this work, ZnFe2O4 NPs were created using the pyrolysis process, and its effects on thermophilic (TF) and mesophilic (MF) fermentation were examined. In MF, the maximum hydrogen yield (MHY) occurred in the 50 mg/L ZnFe2O4 NPs group (228.01 mL/g glucose), which was 45.24% higher than that of the control group (157.01 mL/g glucose). While in TF, MHY appeared in 100 mg/L ZnFe2O4 NPs was 149.12 mL/g glucose, which was 38.83% higher than the control group (107.41 mL/g glucose). ZnFe2O4 NPs boosted the synthesis of ferredoxin, hydrogenase, and ethanol dehydrogenase by increasing the generation of butyrate in MF and acetate in TF. Moreover, Clostridium sensu stricto 5 and 10 in MF and TF rose by 9.20% and 9.40%, respectively, due to the increased abundance of predominant hydrogen-producing bacteria by ZnFe2O4 NPs.

Non-Pharmaceutical Interventions against COVID-19 Causing a Lower Trend in Age of LHON Onset.

Leber hereditary optic neuropathy (LHON) is a monogenic but multifactorial disease vulnerable to environmental triggers. Little is known about how LHON onset changed during the COVID-19 pandemic and how non-pharmaceutical interventions (NPHIs) against COVID-19 impact LHON onset. One hundred and forty-seven LHON patients with the m.11778G>A mutation complaining of vision loss were involved between January 2017 and July 2022. The onset time points, age of onset, and possible risk factors were evaluated. Analyses were conducted among 96 LHON patients in the Pre-COVID-19 group and 51 in the COVID-19 group. The median (IQR) age of onset decreased significantly from 16.65 (13.739, 23.02) in pre-COVID-19 to 14.17 (8.87, 20.29) during COVID-19. Compared with the Pre-COVID-19 group, the COVID-19 group exhibited bimodal distribution with an additional peak at six; the first quarter of 2020 also witnessed a relatively denser onset, with no subsequent second spike. NPHIs against COVID-19 significantly changed patients' lifestyles, including higher secondhand smoke exposure (p < 0.001), adherence to masks (p < 0.001), reduction in time spent outdoors for leisure (p = 0.001), and prolonged screen time (p = 0.007). Multivariate logistic regression revealed that secondhand smoke exposure and mask-wearing were independent risk factors of younger LHON onset. Lower age of onset of LHON appeared after the breakout of the COVID-19 pandemic, and novel risk factors were detected, including secondhand exposure and long mask-wearing. Carriers of LHON mtDNA mutations, especially teenagers or children, should be advised to avoid secondhand smoke exposure and there are possible adverse outcomes of longer mask-wearing.