Search

Objective To explore the efficacy and safety of intracranial-intracranial bypass for the treatment of complex intracranial aneurysms. Methods and Results A total of 32 patients with complex intracranial aneurysms who were hospitalized for treatment at Huashan Hospital, Fudan University from January 2015 to December 2023 were included. Surgical methods included in-situ bypass, reimplantation, reanastomosis and bypass with interposition graft. For middle cerebral artery (MCA) aneurysms (n = 16), there were 5 cases of in-situ bypass, one case of reimplantation, 3 cases of reanastomosis, and 7 cases of bypass with interposition graft. For anterior cerebral artery (ACA) aneurysms (n = 8), there were 5 cases of in-situ bypass and 3 cases of reimplantation. For anterior communicating artery (ACoA) aneurysms (n = 2), both cases were in-situ bypass. For posterior circulation aneurysms (n = 6), there were 3 cases of in-situ bypass, 2 cases of reanastomosis, and one case of bypass with interposition graft. The intraoperative graft vessels patency rate was 100%. Among the 23 patients who participated in follow-up imaging for more than 6 months postoperatively, no obvious recurrence was indicated by imaging. Among the 28 patients who participated in modified Rankin Scale (mRS) follow-up, there was one case of 5, 5 cases of 3, 2 cases of 2, one case of 1, and 19 cases of 0. Postoperative hemorrhagic complications occurred in 3 cases (9.37%), and ischemic complications occurred in 10 cases (31.25%), with no patients requiring unplanned secondary surgery for complication treatment. Conclusions Intracranial-intracranial bypass has good efficacy and safety for the treatment of complex intracranial aneurysms and has unique advantages in the microsurgical treatment of complex intracranial aneurysms.

Abstract Background Copy number variations (CNVs) have emerged as significant contributors to the elusive genetic causality of inherited eye diseases. In this study, we describe a case with optic atrophy and a brain aneurysm, in which a de novo CNV 3q29 deletion was identified. Case presentation A 40-year-old female patient was referred to our department after undergoing aneurysm transcatheter arterial embolization for a brain aneurysm. She had no history of systemic diseases, except for unsatisfactory best-corrected visual acuity (BCVA) since elementary school. Electrophysiological tests confirmed the findings in retinal images, indicating optic nerve atrophy. Chromosomal microarray analysis revealed a de novo deletion spanning 960 kb on chromosome 3q29, encompassing OPA1 and six neighboring genes. Unlike previously reported deletions in this region associated with optic atrophy, neuropsychiatric disorders, and obesity, this patient displayed a unique combination of optic atrophy and a brain aneurysm. However, there is no causal relationship between the brain aneurysm and the CNV. Conclusion In conclusion, the optic atrophy is conclusively attributed to the OPA1 deletion, and the aneurysm could be a coincidental association. The report emphasizes the likelihood of underestimating OPA1 deletions due to sequencing technology limitations. Recognizing these constraints, healthcare professionals must acknowledge these limitations and consistently search for OPA1 variants/deletions in Autosomal Dominant Optic Atrophy (ADOA) patients with negative sequencing results. This strategic approach ensures a more comprehensive exploration of copy-number variations, ultimately enhancing diagnostic precision in the field of genetic disorders.

Abstract The synthesis of dynamic chiral lanthanide complex emitters has always been difficult. Herein, we report three pairs of dynamic chiral EuIII complex emitters (R/S -Eu-R-1, R = Et/Me; R/S -Eu-Et-2) with aggregation-induced emission. In the molecular state, these EuIII complexes have almost no obvious emission, while in the aggregate state, they greatly enhance the EuIII emission through restriction of intramolecular rotation and restriction of intramolecular vibration. The asymmetry factor and the circularly polarized luminescence brightness are as high as 0.64 (5 D 0 → 7 F 1) and 2429 M−1cm−1 of R -Eu-Et-1, achieving a rare double improvement. R -Eu-Et-1/2 exhibit excellent sensing properties for low concentrations of CuII ions, and their detection limits are as low as 2.55 and 4.44 nM, respectively. Dynamic EuIII complexes are constructed by using chiral ligands with rotor structures or vibration units, an approach that opens a door for the construction of dynamic chiral luminescent materials.

Highlights Critical solvation structure changes the hydrogen bond network through “catchers”. Catcher further arrests the active molecules to promote Zn2+ deposition. The Zn||Zn symmetric battery can stably cycle for 2250 h. Zn||V6O13 full battery achieved a capacity retention rate of 99.2% after 10,000 cycles.

[Objective] Water and land resources are important factors of production for urban development. It is of great significance to explore the key factors in the utilization of water and soil resources in urban agglomerations in the middle reaches of the Yellow River to scientifically promote the rapid economic development of urban agglomerations in the middle reaches of the Yellow River. [Methods] Taking the three major urban agglomerations in the middle reaches of the Yellow River as an example, by using LMDI addition model, the decomposition models of factors affecting the change of water resources consumption and the change of urban construction land quantity were constructed respectively for the three major urban agglomerations in the middle reaches of the Yellow River from 2010 to 2019, and the effect values of different driving factors were calculated and compared. [Results] (1) Water use quota and industrial structure can inhibit the increase of water resource consumption, while economic scale and population scale will promote its increase. (2) The industrial scale, economic scale and population scale have a driving effect on the expansion of construction land, while the consumption intensity of urban construction land has a restraining effect on the expansion of construction land. (3) For the change of water resources utilization, there is a large gap in the optimization level of industrial structure among different cities in the middle reaches of the Yellow River; for the change of urban construction land, the comparison result of the total effect value of the three major urban agglomerations is Guanzhong Plain urban agglomeration > Central Plains urban agglomeration > Jinzhong urban agglomeration. [Conclusion] Discussing the factors affecting the utilization of water and land resources in urban agglomerations in the middle reaches of the Yellow River from the perspective of regional differences and time differences will help to enrich relevant research on the sustainable use of water and land resources, and provide theoretical guidance for the sustainable development of urban agglomerations in the middle reaches of the Yellow River.

Abstract Background Sparganosis is a worldwide food-borne parasitic disease caused by spargana infection, which infects the muscle of frogs and snakes as well as many tissues and organs in humans. There are currently no viable treatments for sparganosis. Understanding spargana’s nutrition source and carbohydrate metabolism may be crucial for identifying its energy supply and establishing methods of treatment for sparganosis. Methods Using an amino acid analyzer and nutrient concentration detection kits, we assessed nutrient concentrations in the muscles of Fejervarya limnocharis and Pelophylax plancyi infected or not infected with spargana. Quantitative polymerase chain reaction (PCR) was used to quantify the major enzymes involved in five glucose metabolism pathways of spargana developing in vivo. We also used quantitative PCR to assess key enzymes and transcriptome sequencing to explore the regulation of carbohydrate metabolic pathways in vitro in response to different 24-h food treatments. Results Infected muscle tissues had considerably higher concentrations of glucogenic and/or ketogenic amino acids, glucose, and glycogen than non-infected muscle tissues. We discovered that the number of differentially expressed genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was larger in low-glucose than in other dietary groups. We examined differences in the expression of genes producing amino acid transporters, glucose transporters, and cathepsins in spargana grown in various nutritional environments. In the normal saline group, only the major enzymes in the tricarboxylic acid cycle (TCA), glycogenesis, and glycogenolysis pathways were expressed. The l-glutamine group had the greatest transcriptional levels of critical rate-limiting enzymes of gluconeogenesis and glycogenesis. Furthermore, the low-glucose group had the highest transcriptional levels of critical rate-limiting enzymes involved in the TCA, glycolytic, and glycogenolysis pathways. Surprisingly, when compared to the in vitro culturing groups, spargana developing in vivo exhibited higher expression of these critical rate-limiting enzymes in these pathways, with the exception of the pentose phosphate pathway. Conclusions Spargana have a variety of nutritional sources, and there is a close relationship between nutrients and the carbohydrate metabolism pathways. It takes a multi-site approach to block nutrient absorption and carbohydrate metabolism pathways to provide energy to kill them. Graphical Abstract

Abstract Raman spectroscopy has tremendous potential for material analysis with its molecular fingerprinting capability in many branches of science and technology. It is also an emerging omics technique for metabolic profiling to shape precision medicine. However, precisely attributing vibration peaks coupled with specific environmental, instrumental, and specimen noise is problematic. Intelligent Raman spectral preprocessing to remove statistical bias noise and sample-related errors should provide a powerful tool for valuable information extraction. Here, we propose a novel Raman spectral preprocessing scheme based on self-supervised learning (RSPSSL) with high capacity and spectral fidelity. It can preprocess arbitrary Raman spectra without further training at a speed of ~1 900 spectra per second without human interference. The experimental data preprocessing trial demonstrated its excellent capacity and signal fidelity with an 88% reduction in root mean square error and a 60% reduction in infinite norm ( $${L}_{{\infty }}$$ L ∞ ) compared to established techniques. With this advantage, it remarkably enhanced various biomedical applications with a 400% accuracy elevation (ΔAUC) in cancer diagnosis, an average 38% (few-shot) and 242% accuracy improvement in paraquat concentration prediction, and unsealed the chemical resolution of biomedical hyperspectral images, especially in the spectral fingerprint region. It precisely preprocessed various Raman spectra from different spectroscopy devices, laboratories, and diverse applications. This scheme will enable biomedical mechanism screening with the label-free volumetric molecular imaging tool on organism and disease metabolomics profiling with a scenario of high throughput, cross-device, various analyte complexity, and diverse applications.

Purpose: Cone-rod dystrophies (CORD) are inherited retinal dystrophies characterized by primary cone degeneration with secondary rod involvement. We report two patients from the same family with a dominant variant in the guanylate cyclase 2D (GUCY2D) gene with different phenotypes in the electroretinogram (ERG). Observations: A 21-year-old lady (Patient 1) was referred due to experiencing blurry vision and color vision impairment. Visual field testing revealed a central scotoma. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) documented macula dysfunction. Reduced amplitude was observed in the photopic responses of ERG. Her 54-year-old father (Patient 2) had similar issues with blurry vision. A dilated fundus examination displayed bilateral macular atrophy. Loss of the ellipsoid zone line and collapse of the outer nuclear segment were noted on the SD-OCT. Photopic ERG responses were extinguished, and an electronegative ERG was observed in the dark-adapted 3.0 ERG. The gene report revealed a c.2512C > T (p.Arg838Cys) variant in GUCY2D for both patients. They were respectively diagnosed as cone dystrophy (COD) and cone-rod dystrophy (CORD). Conclusions: We report two different clinical phenotypes in GUCY2D-associated COD despite sharing the same variant. A dysfunction in the synaptic junction between the photoreceptor and the secondary neuron was proposed to explain the electronegative ERG. This explanation might extend to other gene-related cases of CORD with electronegative ERG.

Based on a previously reported 1,4-dihydropyridinebutyrolactone virtual screening hit, nine lactone ring-opened ester and seven amide analogs were prepared. The analogs were designed to provide interactions with residues at the entrance of the ZA loop of the testis-specific bromodomain (ZA) channel to enhance the affinity and selectivity for the bromodomain and extra-terminal (BET) subfamily of bromodomains. Compound testing by AlphaScreen showed that neither the affinity nor the selectivity of the ester and lactam analogs was improved for BRD4-1 and the first bromodomain of the testis-specific bromodomain (BRDT-1). The esters retained affinity comparable to the parent compound, whereas the affinity for the amide analogs was reduced 10-fold. A representative benzyl ester analog was found to retain high selectivity for BET bromodomains as shown by a BROMOscan. X-ray analysis of the allyl ester analog in complex with BRD4-1 and BRDT-1 revealed that the ester side chain is located next to the ZA loop and solvent exposed.

IntroductionNicotinamide adenine dinucleotide (NAD) is a crucial molecule in cellular metabolism and signaling. Mapping intracellular NAD content of human brain has long been of interest. However, the sub-millimolar level of cerebral NAD concentration poses significant challenges for in vivo measurement and imaging.MethodsIn this study, we demonstrated the feasibility of non-invasively mapping NAD contents in entire human brain by employing a phosphorus-31 magnetic resonance spectroscopic imaging (31P-MRSI)-based NAD assay at ultrahigh field (7 Tesla), in combination with a probabilistic subspace-based processing method.ResultsThe processing method achieved about a 10-fold reduction in noise over raw measurements, resulting in remarkably reduced estimation errors of NAD. Quantified NAD levels, observed at approximately 0.4 mM, exhibited good reproducibility within repeated scans on the same subject and good consistency across subjects in group data (2.3 cc nominal resolution). One set of higher-resolution data (1.0 cc nominal resolution) unveiled potential for assessing tissue metabolic heterogeneity, showing similar NAD distributions in white and gray matter. Preliminary analysis of age dependence suggested that the NAD level decreases with age.DiscussionThese results illustrate favorable outcomes of our first attempt to use ultrahigh field 31P-MRSI and advanced processing techniques to generate a whole-brain map of low-concentration intracellular NAD content in the human brain.

Hedysarum qilianshanense sp. nov. (Fabaceae, Hedysareae) is described and illustrated from the Qilianshan Mountains in Gansu, China. This new species is similar to H. przewalskii, but can be distinguished by its corolla being light purple to purple, standard 15–19 mm long, wings 14–16 mm long, keels 16–19 mm long, and the ovary and legume being glabrous. The new species can be easily distinguished from H. neglectum Ledeb. by its bract being shorter than the pedicel, and the ovary and legume being glabrous. Phylogenetic tree based on the nuclear ITS and ETS sequences shows that H. qilianshanense is sister to H. przewalskii, while the tree based on the plastid psbA-trnH, trnC-petN, trnL-F, trnS-G and petN-psbM sequences shows H. qilianshanense as sister to a clade consisting of H. hedysaroides, H. inundatum, H. americanum and H. neglectum. The new species is a diploid with the chromosome number 2n = 14. Based on morphological, phylogenetic and karyotypic evidence, the new species may originate from an ancient homoploid hybrid speciation event.

Abstract Background The elderly with severe infection increased dramatically in intensive care unit (ICU). Proper antimicrobial therapy help improve the prognosis. Linezolid, as an antimicrobial drug, is commonly utilized to treat patients infected with methicillin-resistant S. aureus and vancomycin-resistant enterococci. Clinical evidence suggests elderly patients prone to linezolid overexposure. Here, we describe the results of three years’ linezolid adjustment experiences according to therapeutic drug monitoring (TDM), especially in the oldest old. Methods Linezolid therapeutic drug monitoring data were collected between January 2020 and November 2022 from patients who were admitted to ICU and treated with linezolid. All the patients started with a dosage of 600 mg, twice daily. The first TMD was carried out ten minutes before the seventh administration. The dosage adjustment was determined by the doctor according to the first TMD and patients' condition, and the repeated TDM was conducted as required. The dosage adjustment in different age group was recorded. Laboratory data were compared between the old and the oldest old. The high mortality risk of the oldest old was also explored. Results Data of 556 linezolid TDM from 330 patients were collected. Among which, 31.6%, 54.8%, and 75% of patients had supra-therapeutic linezolid trough concentrations at the first TDM assessment in different age group, leading to the dosage adjustment rate of 31.0%, 40.3%, 68.8% respectively. The linezolid dosage adjustments according to TDM help to reach therapeutic concentration. The oldest old was in high risk of linezolid overexposure with lowercreatinine clearance. The norepinephrine maximum dosage but not linezolid Cmin was associated with 28-day mortality in the oldest old. Conclusions Elderly patients with linezolid conventional 600 mg twice-daily dose might be at a high risk of overexposure, especially in the oldest old. The linezolid dosage adjustments according to TDM help reach the therapeutic concentration. The high mortality of the oldest old was not related with initial linezolid overexposure.

Ambient air pollution is a major global health concern. Yet, no study has thoroughly assessed its link to respiratory mortality. Our research evaluated the combined and individual effects of air pollutants on respiratory mortality risks based on the UK Biobank. A total of 366,478 participants were studied. A Cox proportional hazards model was used to estimate the respiratory mortality risk from combined long-term exposure to five pollutants, summarized as a weighted air pollution score. During a median of 13.6 years of follow-up, 6113 deaths due to respiratory diseases were recorded. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) of respiratory diseases were 2.64 (2.05–3.39), 1.62 (1.23–2.12), 2.06 (1.73–2.45), 1.20 (1.16–1.25), and 1.07 (1.05–1.08) per 10 μg/m3 increase in PM2.5, PM2.5–10, PM10, NO2, and NOx, respectively. The air pollution score showed a dose-response association with an elevated respiratory mortality risk. The highest versus lowest quartile air pollution score was linked to a 44% increase in respiratory mortality risk (HR 1.44, 95% CI: 1.33–1.57), with consistent findings in subgroup and sensitivity analyses. Long-term individual and joint air-pollutant exposure showed a dose-response association with an increased respiratory mortality risk, highlighting the importance of a comprehensive air-pollutant assessment to protect public health.

Abstract To describe the pharmacokinetics/pharmacodynamics (PK/PD) of a 2 h infusion of ceftazidime‐avibactam (CAZ‐AVI) in critically ill patients with augmented renal clearance (ARC). A retrospective review of all critically ill patients with ARC who were treated with CAZ‐AVI between August 2020 and May 2023 was conducted. Patients whose 12‐h creatinine clearance prior to CAZ‐AVI treatment and steady‐state concentration (Css) of CAZ‐AVI were both monitored were enrolled. The free fraction (fCss) of CAZ‐AVI was calculated from Css. The joint PK/PD targets of CAZ‐AVI were considered optimal when a Css/minimum inhibitory concentration (MIC) ratio for CAZ ≥4 (equivalent to 100% fT > 4 MIC) and a Css/CT ratio of AVI >1 (equivalent to 100% fT > CT 4.0 mg/L) were reached simultaneously, quasioptimal when only one of the two targets was reached, and suboptimal when neither target was reached. The relationship between PK/PD goal achievement, microbial eradication and the clinical efficacy of CAZ‐AVI was evaluated. Four patients were included. Only one patient achieved optimal joint PK/PD targets, while the other three reached suboptimal targets. The patient with optimal PK/PD targets achieved microbiological eradication, while the other three patients did not, but all four patients achieved good clinical efficacy. Standard dosages may not enable most critically ill patients with ARC to reach the optimal joint PK/PD targets of CAZ‐AVI. Optimal drug dose adjustment of CAZ‐AVI in ARC patients requires dynamic drug concentration monitoring.

Background: Conflicting results have been reported on the association of dietary unsaturated fatty acids (UFAs) with longevity and cardiovascular health. Most previous studies have focused only on the amount of UFAs consumed, not the timing of intake. Methods: This prospective cohort study used data from 30,136 adults aged 18 years and older. Intakes of UFAs by meal time and types were assessed by a 24-h dietary recall for two days. The covariate-adjusted survey-weighted Cox proportional hazards models were performed to evaluate the associations of dietary total unsaturated fatty acid (TUFA), polyunsaturated fatty acid (PUFA), and monounsaturated fatty acid (MUFA) intakes throughout the day and three meals with mortality. Results: During a median of 10.0 years of follow-up, 4510 total deaths occurred. All-cause mortality decreased with increasing intakes at dinner of TUFA (HR: 0.87 [0.77–0.98]), PUFA (HR: 0.81 [0.73–0.91]), and MUFA (HR: 0.88 [0.77–0.99]). With an increased intake of PUFA at dinner, CVD mortality showed a decreasing trend. However, the inverted L-shaped non-linear trend in all-cause mortality was found with increasing intake at breakfast of TUFA (HR: 1.35 [1.17–1.57], Q3 vs. Q1), PUFA (HR: 1.30 [1.13–1.50]), and MUFA (HR: 1.28 [1.13–1.45]). Meanwhile, increased breakfast intake of UFAs was associated with increased CVD and heart disease mortality. Conclusions: Meal timing influences the association of UFAs with all-cause and CVD-related mortality.

Surface-enhanced Raman scattering (SERS) provides an alternative rapid detection method for pesticide residues in food, but fenvalerate possesses poor affinity to the novel metal substrate, thus restricting its analysis. To break this bottleneck, a SERS-active platform with an Ag/rGO composite structure was engineered using a facile method for fenvalerate detection. Ag nanoparticles with a 60 nm diameter can grow evenly on the top and bottom of rGO layers under intense ultrasonic oscillation, and rGO in hybrid material acts as an ideal hotspot holder between the gaps of Ag nanoparticles, not only allowing the interaction area to be enhanced both electromagnetically and chemically but also enabling the capture and enrichment of fenvalerate pesticide molecules into the “hotspot” area to improve detection sensitivity. Ag/rGO composite substrate possesses superior SERS performance with an ultralow detectable concentration of 4-aminothiophenol (10−10 M) and good reproducibility, endowing the material with a better enhancement effect than pure Ag nanoparticles. When used as the SERS substrate for fenvalerate detection, Ag/rGO composite material showed excellent performance in both experiments and theoretical calculation, with the limit of detection (LOD) of fenvalerate being as low as 1.69 × 10−5 mg/kg and a detection model with an R2 of 99.2%, demonstrating its exciting potential as a SERS substrate for pesticides detection.

This paper reports a two-step method for preparing a metal-organic framework (MOF) MIL-101 (Fe) based substrate with high sensitivity and stability for surface-enhanced Raman scattering (SERS) analysis. Firstly, MIL-101 (Fe) nanoparticles were synthesized using a traditional solvothermal method. Next, gold nanoparticles (AuNPs) were produced through a reduction method, and the AuNPs/MIL-101 (Fe) composite substrate was created by combining MIL-101 (Fe) with AuNPs. The adsorption capacity of the substrate and its SERS activity after multiple cleaning were tested. Using Rhodamine 6 G (R6G) as the probe molecule, the substrate's detection capability reached 10-8 M, with a relative standard deviation (RSD) of approximately 13.15%, indicating excellent SERS performance and uniformity. The ideal detection capability for sulfapyridine using the composite matrix can be as low as 10-6 M. This proposed substrate is convenient and efficient, holding great potential for the rapid and sensitive detection of antibiotic residues and other environmental pollutants.