A Highly Conjugated Nickel(II)-Acetylide Framework for Efficient Photocatalytic Carbon Dioxide Reduction.

The incorporation of transition-metal single atoms as molecular functional entities into the skeleton of graphdiyne (GDY) to construct novel two-dimensional (2D) metal-acetylide frameworks, known as metalated graphynes (MGYs), is a promising strategy for developing efficient catalysts, which can combine the tunable charge transfer of GDY frameworks, the catalytic activity of metal and the precise distribution of single metallic centers. Herein, four highly conjugated MGY photocatalysts based on NiII, PdII, PtII, and HgII were synthesized for the first time using the 'bottom-up' strategy through the use of M-C bonds (-C≡C-M-C≡C-). Remarkably, the NiII-based graphyne (TEPY-Ni-GY) exhibited the highest CO generation rate of 18.3 mmol g-1 h-1 and a selectivity of 98.8%. This superior performance is attributed to the synergistic effects of pyrenyl and -C≡C-Ni(PBu3)2-C≡C- moieties. The pyrenyl block functions as an intramolecular π-conjugation channel, facilitating kinetically favorable electron transfer, while the -C≡C-Ni(PBu3)2-C≡C- moiety serves as the catalytic site that enhances CO2 adsorption and activation, thereby suppressing competitive hydrogen evolution. This study provides a new perspective on MGY-based photocatalysts for developing highly active and low-cost catalysts for CO2 reduction.

Investigations of microbial adaptation to singular, binary, and fully formulated quaternary ammonium compounds.

The study was conducted to inform risk assessments concerning microbial exposure to quaternary ammonium biocides (QUATs) by investigating their effects on 10 microbial strains of hygiene relevance. Biocides were divided into three categories: simple aqueous solutions, biocide mixtures, and formulated biocides. Organisms were grown in the presence of biocides for 10 generations and then subsequently for another 10 generations in biocide-free media. Control organisms were passaged 20 times in biocide-free media. Strains were then assessed for biocide and antibiotic susceptibility, changes in growth dynamics, and single nucleotide polymorphisms (SNPs). Biocide mixtures demonstrated greater antimicrobial potency than singular and formulated biocides. Susceptibility changes of under twofold were observed for all biocides tested. Susceptibility decreased significantly for organisms passaged with singular biocides (1.29- to 4.35-fold) and biocide mixtures (1.4- to 1.5-fold), but not for formulated biocides (1.3- to 1.84-fold) compared to controls. Antibiotic susceptibility both increased and decreased in passaged organisms, with heightened susceptibility occurring more frequently in the singular biocide group. Changes in susceptibility and growth dynamics were similar in the passaged and unexposed controls for fitness measures of adapted bacteria; there were no significant differences between biocide groups, but significantly lower generation and doubling times in organisms exposed to singular biocides. Similar frequencies in SNPs occurred for the three biocide groups and unexposed controls. While some adaptations occurred, particularly with singular biocides, the impact on antibiotic resistance and genomic mutations was limited. These findings suggest that the use of formulated QUATs may pose a comparatively lower risk for antimicrobial resistance.IMPORTANCEBiocides are used globally to control microbial growth and effective assessment of the risks and benefits of their use is therefore a high priority. Much of the data used to assess risk has been based on sub-lethal exposure of bacteria to singular biocides in simple aqueous solutions. This work builds on limited prior realism-based studies to demonstrate enhanced potency in biocidal mixtures; the mitigation of resistance selection by formulations and inconsistent cross-resistance effects with both increases and decreases in susceptibility for a wide range of antibiotics. These data can be used to better inform risk assessments of biocide deployment.

Probing the relevance of synergistic lipid membrane disruption to the eye irritation of binary mixed nonionic surfactants.

Nonionic surfactant aerosols play a crucial role in many industries, but they can cause acute irritation to users' eyes during spraying. This cytotoxic process is associated with corneal cell necrosis causing cell membrane disruption. Industrial grade surfactants are typically polydisperse mixtures described by their nominal chemical structure but how the polydispersity affects their interactions with cell membrane, remains largely unexplored. A better understanding could benefit product formulations to maximise their efficiency whilst minimising their toxicity to the users. In this study, poly-oxyethylene glycol monododecyl ethers (C12E4, C12E23) were used to form ideal binary surfactant mixtures. The cytotoxicities of mono and polydispersed surfactants towards human corneal epithelial cells were examined, followed by a series of biophysical characterisations of interactions between surfactants and model cell membranes. Notably, to probe the journey of individual C12E4 and C12E23 surfactant molecules across the cell membrane from a binary surfactant mixture, "two-colour" neutron reflection measurements were achieved via Hydrogen/Deuterium substitution. The relative distributions of C12E4 and C12E23 across cell membranes and their nanostructural conformations revealed a synergistic membrane-lytic ability initiated by surfactant mixing, with the more hydrophobic C12E4 exhibiting stronger membrane binding potency than the hydrophilic C12E23. The exact molar ratio of C12E4 against C12E23 in the mixture determined how the mixed surfactant interacted with the cell membrane, and how the process directly impacted cytotoxicity and eye irritation. Thus, the cytotoxicity of polydisperse surfactants is not the same as monodisperse surfactant of the same average structure. This work provides a useful basis for the assessment of surfactant mixing by balancing their efficiency and toxicity.

Profound primary prevention of liver cancer following a natural experiment in China: A 50-year perspective and public health implications.

Liver cancer causes upwards of 1 million cancer deaths annually and is projected to rise by at least 55% over the next 15 years. Two of the major risk factors contributing to liver cancer have been well documented by multiple epidemiologic studies and the hepatitis B virus (HBV) and aflatoxin show a synergy that increases by more than 8-fold the risk of liver cancer relative to HBV alone. Using the population-based cancer registry established by the Qidong Liver Cancer Institute in 1972 and aflatoxin-specific biomarkers, we document that reduction of aflatoxin exposure has likely contributed to a nearly 70% decline in age-standardized liver cancer incidence over the past 30 years despite an unchanging prevalence of HBV infection in cases. A natural experiment of economic reform in the 1980s drove a rapid switch from consumption of heavily contaminated corn to minimally, if any, contaminated rice and subsequent dietary diversity. Aflatoxin consumption appears to accelerate the time to liver cancer diagnosis; lowering exposure to this carcinogen adds years of life before a cancer diagnosis. Thus, in 1990 the median age of diagnosis was 48 years, while increasing to 67 years by 2021. These findings have important translational public health implications since up to 5 billion people worldwide might be routinely exposed to dietary aflatoxin, especially in societies using corn as the staple food. Interventions against aflatoxin are an achievable outcome leading to a reduction in liver cancer incidence and years of delay of its nearly always fatal diagnosis.

Radiation-Emitting metallic stent for unresectable bismuth type III or IV perihilar cholangiocarcinoma: a multicenter randomized trial.

BACKGROUND AIMS: Self-expandable metallic stents (SEMSs) have been recommended for patients with unresectable malignant biliary obstruction while radiation-emitting metallic stents (REMSs) loaded with 125I seeds have recently been approved to provide longer patency and overall survival in malignant biliary tract obstruction. This trial is to evaluate the efficacy and safety of REMS plus hepatic arterial infusion chemotherapy (REMS-HAIC) versus SEMS plus HAIC (SEMS-HAIC) for unresectable perihilar cholangiocarcinoma (pCCA). METHODS: This multicenter randomized controlled trial recruited patients with unresectable Bismuth type III or IV pCCA between March 2021 and January 2023. Patients were randomly assigned (1:1 ratio) to receive either REMS-HAIC or SEMS-HAIC using permuted block randomization, with a block size of six. The primary endpoint was overall survival (OS). The secondary endpoints were time to symptomatic progression (TTSP), stent patency, relief of jaundice, quality of life, and safety. RESULTS: A total of 126 patients were included in the intent-to-treat population, with 63 in each group. The median OS was 10.2 months versus 6.7 months (P=0.002). The median TTSP was 8.6 months versus 5.4 months (P=0.003). The median stent patency was longer in the REMS-HAIC group than in the SEMS-HAIC group (P=0.001). The REMS-HAIC group showed better improvement in physical functioning scale (P<0.05) and fatigue symptoms (P<0.05) when compared to the SEMS-HAIC group. No significant differences were observed in relief of jaundice (85.7% vs. 84.1%; P=0.803) or the incidence of grade 3 or 4 adverse events (9.8% vs. 11.9%; P=0.721). CONCLUSION: REMS plus HAIC showed better OS, TTSP, and stent patency compared with SEMS plus HAIC in patients with unresectable Bismuth type III or IV pCCA with an acceptable safety profile.

Acoustic Controllable Spatiotemporal Cell Micro-oscillation for Noninvasive Intracellular Drug Delivery.

Intracellular cargo delivery is crucial for drug evaluation, nanomedicine development, and gene therapy, in which high efficiency while maintaining cell viability is needed for downstream analysis. Here, an acoustic-mediated precise drug delivering mechanism is proposed by directly modulating cell micro-oscillation mode and membrane permeability. Through phase shifting keying-based spatiotemporal acoustic tweezers, controllable oscillating cell arrays can be achieved in shaking potentials. At the same time, continually oscillating radiation force and fluid shear stress exerted on cells effectively disturbs cellular membrane mobility and enhances permeability, thereby facilitating nanodrug entrance. In experiments, cell oscillation is tunable in frequency (10-2 to 102 Hz), shaking direction, amplitude (0 to quarter acoustic wavelength), and speed. Doxorubicin is actively delivered across cellular membranes and accumulates in inner cells, with a concentration more than 8 times that of the control group. Moreover, there is no obvious compromise in cell activity during oscillation, exhibiting excellent biocompatibility. This "dancing acoustic waves" scheme introduces a new dimension of cell manipulation in both space and time domains and an effective drug delivering strategy, offering advantages of flexibility, gentleness, and high throughput. It may advance related fields like nanobiological research, drug and nanomedicine development, and medical treatment.

Theory-Guided Design of Unconventional Phase Metal Heteronanostructures for Higher-Rate Stable Li-CO2 and Li-Air Batteries.

Lithium-carbon dioxide (Li-CO2) and Li-air batteries hold great potential in achieving carbon neutral given their ultrahigh theoretical energy density and eco-friendly features. However, these Li-gas batteries still suffer from low discharging-charging rate and poor cycling life due to sluggish decomposition kinetics of discharge products especially Li2CO3. Here we report the theory-guided design and preparation of unconventional phase metal heteronanostructures as cathode catalysts for high-performance Li-CO2/air batteries. The assembled Li-CO2 cells with unconventional phase 4H/face-centered cubic (fcc) ruthenium-nickel heteronanostructures deliver a narrow discharge-charge gap of 0.65 V, excellent rate capability and long-term cycling stability over 200 cycles at 250 mA g-1. The constructed Li-air batteries can steadily run for above 150 cycles in ambient air. Electrochemical mechanism studies reveal that 4H/fcc Ru-Ni with high-electroactivity facets can boost redox reaction kinetics and tune discharge reactions towards Li2C2O4 path, alleviating electrolyte/catalyst failures induced by the aggressive singlet oxygen from solo decomposition of Li2CO3.

Genome-wide impact of codon usage bias on translation optimization in Drosophila melanogaster.

Accuracy and efficiency are fundamental to mRNA translation. Codon usage bias is widespread across species. Despite the long-standing association between optimized codon usage and improved translation, our understanding of its evolutionary basis and functional effects remains limited. Drosophila is widely used to study codon usage bias, but genome-scale experimental data are scarce. Using high-resolution mass spectrometry data from Drosophila melanogaster, we show that optimal codons have lower translation errors than nonoptimal codons after accounting for these biases. Genomic-scale analysis of ribosome profiling data shows that optimal codons are translated more rapidly than nonoptimal codons. Although we find no long-term selection favoring synonymous mutations in D. melanogaster after diverging from D. simulans, we identify signatures of positive selection driving codon optimization in the D. melanogaster population. These findings expand our understanding of the functional consequences of codon optimization and serve as a foundation for future investigations.

A New Perspective on Stroke Research: Unraveling the Role of Brain Oxygen Dynamics in Stroke Pathophysiology.

Stroke, a leading cause of death and disability, often results from ischemic events that cut off the brain blood flow, leading to neuron death. Despite treatment advancements, survivors frequently endure lasting impairments. A key focus is the ischemic penumbra, the area around the stroke that could potentially recover with prompt oxygenation; yet its monitoring is complex. Recent progress in bioluminescence-based oxygen sensing, particularly through the Green enhanced Nano-lantern (GeNL), offers unprecedented views of oxygen fluctuations in vivo. Utilized in awake mice, GeNL has uncovered hypoxic pockets within the cerebral cortex, revealing the brain's oxygen environment as a dynamic landscape influenced by physiological states and behaviors like locomotion and wakefulness. These findings illuminate the complexity of oxygen dynamics and suggest the potential impact of hypoxic pockets on ischemic injury and recovery, challenging existing paradigms and highlighting the importance of microenvironmental oxygen control in stroke resilience. This review examines the implications of these novel findings for stroke research, emphasizing the criticality of understanding pre-existing oxygen dynamics for addressing brain ischemia. The presence of hypoxic pockets in non-stroke conditions indicates a more intricate hypoxic scenario in ischemic brains, suggesting strategies to alleviate hypoxia could lead to more effective treatments and rehabilitation. By bridging gaps in our knowledge, especially concerning microenvironmental changes post-stroke, and leveraging new technologies like GeNL, we can pave the way for therapeutic innovations that significantly enhance outcomes for stroke survivors, promising a future where an understanding of cerebral oxygenation dynamics profoundly informs stroke therapy.

Regiocontrollable B(2/3)-H Alkenylation of nido-Carboranes.

Anionic nido-carboranes, as open-cage analogues of closo-carboranes with strong hydrophilicity and higher potential in the development of biomedicines, have been notably more challenging because of their strong interaction with transition metals. While the exo-cage B-H activation reactions of nido-carboranes have been widely studied, there are few reports on the direct functionalization of B-H bonds located on a closed polyhedral sphere. Here, we report an efficient palladium-catalyzed regioselective B(2/3)-H alkenylation of nido-carboranes with various alkenes and alkyne coupling partners, enabled by 3-methylpyridine directing groups, to achieve a regiocontrollable functionalization of B(2/3)-H vertices over highly reactive exo-cage B11-H vertex in nido-carboranes.

Fluorine-lodged high-valent high-entropy layered double hydroxide for efficient, long-lasting zinc-air batteries.

Efficient and stable bifunctional oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) catalysts are urgently needed to unlock the full potential of zinc-air batteries (ZABs). High-valence oxides (HVOs) and high entropy oxides (HEOs) are suitable candidates for their optimal electronic structures and stability but suffer from demanding synthesis. Here, a low-cost fluorine-lodged high-valent high-entropy layered double hydroxide (HV-HE-LDH) (FeCoNi2F4(OH)4) is conveniently prepared through multi-ions co-precipitation, where F- are firmly embedded into the individual hydroxide layers. Spectroscopic detections and theoretical simulations reveal high valent metal cations are obtained in FeCoNi2F4(OH)4, which enlarge the energy band overlap between metal 3d and O 2p, enhancing the electronic conductivity and charge transfer, thus affording high intrinsic OER catalytic activity. More importantly, the strengthened metal-oxygen (M-O) bonds and stable octahedral geometry (M-O(F)6) in FeCoNi2F4(OH)4 prevent structural reorganization, rendering long-term catalytic stability. Furthermore, an efficient three-phase reaction interface with fast oxygen transportation was constructed, significantly improving the ORR activity. ZABs assembled with FeCoNi2F4(OH)4@HCC (hydrophobic carbon cloth) cathodes deliver a top performance with high round-trip energy efficiency (60.6% at 10 mA cm-2) and long-term stability (efficiency remains at 58.8% after 1050 charge-discharge cycles).

Emerging role of Jumonji domain-containing protein D3 in inflammatory diseases.

Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri-methylated groups from lysine 27 on histone 3 (H3K27me2/3). The erasure of these marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3's role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Stereoselective synthetic approach toward ß-trifluoromethyl vinyl ethers and diethers via reaction of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene with phenols.

A convenient method for synthesizing ß-trifluoromethyl vinyl ethers and diethers through the base-mediated C-O coupling of (E)-1,2-dichloro-3,3,3-trifluoroprop-1-ene and phenols has been developed. Remarkably, the present process shows perfect regioselective and stereoselective yield of the Z/E isomers for ß-trifluoromethyl vinyl ethers with high efficiency. Additionally, ß-trifluoromethyl vinyl diethers with identical/diverse phenoxy groups were also obtained and the regulation of the product configuration was achieved. These reactions feature transition-metal-free conditions, wide substrate scope, and atom economy.

[Clinical phenotype and genetic analysis of a rare case with 6p duplication and terminal deletion syndrome].

OBJECTIVE: To explore the genetic basis for a child with developmental delay and intellectual deficit (DD/ID). METHODS: A child who was admitted to the Maternal and Child Health Care Hospital of Longhua District of Shenzhen City on June 3, 2023 due to DD/ID, craniofacial malformations, and recurrent infections of upper respiratory tract was selected as the study subject. G-banded chromosomal karyotyping was carried out for the child and her parents. Low-depth genome-wide copy number variation sequencing (CNV-seq) and chromosomal microarray analysis (CMA) were used to screen for genome-wide copy number variations (CNV), and fluorescence in situ hybridization (FISH) was used to verify the origin of candidate CNV. RESULTS: The child, an 8-year-old girl, had featured unexplained growth and intellectual development delay, multiple craniofacial malformations, and recurrent infections of the upper respiratory tract. She was found to have a karyotype of 46,XX,der(6)add(6)(q23), while both of her parents were normal. Both CNV-seq and CMA showed that the child has harbored a 21.38 Mb interstitial duplication at 6p25.3p22.3 and a 0.78 Mb terminal deletion at 6p25. FISH verified that both the duplication and deletion had occurred de novo. CONCLUSION: The abnormal phenotype of the child may be attributed to the 6p duplication and terminal deletion.

Impact of lower limb movements on iliac vein stenting in iliac vein compression syndrome patients: insights from computational modeling.

Purpose: Iliac vein stenting is the primary treatment for patients with iliac vein compression syndrome (IVCS). However, post-stent placement, patients often experience in-stent restenosis and thrombosis. Despite this, the role of lower limb movements in the functioning of stents and veins in IVCS patients remains unclear. This study aimed to address this knowledge gap by developing a computational model using medical imaging techniques to simulate IVCS after stent placement. Methods: This research used a patient-specific model to analyze the effects of lower extremity exercises on hemodynamics post-stent placement. We conducted a comprehensive analysis to evaluate the impact of specific lower limb movements, including hip flexion, ankle movement and pneumatic compression on the hemo-dynamic characteristics within the treated vein. The analysis assessed parameters such as wall shear stress (WSS), oscillatory shear index (OSI), and residence time (RRT). Results: The results demonstrated that hip flexion significantly disrupts blood flow dynamics at the iliac vein bifurcation after stenting. Bilateral and left hip flexion were associated with pronounced regions of low WSS and high OSI at the iliac-vena junction and the stent segment. Additionally, active ankle exercise (AAE) and intermittent pump compression (IPC) therapy were found to enhance the occurrence of low WSS regions along the venous wall, potentially reducing the risk of thrombosis post-stent placement. Consequently, both active joint movements (hip and ankle) and passive movements have the potential to influence the local blood flow environment within the iliac vein after stenting. Conclusions: The exploration of the impact of lower limb movements on hemodynamics provides valuable insights for mitigating adverse effects associated with lower limb movements post iliac-stenting. Bilateral and left hip flexions negatively impacted blood flow, increasing thrombosis risk. However, active ankle exercise and intermittent pump compression therapies effectively improve the patency.

Association between obesity and sleep disorder in the elderly: evidence from NHANES 2005-2018.

Background: The available data exhibit inconsistent findings regarding the association between obesity and sleep problems among older adults. The objective of this study was to assess the potential association between obesity and sleep disorders in the older population. Methods: The data utilised in this cross-sectional investigation was obtained from the National Health and Nutritional Examination Survey (NHANES) conducted between 2005 and 2018. The study employed a multivariate logistic regression model and conducted subgroup analysis to evaluate the association between obesity and sleep disturbance. Results: The investigation consisted of 2,570 older people who provided complete information, out of which 324 individuals satisfied the criteria for sleep disturbance. The findings from the multivariable adjusted logistic regression model indicate that individuals in the overweight and normal weight groups exhibited decreased odds of experiencing sleep disorder, as evidenced by the adjusted odds ratios (AOR) of 0.46 (95% confidence interval [CI] = 0.34-0.61) and 0.33 (95% CI = 0.22-0.47), respectively. These results were statistically significant (p < 0.001) when compared to individuals in the obese group. The investigation of age and gender subgroups demonstrated similar associations between various BMI categories and sleep disorders in the older population. Conclusion: In summary, there exists a correlation between obesity and sleep disorders in the senior population. A significant association was observed between BMI and the likelihood of experiencing sleep disorders, indicating a dose-response relationship. Individuals with a higher BMI demonstrated a heightened likelihood of experiencing sleep disorders compared to those with a lower BMI.

Application Study of Neutralization Confirmatory Testing for Low Positive Hepatitis B Surface Antigen.

BACKGROUND: The high sensitivity of HBsAg quantitative tests has led to some challenges in the qualitative interpretation of weakly positive specimens. This study aimed to explore the clinical utility of neutralization confirma-tory testing for specimens with low positive hepatitis B surface antigen (HBsAg). METHODS: A retrospective analysis was conducted on outpatient and inpatient cases, from January 2021 to January 2022, at the Zhongshan City People's Hospital, Zhongshan. Confirmatory testing as well as enzyme-linked immunosorbent assay (ELISA) was applied to reanalyze 382 samples with low positive HBsAg detected by chemilumi-nescence microparticle immunoassay (CMIA). A retrospective analysis of hepatitis B serum markers, including e-antigen, e-antibody, and core antibody patterns, was also performed. RESULTS: When the HBsAg value ranged from 0.05 - 0.09 IU/mL, the positivity rate of the confirmatory testing was 34.5%. The HBsAg true positivity levels were all between 0.07 and 0.09. In the range of 0.10 - 0.49, the positivity rate of confirmatory testing was 96.1%. The three methods exhibited a high consistency, when testing samples with relatively high HBsAg values. A receiver operating characteristic (ROC) analysis showed that the optimal sensitivity and specificity were achieved at 0.14 IU/mL. For the HBV e-antigen-positive and negative groups, the positivity rate of confirmatory testing was 100% and 93.8%, with no statistical difference between them. CONCLUSIONS: For specimens with weakly positive, low-value HBsAg, particularly when the hepatitis B surface an-tigen level is less than 0.14 IU/mL, neutralization confirmatory testing can serve as a means for further confirmation.

Unraveling the role of ubiquitin-conjugating enzyme 5 (UBC5) in disease pathogenesis: A comprehensive review.

While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)-a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction-has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands.