Control and single-shot readout of an ion embedded in a nanophotonic cavity.

Distributing entanglement over long distances using optical networks is an intriguing macroscopic quantum phenomenon with applications in quantum systems for advanced computing and secure communication1,2. Building quantum networks requires scalable quantum light-matter interfaces1 based on atoms3, ions4 or other optically addressable qubits. Solid-state emitters5, such as quantum dots and defects in diamond or silicon carbide6-10, have emerged as promising candidates for such interfaces. So far, it has not been possible to scale up these systems, motivating the development of alternative platforms. A central challenge is identifying emitters that exhibit coherent optical and spin transitions while coupled to photonic cavities that enhance the light-matter interaction and channel emission into optical fibres. Rare-earth ions in crystals are known to have highly coherent 4f-4f optical and spin transitions suited to quantum storage and transduction11-15, but only recently have single rare-earth ions been isolated16,17 and coupled to nanocavities18,19. The crucial next steps towards using single rare-earth ions for quantum networks are realizing long spin coherence and single-shot readout in photonic resonators. Here we demonstrate spin initialization, coherent optical and spin manipulation, and high-fidelity single-shot optical readout of the hyperfine spin state of single 171Yb3+ ions coupled to a nanophotonic cavity fabricated in an yttrium orthovanadate host crystal. These ions have optical and spin transitions that are first-order insensitive to magnetic field fluctuations, enabling optical linewidths of less than one megahertz and spin coherence times exceeding thirty milliseconds for cavity-coupled ions, even at temperatures greater than one kelvin. The cavity-enhanced optical emission rate facilitates efficient spin initialization and single-shot readout with conditional fidelity greater than 95 per cent. These results showcase a solid-state platform based on single coherent rare-earth ions for the future quantum internet.

Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.

In Parkinson's disease (PD), reduced dopamine levels in the basal ganglia have been associated with altered neuronal firing and motor dysfunction. It remains unclear whether the altered firing rate or pattern of basal ganglia neurons leads to parkinsonism-associated motor dysfunction. In the present study, we show that increased histaminergic innervation of the entopeduncular nucleus (EPN) in the mouse model of PD leads to activation of EPN parvalbumin (PV) neurons projecting to the thalamic motor nucleus via hyperpolarization-activated cyclic nucleotide-gated (HCN) channels coupled to postsynaptic H2R. Simultaneously, this effect is negatively regulated by presynaptic H3R activation in subthalamic nucleus (STN) glutamatergic neurons projecting to the EPN. Notably, the activation of both types of receptors ameliorates parkinsonism-associated motor dysfunction. Pharmacological activation of H2R or genetic upregulation of HCN2 in EPNPV neurons, which reduce neuronal burst firing, ameliorates parkinsonism-associated motor dysfunction independent of changes in the neuronal firing rate. In addition, optogenetic inhibition of EPNPV neurons and pharmacological activation or genetic upregulation of H3R in EPN-projecting STNGlu neurons ameliorate parkinsonism-associated motor dysfunction by reducing the firing rate rather than altering the firing pattern of EPNPV neurons. Thus, although a reduced firing rate and more regular firing pattern of EPNPV neurons correlate with amelioration in parkinsonism-associated motor dysfunction, the firing pattern appears to be more critical in this context. These results also confirm that targeting H2R and its downstream HCN2 channel in EPNPV neurons and H3R in EPN-projecting STNGlu neurons may represent potential therapeutic strategies for the clinical treatment of parkinsonism-associated motor dysfunction.

Cell Membrane Tension Gradients, Membrane Flows, and Cellular Processes.

Cell membrane tension affects and is affected by many fundamental cellular processes, yet it is poorly understood. Recent experiments show that membrane tension can propagate at vastly different speeds in different cell types, reflecting physiological adaptations. Here we briefly review the current knowledge about membrane tension gradients, membrane flows, and their physiological context.

The genome of Lespedeza potaninii reveals biased subgenome evolution and drought adaptation.

Lespedeza potaninii, a xerophytic subshrub belonging to the legume family, is native to the Tengger Desert and is highly adapted to drought. It has important ecological value due to its drought adaptability, but the underlying molecular mechanisms remain largely unknown. Here, we report a 1.24 Gb chromosome-scale assembly of the L. potaninii genome (contig N50=15.75 Mb). Our results indicate that L. potaninii underwent an allopolyploid event with two subgenomes, A and B, presenting asymmetric evolution and B subgenome dominance. We estimate that the two diploid progenitors of L. potaninii diverged around 3.6 MYA and merged around 1.0 MYA. We revealed that the expansion of hub genes associated with drought responses, such as the binding partner 1 of accelerated cell death 11 (ACD11) (BPA1), facilitated environmental adaptations of L. potaninii to desert habitats. We found a novel function of the BPA1 family in abiotic stress tolerance in addition to the known role in regulating the plant immune response, which could improve drought tolerance by positively regulating reactive oxygen species homeostasis in plants. We revealed that bZIP transcription factors could bind to the BPA1 promoter and activate its transcription. Our work fills the genomic data gap in the Lespedeza genus and the tribe Desmodieae, which should provide both theoretical support in the study of drought tolerance and in the molecular breeding of legume crops.

Role of HCN channels in the functions of basal ganglia and Parkinson's disease.

Parkinson's disease (PD) is a motor disorder resulting from dopaminergic neuron degeneration in the substantia nigra caused by age, genetics, and environment. The disease severely impacts a patient's quality of life and can even be life-threatening. The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel is a member of the HCN1-4 gene family and is widely expressed in basal ganglia nuclei. The hyperpolarization-activated current mediated by the HCN channel has a distinct impact on neuronal excitability and rhythmic activity associated with PD pathogenesis, as it affects the firing activity, including both firing rate and firing pattern, of neurons in the basal ganglia nuclei. This review aims to comprehensively understand the characteristics of HCN channels by summarizing their regulatory role in neuronal firing activity of the basal ganglia nuclei. Furthermore, the distribution and characteristics of HCN channels in each nucleus of the basal ganglia group and their effect on PD symptoms through modulating neuronal electrical activity are discussed. Since the roles of the substantia nigra pars compacta and reticulata, as well as globus pallidus externus and internus, are distinct in the basal ganglia circuit, they are individually described. Lastly, this investigation briefly highlights that the HCN channel expressed on microglia plays a role in the pathological process of PD by affecting the neuroinflammatory response.

Multicountry Review of Streptococcus pneumoniae Serotype Distribution Among Adults With Community-Acquired Pneumonia.

BACKGROUND: Nonbacteremic community-acquired pneumonia (CAP) is a leading presentation of severe pneumococcal disease in adults. Serotype-specific urinary antigen detection (UAD) assay can detect serotypes causing pneumococcal CAP, including nonbacteremic cases, and guide recommendations for use of higher valency pneumococcal conjugate vaccines (PCVs). METHODS: Adult CAP serotype distribution studies that used both Pfizer UADs (UAD1, detects PCV13 serotypes; UAD2, detects PCV20 non-PCV13 serotypes plus 2, 9N, 17F, and 20) were identified by review of an internal study database and included if results were published. The percentages of all-cause radiologically confirmed CAP (RAD + CAP) due to individual or grouped (PCV13, PCV15, and PCV20) serotypes as detected from culture or UAD were reported. RESULTS: Six studies (n = 2, United States; n = 1 each, Germany, Sweden, Spain, and Greece) were included. The percentage of RAD + CAP among adults ≥18 years with PCV13 serotypes equaled 4.6% to 12.9%, with PCV15 serotypes 5.9% to 14.5%, and with PCV20 serotypes 7.8% to 23.8%. The percentage of RAD + CAP due to PCV15 and PCV20 serotypes was 1.1-1.3 and 1.3-1.8 times higher than PCV13 serotypes, respectively. CONCLUSIONS: PCV13 serotypes remain a cause of RAD + CAP among adults even in settings with pediatric PCV use. Higher valency PCVs among adults could address an important proportion of RAD + CAP in this population.

Trastuzumab deruxtecan in patients with metastatic non-small-cell lung cancer (DESTINY-Lung01): primary results of the HER2-overexpressing cohorts from a single-arm, phase 2 trial.

BACKGROUND: DESTINY-Lung01 is a multicentre, open-label, phase 2 study evaluating the antitumour activity and safety of trastuzumab deruxtecan, a HER2-directed antibody-drug conjugate, in patients with HER2-overexpressing or HER2 (ERBB2)-mutant unresectable or metastatic non-small-cell lung cancer (NSCLC). The results of the HER2-mutant cohort (cohort 2) have been reported elsewhere. Herein, we report the primary analysis of cohorts 1 and 1A, which aimed to evaluate the activity and safety of trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg in patients with HER2-overexpressing NSCLC. METHODS: Patients aged 18 years or older with unresectable or metastatic (or both unresectable and metastatic) non-squamous NSCLC who had relapsed following or were refractory to standard treatment or for whom no standard treatment was available, with an HER2 immunohistochemistry score of 3+ or 2+ (without known HER2 mutations) and an Eastern Cooperative Oncology Group performance status score of 0 or 1, were enrolled at 20 specialist hospitals in France, Japan, the Netherlands, Spain, and the USA. Patients were assigned to cohorts sequentially, first to cohort 1, to receive trastuzumab deruxtecan 6·4 mg/kg (cohort 1), then to cohort 1A, to receive trastuzumab deruxtecan 5·4 mg/kg, both administered intravenously once every 3 weeks. The primary endpoint was confirmed objective response rate by independent central review and was assessed in the full analysis set, which included all patients who signed an informed consent form and were enrolled in the study. Safety was assessed in all enrolled patients who received at least one dose of trastuzumab deruxtecan. This trial is registered with ClinicalTrials.gov, NCT03505710, and is ongoing (closed to recruitment). FINDINGS: Between Aug 27, 2018, and Jan 28, 2020, 49 patients were enrolled in cohort 1 (median age 63·0 years [IQR 58·0-68·0], 30 [61%] male, 19 [39%] female, and 31 [63%] White), and from June 16 to Dec 9, 2020, 41 patients were enrolled in cohort 1A (median age 62·0 years [IQR 56·0-66·0], 22 [54%] male, 19 [46%] female, and 31 [76%] White). As of data cutoff (Dec 3, 2021), the median treatment duration was 4·1 months (IQR 1·4-7·1) in cohort 1 and 5·5 months (1·4-8·7) in cohort 1A, and median follow-up was 12·0 months (5·4-22·4) in cohort 1 and 10·6 months (4·5-13·5) in cohort 1A. Confirmed objective response rate by independent central review was 26·5% (95% CI 15·0-41·1; 13 of 49, all partial responses) in cohort 1 and 34·1% (20·1-50·6; 14 of 41; two complete responses and 12 partial responses) in cohort 1A. The most common treatment-emergent adverse events of grade 3 or worse were neutropenia (12 [24%] of 49 in cohort 1, none in cohort 1A), pneumonia (six [12%] and two [5%], respectively), fatigue (six [12%] and three [7%], respectively), and disease progression (six [12%] and four [10%], respectively). Drug-related treatment-emergent adverse events of grade 3 or worse occurred in 26 (53%) of 41 patients in cohort 1 and nine (22%) of 49 patients in cohort 1A. Drug-related serious adverse events were reported in ten (20%) patients and three (7%) patients, respectively. Deaths due to treatment-emergent adverse events occurred in ten (20%) patients in cohort 1 (disease progression in six (12%) patients and bronchospasm, hydrocephalus, respiratory failure, and pneumonitis in one [2%] patient each), and in seven (17%) patients in cohort 1A (due to disease progression in four (10%) patients and dyspnoea, malignant neoplasm, and sepsis in one (2%) patient each). One death due to a treatment-emergent adverse event was determined to be due to study treatment by the investigator, which was in cohort 1 (pneumonitis). Independent adjudication of interstitial lung disease or pneumonitis found that drug-related interstitial lung disease or pneumonitis occurred in ten (20%) patients in cohort 1 (two [4%] grade 1, five [10%] grade 2, and three [6%] grade 5) and two (5%) patients in cohort 1A (one [2%] grade 2 and one [2%] grade 5). An additional patient in cohort 1A had grade 4 pneumonitis after the data cutoff, which was subsequently adjudicated as drug-related grade 5 interstitial lung disease or pneumonitis. INTERPRETATION: Given the low antitumour activity of existing treatment options in this patient population, trastuzumab deruxtecan might have the potential to fill a large unmet need in HER2-overexpressing NSCLC. Our findings support further investigation of trastuzumab deruxtecan in patients with HER2-overexpressing NSCLC. FUNDING: Daiichi Sankyo and AstraZeneca.

Bidirectional mode-locked erbium-doped fiber laser based on an all-fiber gold nanofilm saturable absorber.

We demonstrate a bidirectional mode-locked erbium-doped fiber laser by incorporating gold nanofilm as a saturable absorber (SA). The gold nanofilm SA has the advantages of high stability and high optical damage threshold. Besides, the SA exhibits a large modulation depth of 26% and a low saturation intensity of 1.22 MW/cm2 at 1.56 µm wavelength band, facilitating the mode-locking of bidirectional propagating solitons within a single laser cavity. Bidirectional mode-locked solitons are achieved, with the clockwise pulse centered at 1568.35 nm and the counter-clockwise one at 1568.6 nm, resulting in a slight repetition rate difference of 19 Hz. Moreover, numerical simulations are performed to reveal the counter-propagating dynamics of the two solitons, showing good agreement with the experimental results. The asymmetric cavity configuration gives rise to distinct buildup and evolution dynamics of the two counter-propagating pulses. These findings highlight the advantage of the gold nanofilm SA in constructing bidirectional mode-locked fiber lasers and provide insights for understanding the bidirectional pulse propagation dynamics.

Outcomes of one-stage and two-stage aneurysm repair in arteriovenous fistulae.

OBJECTIVE: Maintenance of long-term arteriovenous access is important in long-term care for patients with end-stage renal disease. Arteriovenous access is associated in the long term with the development of fistula aneurysms (FAs). This study aims to evaluate the outcomes of staged FA treatment in dialysis access arteriovenous fistulae (AVF). METHODS: A retrospective review of all patients over a 12-year period with primary autogenous AVF was undertaken at a single center. Patients undergoing elective open aneurysm repair were identified and were categorized into three groups: single FA repair (single, control group) and staged and unstaged repair of two FAs (staged and unstaged). A staged repair was a procedure in which the initial intent was to treat both aneurysms in the AVF and in which the most symptomatic aneurysm was treated first. When the incision from the first surgery had healed, the second symptomatic aneurysm in the AVF was treated. An unstaged repair was a procedure in which the initial intent was to repair both symptomatic aneurysms simultaneously. All patients had a fistulogram before the FA repair. Thirty-day outcomes, cannulation failure, line placement, reintervention, and functional dialysis (continuous hemodialysis for 3 consecutive months) were examined. RESULTS: Five hundred twenty-seven patients presented with FA that met requirements for open intervention; 44% underwent single FA repair, whereas the remaining 34% and 22% underwent staged and unstaged repair of two FAs, respectively. The majority of patients were diabetic and Hispanic. Ninety-one percent of the patients required percutaneous interventions of the outflow tract (37%) and the central veins (54%). Thirty-day major adverse cardiovascular events were equivalent across all modalities. Thirty-day morbidity and early thrombosis (<18 days) were significantly higher in the unstaged group (4.3%) compared with the two other groups (1.3% and 2.1%, single and staged, respectively), which led to an increased need for a short-term tunneled catheter (8.9%) compared with the two other groups (3.4% and 4.4%, single and staged, respectively), Unstaged repair resulted in an increased incidence of secondary procedures (5.0%) compared with the two other groups (2.6% and 3.1%, single and staged, respectively). Functional dialysis at 5 years was equivalent in the single and staged groups but was significantly decreased in the unstaged group. CONCLUSIONS: Open interventions are successful therapeutic modalities for FAs, but unstaged rather than staged repair of two concurrent FAs results in a higher early thrombosis, an increased secondary intervention rate, and a need for a short-term tunneled central line. Staged and single FA repairs have equivalent results. In the setting of two symptomatic FAs, staged repair is recommended.

Long non-coding RNA Linc00657 up-regulates Skp2 to promote the progression of cervical cancer through lipid reprogramming and regulation of immune microenvironment.

More and more evidence shows that long non-coding RNA (lncRNA) plays an important role in the biological behavior of many kinds of malignant tumors, but the specific function of lncRNA Linc00657 in cervical cancer is still unknown. The purpose of this study is to explore the effect of Linc00657 on the malignant progression of cervical cancer and its potential mechanism. In two kinds of cervical cancer cell lines and normal cervical epithelial cells, qRT-PCR showed increased expression of Linc00657 in cervical cancer cells. Through MTT, clone formation test, flow cytometry, wound healing test and Transwell test, it has been found that overexpression of Linc00657 could promote the proliferation,migration and invasion of cervical cancer cells，and inhibit apoptosis. Through the StarBase database, it was found that there may be a mutual regulatory relationship between Linc00657 and Skp2, and Skp2 may be the downstream target of Linc00657. QRT-PCR detection confirmed that the expression of Skp2 was increased in cervical cancer cells with overexpression of Linc00657. TIMER2 database found that Skp2 was associated with lipid metabolic enzymes and immune cell infiltration. It was found that Linc00657 knockdown inhibited tumor growth and metastasis and inhibited the expression of Skp2 in vivo. In short, our research shows that Linc00657 has carcinogenic properties in cervical cancer, and LINC00657 promotes the occurrence of cervical cancer by up-regulating the expression of Skp2. We predict that Linc00657/mir30s/Skp2 axis plays a role in the malignant progression of cervical cancer. In addition, Skp2 may participate in cancer immune response and promote lymph node metastasis of cervical cancer through lipid reprogramming. These findings also provide promising targets for the diagnosis and treatment of cervical cancer.

Gut microbiome in diabetic retinopathy: A systematic review and meta-analysis.

CONTEXT: Changes in the gut microbiome are linked with Type 2diabetes mellitus (T2DM) development, but alterations in patients with diabetic retinopathy (DR) are still being debated. OBJECTIVE: To investigate the differences in biodiversity and relative abundance of gut microbiome between patients with DR and T2DM. METHODS: A comprehensive search was performed in five electronic databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, and CNKI) from the inception of each database through to August 2023. The standardized mean difference (SMD) and its 95% confidence interval (CI) were estimated using Stata 15.1. Furthermore, the alpha diversity index and relative abundance of the gut microbiome were calculated. The Egger test determined publication bias in the literature. RESULTS: Seven case-control studies were included in the final dataset, comprising 195 patients with DR and 211 patients with T2DM. Compared to T2DM patients, patients in the DR group had a reduced but not significantly different α-diversity. The analysis of microbial composition at the phylum level revealed a marked increase in the relative abundance of Bacteroidetes(ES = 23.27, 95%CI[8.30, 38.23], P = 0.000) and a decline in Firmicutes(ES = 47.05, 95%CI[36.58, 57.52], P = 0.000), Proteobacteria (ES = 11.08, 95%CI[6.08, 16.07], P = 0.000) and Actinobacteria (ES = 10.43, 95%CI[1.64, 19.22], P = 0.001) in patients with DR when compared to those with T2DM. CONCLUSIONS: An association exists between alterations in the gut microbiome of T2DM and the development and progression of DR. This suggests that re-establishing homeostasis of the gut microbiome could be a potential way to prevent or treat DR and requires further confirmation in future studies. REGISTRATION DATABASE: Prospero. REGISTRATION NUMBER: CRD42023455280.

Customized Synthesis of MOF Nanoplates via Molecular Scalpel Strategy for Efficient Oxygen Reduction in Zn-Air Batteries.

The production of metal-organic framework (MOF) nanoplates with well-defined geometric morphology is remarkable for expanding their applications. Herein, the cobalt-based MOF nanoplates with hexagonal channels from a layer-pillared MOF are accomplished, via a molecular scalpel strategy, utilizing monodentate pyridine to replace the bidentate 4,4'-bipyridine. The morphology can be modified from nanorods to nanoplates with controllable thickness tuned by the amounts of pyridine. Succeeding carbonization treatment transforms the MOF nanoplates into Co particles homogeneously encapsulated in the nitrogen-doped carbon layers. The prepared catalyst with a unique platelike morphology displays a high half-wave potential of 0.88 V in oxygen reduction reaction. When used in primary Zn-air batteries, it delivers a high peak power density of 280 mW cm-2 . This work clarifies the structure-morphology-reactivity connection of MOF nanoplates.

A regional genomic surveillance program is implemented to monitor the occurrence and emergence of SARS-CoV-2 variants in Yubei District, China.

BACKGROUND: In December 2022, Chongqing experienced a significant surge in coronavirus disease 2019 (COVID-19) epidemic after adjusting control measures in China. Given the widespread immunization of the population with the BA.5 variant, it is crucial to actively monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant evolution in Chongqing's Yubei district. METHODS: In this retrospective study based on whole genome sequencing, we collected oropharyngeal and nasal swab of native COVID-19 cases from Yubei district between January to May 2023, along with imported cases from January 2022 to January 2023. Through second-generation sequencing, we generated a total of 578 genomes. RESULTS: Phylogenetic analyses revealed these genomes belong to 47 SARS-CoV-2 Pango lineages. BA.5.2.48 was dominant from January to April 2023, rapidly replaced by XBB* variants from April to May 2023. Bayesian Skyline Plot reconstructions indicated a higher evolutionary rate (6.973 × 10-4 subs/site/year) for the XBB.1.5* lineage compared to others. The mean time to the most recent common ancestor (tMRCA) of BA.5.2.48* closely matched BA.2.75* (May 27, 2022). Using multinomial logistic regression, we estimated growth advantages, with XBB.1.9.1 showing the highest growth advantage (1.2, 95% HPI:1.1-1.2), followed by lineage FR.1 (1.1, 95% HPI:1.1-1.2). CONCLUSIONS: Our monitoring reveals the rapid replacement of the previously prevalent BA.5.2.48 variant by XBB and its sub-variants, underscoring the ineffectiveness of herd immunity and breakthrough BA.5 infections against XBB variants. Given the ongoing evolutionary pressure, sustaining a SARS-CoV-2 genomic surveillance program is imperative.

Preparation and Reactivity of Core-Shell Al@CL-20 Composites Embedded with Graphene-Based Complexes as Catalysts.

Incomplete combustion of Al in solid propellants can be effectively resolved by coating of an oxidizer at the microscale. In this paper, Al@CL-20 composites with polydopamine as the interfacial layer were prepared using this strategy. The structure, heat of reaction, thermal decomposition properties, and combustion performances of these composites under the effects of graphene oxide (GO) and graphene-based carbohydrazide complexes (GO-CHZ-M, M = Co2+, Ni2+) have been comprehensively investigated. The experimental results show that the heat of reaction of Al@CL-20 is 6482 J g-1, which is 561 J g-1 higher than that of the corresponding mechanical mixture. The presence of GO-CHZ-Co can further increase the heat of reaction of Al@CL-20 to 6729 J g-1 with a decreased activation energy by about 54.8%. Under the synergistic effect of interfacial control and GO-CHZ-M, the ignition delay time of Al@CL-20-Co decreases from 5.1 to 4.2 ms. Besides, the D50 of the combustion condensed products (CCPs) decreased from 5.62 to 4.33 µm, indicating the combustion efficiency of Al is greatly improved.

Amniocentesis in pregnancies at or beyond 24 weeks: An international multicenter study.

BACKGROUND: Amniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation, but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale, multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse. OBJECTIVES: To evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation. STUDY DESIGN: We conducted an international, multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved nine referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and post-procedure complications. RESULTS: Of the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within two weeks post-procedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24-28 weeks and those between 28-32 weeks, reinforcing the procedure's safety across these gestational periods. CONCLUSIONS: Late amniocentesis, at or after 24 weeks gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.

Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines.

The copper-catalyzed enantioselective allylation reaction of N-aryl aldimines has been developed using a combination of Cu(OAc)2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho-substituents on the N-aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N-aryl motif, three kinds of N-heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.

Structurally diverse stilbenes from Gnetum parvifolium and their anti-neuroinflammatory activities.

Phytochemical investigation on the aerial parts of Gnetum parvifolium led to the isolation of 15 new and eight known structurally diverse stilbenes. The isolated compounds comprised (E)- or (Z)-stilbene (1-6, 15-20), dihydrostilbene (21), phenylbenzofuran (7, 8, 22), benzylated stilbene (9-11), benzylated stilbene dimer (12), and nitrogen-containing stilbene (13a, 13b, 14) types. The structures of the new compounds (1-12, 13a, 13b, 14) were established through spectroscopic analyses and experimental and calculated ECD data. Compound 12 is the first stilbene dimer connected through a benzyl group. In the anti-neuroinflammatory activity assay, compounds 4, 5, 9-11, 13b, and 16-21 displayed significant inhibitory effects against LPS-induced NO release in BV-2 microglial cells, with IC50 values of 0.35-16.1 µM. Compound 10 had the most potent activity (IC50 = 0.35 µM), and the further research indicated that it could decrease the mRNA levels of iNOS, IL-1ß, IL-6, and TNF-α in a dose-dependent manner.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.

Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m6 modification.

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease. By using a custom-designed smoke-exposure mouse system, we demonstrated that CS results in intervertebral disc (IVD) degeneration and release of MC-restricted tetramer tryptases (TTs) in the IVDs. TTs were found to regulate the expression of methyltransferase 14 (METTL14) at the epigenetic level by inducing N6-methyladenosine (m6A) deposition in the 3' untranslated region (UTR) of the transcript that encodes dishevelled-axin (DIX) domain-containing 1 (DIXDC1). That reaction increases the mRNA stability and expression of Dixdc1. DIXDC1 functionally interacts with disrupted in schizophrenia 1 (DISC1) to accelerate the degeneration and senescence of nucleus pulposus (NP) cells by activating a canonical Wnt pathway. Our study demonstrates the association between CS, MC-derived TTs, and LBP. These findings raise the possibility that METTL14-medicated DIXDC1 m6A modification could serve as a potential therapeutic target to block the development of degeneration of the NP in LBP patients.

Effect of implant shape and length on the accuracy of robot-assisted immediate implant surgery: An in vitro study.

OBJECTIVES: To compare the accuracy of immediate implant placement of cylindrical implants (CI) and tapered implants (TI) of different lengths using a robotic dental implant system. MATERIALS AND METHODS: CI and TI of three lengths (8, 10, and 12 mm) each were digitally planned and placed in a three-dimensional printed extraction socket model under robotic guidance. There were six groups with three samples in each group, resulting in a total of 18 samples. Implant angular deviation, platform point deviation (total, lateral, depth), and implant apical point deviation (total, lateral, depth) were recorded and compared between the different groups. RESULTS: The angular deviations for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 1.32° ± 0.19°, 1.03° ± 0.56°, 1.31° ± 0.38°, 1.27° ± 0.64°, 1.10° ± 0.43° and 1.05° ± 0.45°, respectively. The total deviations of platform and apical points for CI 8 mm, CI 10 mm, CI 12 mm, TI 8 mm, TI 10 mm, and TI 12 mm were 0.79 ± 0.18 mm, 0.77 ± 0.33 mm; 0.64 ± 0.21 mm, 0.55 ± 0.17 mm; 0.64 ± 0.37 mm, 0.65 ± 0.34 mm; 0.68 ± 0.26 mm, 0.71 ± 0.20 mm; 0.70 ± 0.12 mm, 0.66 ± 0.23 mm; and 0.71 ± 0.15 mm, 0.77 ± 0.29 mm, respectively, and had no significant differences. CONCLUSIONS: Within the limitation of this study, acceptable accuracy can be achieved for both TI and CI using robotic systems. Our study demonstrated that the implant shape and length did not affect the accuracy of immediate implant placement under robotic guidance in vitro. However, further trials are required to confirm their efficacy in clinical practice.