Rapidly inducible yeast surface display for antibody evolution with OrthoRep.

We recently developed 'autonomous hypermutation yeast surface display' (AHEAD), a technology that enables the rapid generation of potent and specific antibodies in yeast. AHEAD pairs yeast surface display with an error-prone orthogonal DNA replication system (OrthoRep) to continuously and rapidly mutate surface-displayed antibodies, thereby enabling enrichment for stronger binding variants through repeated rounds of cell growth and fluorescence activated cell sorting (FACS). AHEAD currently utilizes a standard galactose induction system to drive the selective display of antibodies on the yeast surface. However, achieving maximal display levels can require up to 48 hours of induction. Here, we report an updated version of the AHEAD platform that utilizes a synthetic ß-estradiol induced gene expression system to regulate the surface display of antibodies and find that induction is notably faster in achieving surface display for both our AHEAD system as well as traditional yeast surface display from nuclear plasmids that do not hypermutate. The updated AHEAD platform was fully functional in repeated rounds of evolution to drive the rapid evolution of antibodies.

Enhancing Molecular Energy Predictions with Physically Constrained Modifications to the Neural Network Potential.

Exclusively prioritizing the precision of energy prediction frequently proves inadequate in satisfying multifaceted requirements. A heightened focus is warranted on assessing the rationality of potential energy curves predicted by machine learning-based force fields (MLFFs), alongside evaluating the pragmatic utility of these MLFFs. This study introduces SWANI, an optimized neural network potential stemming from the ANI framework. Through the incorporation of supplementary physical constraints, SWANI aligns more cohesively with chemical expectations, yielding rational potential energy profiles. It also exhibits superior predictive precision compared with that of the ANI model. Additionally, a comprehensive comparison is conducted between SWANI and a prominent graph neural network-based model. The findings indicate that SWANI outperforms the latter, particularly for molecules exceeding the dimensions of the training set. This outcome underscores SWANI's exceptional capacity for generalization and its proficiency in handling larger molecular systems.

Awake Combined Spinal Caudal Anesthesia for Longer-Duration Urologic Surgery in Infants: A Case Series.

Awake combined spinal caudal anesthesia has been used as an anesthetic technique for longer-duration infraumbilical surgeries in infants. Literature on the safety and feasibility of this technique is limited. We share our experience with 27 infants undergoing longer-duration urologic surgery using awake combined spinal and caudal anesthesia without the use of systemic sedatives or inhalational agents. We describe our technique, safety considerations, and details surrounding the optimal timing of caudal catheter activation for prolongation of surgical anesthesia.

A highly sensitive ratiometric fluorescence probe for sensing and imaging sulfite in food samples and living cells.

In this work, a ratiometric and chromogenic fluorescent probe 1 was synthesized for the detection of SO32-. The probe 1 at PBS (10 mM, pH = 7.4) presented a marked emission band at 661 nm. Upon addition of SO32- ions, a highly emissive adduct with a marked fluorescence at 471 nm were obtained through a Michael addition. The probe 1 displayed a noticeable fluorescence ratiometric response with a large shift (190 nm) in emission wavelength. The probe can quantitatively detect SO32- with high specificity, fast response (within 130 s) as well as low detection limit (13 nM), and a large Stokes shift (139 nm). Fluorescence imaging of HeLa cells indicated that 1 could be used for monitoring the intrinsically generated intracellular SO32- in living cells by ratiometric fluorescence imaging. Furthermore, 1 could be application in real water and sugar samples with high sensitivity and good recoveries.

Effectiveness of home-based cardiac telerehabilitation based on wearable ECG or heart rate monitoring devices in patients with heart disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

[Consumption status and growth trends of dairy products among children and adolescents in China from 1991 to 2018].

OBJECTIVE: To explore the dairy consumption among children and adolescents aged 7-17 in China. METHODS: 10 rounds of follow-up data from the "China Health and Nutrition Survey" from 1991 to 2018 were collected, and individuals aged 7-17 were selected as the study subjects. Dietary data was collected by using 3-day 24-hour dietary review method and household weighing accounting method(edible oils and seasonings). Dairy consumption was calculated by converting various dairy products into liquid milk intake using the China Food Composition. After excluding those with missing demographic information, missing data from the "3 days and 24 hours" dietary survey, and abnormal daily energy intake, 18 529 participants were included in the final analysis. Joinpoint regression model was used to analyze the trend of changes in dairy intake. RESULTS: The dairy consumption rate increased from 2.8% in 1991 to 42.3% in 2018, while it increased from 8.4% to 58.8% in urban and from 0.9% to 32.1% in rural areas. Meanwhile, the proportion of people whose dairy intake reaches the recommended intake(300 g/d) increased from 0.2% to 3.0%, and the proportion in rural area was 2.0%, which was lower than that in urban areas(4.9%). From 1991 to 2018, dairy intake increased at a rate of 12.97%(P=0.02), and the growth rate of urban and rural areas were 9.79%(P=0.03) and 15.67%(P<0.01), respectively. There was a faster growth trend from 1991-2004 compared to 2004-2018. The growth rate in urban and rural areas also showed different growth trends. CONCLUSION: The dairy intake of children and adolescents aged 7-17 in China improved significantly from 1991 to 2018, with higher consumption rate in urban areas than in rural areas, but it still need to be improved for health.

Low GPR81 in ER+ breast cancer cells drives tamoxifen resistance through inducing PPARα-mediated fatty acid oxidation.

AIMS: The intricate molecular mechanisms underlying estrogen receptor-positive (ER+) breast carcinogenesis and resistance to endocrine therapy remain elusive. In this study, we elucidate the pivotal role of GPR81, a G protein-coupled receptor, in ER+ breast cancer (BC) by demonstrating low expression of GPR81 in tamoxifen (TAM)-resistant ER+ BC cell lines and tumor samples, along with the underlying molecular mechanisms. MAIN METHODS: Fatty acid oxidation (FAO) levels and lipid accumulation were explored using MDA and FAßO assay, BODIPY 493/503 staining, and Lipid TOX staining. Autophagy levels were assayed using CYTO-ID detection and Western blotting. The impact of GPR81 on TAM resistance in BC was investigated through CCK8 assay, colony formation assay and a xenograft mice model. RESULTS: Aberrantly low GPR81 expression in TAM-resistant BC cells disrupts the Rap1 pathway, leading to the upregulation of PPARα and CPT1. This elevation in PPARα/CPT1 enhances FAO, impedes lipid accumulation and lipid droplet (LD) formation, and subsequently inhibits cell autophagy, ultimately promoting TAM-resistant BC cell growth. Moreover, targeting GPR81 and FAO emerges as a promising therapeutic strategy, as the GPR81 agonist and the CPT1 inhibitor etomoxir effectively inhibit ER+ BC cell and tumor growth in vivo, re-sensitizing TAM-resistant ER+ cells to TAM treatment. CONCLUSION: Our data highlight the critical and functionally significant role of GPR81 in promoting ER+ breast tumorigenesis and resistance to endocrine therapy. GPR81 and FAO levels show potential as diagnostic biomarkers and therapeutic targets in clinical settings for TAM-resistant ER+ BC.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): A prospective, multicenter, randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. METHODS: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in post-inguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for four weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. RESULTS: Of the 1,109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2% vs. 6.00%, P<0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3% vs. 9.50%, P<0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P<0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/L vs. 0.35±0.55 mg/L, P=0.028). In the experimental group, the patients did not experience an increased risk of VTE (0% vs. 1.66%, P=0.268) and bleeding (1.18% vs. 0.67%, P=0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18% vs. 0.83%, P=0.559). CONCLUSION: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE. TRIAL REGISTRATION: XXX. TRIAL REGISTRATION: ChiCTR2000033769.

CRISPR-Cas9-mediated Editing of GmARM Improves Resistance to Multiple Stresses in Soybean.

The growth and development of soybean plants can be affected by both abiotic and biotic stressors, such as saline-alkali stress and Phytophthora root rot. In this study, we identified a stress-related gene-GmARM-whose promoter contained several hormone-response and stress-regulatory elements, including ABRE, TCA element, STRE, and MBS. qRT-PCR analysis showed that the expression of GmARM was the highest in seeds at 55 days after flowering. Furthermore, this gene was upregulated after exposure to saline-alkali stress and Phytophthora root rot infection at the seedling stage. Thus, we generated GmARM mutants using the CRISPR-Cas9 system to understand the role of this gene in stress response. T3 plants showed significantly improved salt tolerance, alkali resistance, and disease resistance, with a significantly higher survival rate than the wildtype plants. Moreover, mutations in GmARM affected the expression of related stress-resistance genes, indicating that GmARM mutants achieved multiple stress tolerance. Therefore, this study provides a foundation for further exploration of the genes involved in resistance to multiple stresses in soybean that can be used for breeding multiple stress-resistance soybean varieties.

Preparation of (3-Aminopropyl)triethoxysilane-Modified Silica Particles with Tunable Isoelectric Point.

Silica particles modified with amino groups hold immense potential across diverse fields, owing to their distinctive properties. The widely adopted method of surface modification, utilizing (3-aminopropyl)triethoxysilane (APTES), facilitates the incorporation of amino-functional groups onto the silica surface, thereby creating sites for subsequent functionalization with other molecules. In this context, the ability to precisely tailor the surface properties of amino-functionalized silica particles is crucial for optimizing their performance in various applications. In this work, we systematically investigated the influence of the APTES concentration and water content on the density of amino groups grafted on the silica surface within an ethanol-water mixture. The rational control of hydrolysis and condensation of APTES enabled the precise regulation of the amino density on the silica surface, resulting in a notable shift in the isoelectric point from 2.9 to 9.2. Subsequently, we assembled amino-functionalized silica with different isoelectric points with gold nanoparticles to demonstrate their tunable ability as surface-enhanced Raman scattering (SERS) substrates. This controlled and tailored amino-functionalization process opens up new routes for fine-tuning the properties of silica particles, thereby expanding their utility across various applications in materials science, nanotechnology, and biomedicine.

Biotemplated Fe/La-co-doped TiO2 for photocatalytic depth treatment of compressed leachate from refuse transfer station.

Compressed leachate is a contaminated liquid containing various organic and inorganic pollutants produced in municipal refuse transfer stations, which pollute soil and groundwater, posing serious risks to the environment and human health. The Environmental Technology Co., Ltd. (Shenzhen, Guangdong Province, South China) treated compressed leachate obtained from a refuse transfer station. The chemical oxygen demand (COD) (641.2 mg/L) of treated compressed leachate did not meet the wastewater quality standards in China for discharge into municipal sewers (COD ≤ 500 mg/L) and the company's design discharge requirements (COD ≤ 400 mg/L). Therefore, their further in-depth treatment is necessary. To this end, waste tobacco leaves were used as the biotemplate herein, and Fe/La-co-doped TiO2 (xFe,yLa)-TTiO2(g) was synthesized using a solvothermal-assisted biotemplating method. The photocatalytic depth treatment of compressed leachate was performed under simulated solar light using the prepared catalysts. After (3Fe,3La)-TTiO2(g) treatment, the COD of the leachate decreased from 641.2 to 280.1 mg/L, and the COD removal rate was 1.2, 1.1, and 1.6 times higher than that of pure Fe-doped, La-doped and non-biological template TiO2, respectively. Characterization confirmed that the biological template endowed the catalyst with a unique morphology and high specific surface area. Its rich activity sites are conducive to enhancing the adsorption capacity of pollutants and providing an ideal place for photocatalytic reactions. Co-doping with iron and lanthanum ions altered the band structure of TiO2 and promoted the interconversion of Fe3+/Fe2+ and La3+/La2+ during photocatalysis. First-principles density functional theory simulations demonstrated that co-doping Fe and La in TiO2 created impurity levels that facilitated the transfer of photogenerated electrons. This study provides a new purification pathway for the depth treatment of compressed leachate.

Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results.

Claudin18.2 (CLDN18.2) is highly expressed with the development of various malignant tumors, especially gastrointestinal cancers, and is emerging as a new target for cancer treatment. Satricabtagene autoleucel (satri-cel)/CT041 is an autologous chimeric antigen receptor (CAR) T cell targeting CLDN18.2, and the interim results of the CT041-CG4006 trial were reported in June 2022. Here we present the final results of this single-arm, open-label, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. This trial included a dose-escalation stage (n = 15) and a dose-expansion stage in four different cohorts (total n = 83): cohort 1, satri-cel monotherapy in 61 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 2, satri-cel plus anti-PD-1 therapy in 15 patients with standard chemotherapy-refractory gastrointestinal cancers; cohort 3, satri-cel as sequential treatment after first-line therapy in five patients with gastrointestinal cancers; and cohort 4, satri-cel monotherapy in two patients with anti-CLDN18.2 monoclonal antibody-refractory gastric cancer. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. A total of 98 patients received satri-cel infusion, among whom 89 were dosed with 2.5 × 108, six with 3.75 × 108 and three with 5.0 × 108 CAR T cells. Median follow-up was 32.4 months (95% confidence interval (CI): 27.3, 36.5) since apheresis. No dose-limiting toxicities, treatment-related deaths or immune effector cell-associated neurotoxicity syndrome were reported. Cytokine release syndrome occurred in 96.9% of patients, all classified as grade 1-2. Gastric mucosal injuries were identified in eight (8.2%) patients. The overall response rate and disease control rate in all 98 patients were 38.8% and 91.8%, respectively, and the median progression-free survival and overall survival were 4.4 months (95% CI: 3.7, 6.6) and 8.8 months (95% CI: 7.1, 10.2), respectively. Satri-cel demonstrates therapeutic potential with a manageable safety profile in patients with CLDN18.2-positive advanced gastrointestinal cancer. ClinicalTrials.gov identifier: NCT03874897 .

Semisynthesis and antitumor activity of endertiin B and related triterpenoids from Ganoderma lucidum.

Ganoderma lucidum, a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo. Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 µM and 12.12 ± 0.95 µM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.

WS2 ribbon arrays with defined chirality and coherent polarity.

One-dimensional transition metal dichalcogenides exhibiting an enhanced bulk photovoltaic effect have the potential to exceed the Shockley-Queisser limit efficiency in solar energy harvest within p-n junction architectures. However, the collective output of these prototype devices remains a challenge. We report on the synthesis of single-crystalline WS2 ribbon arrays with defined chirality and coherent polarity through an atomic manufacturing strategy. The chirality of WS2 ribbon was defined by substrate couplings into tunable armchair, zigzag, and chiral species, and the polarity direction was determined by the ribbon-precursor interfacial energy along a coherent direction. A single armchair ribbon showed strong bulk photovoltaic effect and the further integration of ~1000 aligned ribbons with coherent polarity enabled upscaling of the photocurrent.

Biological and molecular characterization of pydiflumetofen and phenamacril dual-resistant Fusarium graminearum strains.

BACKGROUND: Fusarium head blight (FHB) caused by Fusarium graminearum species complex (FGSG) remains a major challenge to cereal crops and resistance to key fungicides by the pathogen threatens control efficacy. Pydiflumetofen, a succinate dehydrogenase inhibitor, and phenamacril, a cyanoacrylate fungicide targeting myosin I, have been applied to combat this disease. Nonetheless, emergence of pydiflumetofen resistance in a subset of field isolates alongside laboratory-induced facile generation of phenamacril-resistant isolates signals a critical danger of resistance proliferation. RESULTS: Our study investigates the development of dual resistance to these fungicides in F. graminearum. Utilizing pydiflumetofen-resistant (PyR) and -sensitive (PyS) isolates, we obtained dual-resistant (PyRPhR) and phenamacril-resistant (PySPhR) mutants on potato sucrose agar containing phenamacril. Mutation rates for phenamacril resistance were comparable between pydiflumetofen-resistant and -sensitive isolates, implying independent pathways for resistance development. The mutants compromised in fungal growth, competitive viability and deoxynivalenol production, suggesting fitness penalties for the dual-resistant mutants. However, no cross-resistance was found with tebuconazole or fludioxonil. In addition, we characterized four critical amino acid changes (S217L, C423R, K537T, E420G) in the Myo1 that were verified to confer phenamacril resistance in F. graminearum. CONCLUSION: This research indicates the possibility of resistance development for both pydiflumetofen and phenamacril in F. graminearum and emphasizes the need for fungicide resistance management for FHB. © 2024 Society of Chemical Industry.

ZHypoalbuminemia contributes to ascites formation via sodium and water retention: Evidence from clinical date and albumin deficient mice.

Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl4)-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb+/-) mice (112.0 mg) was larger than that of wild-type (Alb+/+) mice (58.46 mg, P < 0.001). In CCl4-induced chronic liver injury, ascites amounts of Alb+/- or Alb+/+ mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb+/- mice was lower than that of Alb+/+ mice in TAA/CCl4-induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb+/- mice was lower than that of Alb+/+ mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb+/- mice compared with the control; and renal aquaporin (AQP2) expression in Alb+/- mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention.

Mechanisms linking physical activity with mental health in children and adolescents with neurodevelopmental disorders: A systematic review.

INTRODUCTION: Physical activity (PA) is a promising way to improve mental health in children and adolescents with neurodevelopmental disorders (NDDs). However, the underlying mechanisms remain unclear. The current review aimed to explore the potential neurobiological, psychosocial, and behavioral mechanisms between PA interventions and mental health in children and adolescents with NDDs. METHODS: Web of Science, PsycINFO, SPORTDiscus, MEDLINE, CINAHL, and ERIC were searched from inception to June 2023. Randomized controlled trials/quasi-experimental designs applying PA interventions and reporting at least one mental health outcome and at least one potential mechanism in children and adolescents with NDDs were included. The best evidence synthesis rating system (BESRS) was adopted to determine the strength and consistency of potential mechanisms and was performed in 2024. RESULTS: In total, 45 studies were included, 29 of which were randomized controlled trials and 16 were quasi-experimental, with a total of 1,751 participants. According to the BESRS, neurobiological (theta activity and P3 amplitude), psychosocial (social skills and social participation), and behavioral (motor skills and sleep) mechanisms were the frequently examined and consistent mechanisms through which PA affected mental health in children and adolescents with NDDs. However, evidence regarding P3 latency, beta activity, and physical self-concept was insufficient. DISCUSSION: Future PA interventions could consider neurobiological (theta activity and P3 amplitude), psychosocial (social skills and social participation), and behavioral (motor skills and sleep) mechanisms. Alternatively, PA can be developed as an adjunctive approach with interventions that specifically focus on these mechanisms to enhance mental health in children and adolescents with NDDs.

Repurposing of halogenated organic pollutants via alkyl bromide-catalysed transfer chlorination.

Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs.

Strong chiroptical nonlinearity in coherently stacked boron nitride nanotubes.

Nanomaterials with a large chiroptical response and high structural stability are desirable for advanced miniaturized optical and optoelectronic applications. One-dimensional (1D) nanotubes are robust crystals with inherent and continuously tunable chiral geometries. However, their chiroptical response is typically weak and hard to control, due to the diverse structures of the coaxial tubes. Here we demonstrate that as-grown multiwalled boron nitride nanotubes (BNNTs), featuring coherent-stacking structures including near monochirality, homo-handedness and unipolarity among the component tubes, exhibit a scalable nonlinear chiroptical response. This intrinsic architecture produces a strong nonlinear optical response in individual multiwalled BNNTs, enabling second-harmonic generation (SHG) with a conversion efficiency up to 0.01% and output power at the microwatt level-both excellent figures of merit in the 1D nanomaterials family. We further show that the rich chirality of the nanotubes introduces a controllable nonlinear geometric phase, producing a chirality-dependent SHG circular dichroism with values of -0.7 to +0.7. We envision that our 1D chiral platform will enable novel functions in compact nonlinear light sources and modulators.

Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: a bibliometric study and visual analysis.

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion: The last 4 decades have seen a notable rise in publications on lipid-lowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches.