Tocilizumab attenuates choroidal neovascularization by regulating macrophage polarization through the IL-6R/STAT3/VEGF pathway.

Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV.

Three-Component Radical Cross-Coupling: Asymmetric Vicinal Sulfonyl-Esterification of Alkenes Involving Sulfur Dioxide.

A novel catalytic system for radical cross-coupling reactions based on copper and chiral Pyridyl-bis(imidazole) (PyBim) ligands is described. It overcomes the challenges of chemoselectivity and enantioselectivity, achieving a highly enantioselective vicinal sulfonyl-esterification reaction of alkenes involving sulfur dioxide. This strategy involves the use of earth-abundant metal catalyst, mild reaction conditions, a broad range of substrates (84 examples), high yields (up to 97% yield), and exceptional control over enantioselectivity. The reaction system is compatible with different types of radical precursors, including O-acylhydroxylamines, cycloketone oxime esters, aryldiazonium salts, and drug molecules. Chiral ligand PyBim is identified as particularly effective in achieving the desired high enantioselectivity. Mechanistic studies reveal that copper/PyBim system plays a vital role in C─O coupling, employing an outer-sphere model. In addition, the side arm effect of ligand is observed.

Seasonal variation in structural and functional distribution of periphyton in a macrolide antibiotics-contaminated river.

Periphyton, a microbial assemblage of autotrophic and heterotrophic organisms, is vital to aquatic ecosystems. While exposure to macrolide antibiotics has been confirmed to reduce the biodiversity and damage the critical ecological functions in indoor microcosm bioassays, the distribution of periphyton along a macrolide antibiotic pollution gradient in a river has yet to be determined. Herein, we established the spatiotemporal distribution of five major macrolides, i.e., azithromycin (AZI), roxithromycin (ROX), erythromycin (ERY), clarithromycin (CLA), and anhydro erythromycin (ERY-H2O) in water and periphyton of Zao River (Xi'an, China), after which we evaluated the effects on the structures, photosynthetic activity, and carbon utilization capacity of periphyton in March, June, and September 2023. In contrast with the reference sites, the macrolides were identified in all sewage treatment plants (STPs) impacted sites with concentrations ranging from 0.05 to 2.18 µg/L in water and from not detected - 9.67 µg/g in periphyton. Regarding community structure, the occurrence of macrolides was negatively linked to FirmicutesExiguobacterium undae and Exiguobacterium sibiricum, CyanobacteriaOscillatoriales and Vischeria sp., and ChlorophytaMonostroma grevillei, Selenastrum sp. LU21 and Desmodesmus subspicatus. At the functional level, only the metabolism of phenolic acids was significantly decreased in river reach with high antibiotic levels in June, compared to the other five carbon sources that were not altered. The overall photosynthetic activity of periphytic photosystem II remained unchanged in both reference and STPs impacted groups throughout three seasons. Overall, the macrolides released from STPs were correlated with the altered periphytic structures in the river, whereas a similar trend was not detected for the community functions owing to the functional redundancy. A mesocosm experiments warrants further consideration to validate the field results.

Porous Organic Polymers as Active Electrode Materials for Energy Storage Applications.

Eco-friendly and efficient energy production and storage technologies are highly demanded to address the environmental and energy crises. Porous organic polymers (POPs) are a class of lightweight porous network materials covalently linked by organic building blocks, possessing high surface areas, tunable pores, and designable components and structures. Due to their unique structural and compositional advantages, POPs have recently emerged as promising electrode materials for energy storage devices, particularly in the realm of supercapacitors and ion batteries. In this work, a comprehensive overview of recent progress and applications of POPs as electrode materials in energy storage devices, including the structural features and synthesis strategies of various POPs, as well as their applications in supercapacitors, lithium batteries, sodium batteries, and potassium batteries are provided. Finally, insights are provided into the future research directions of POPs in electrochemical energy storage technologies. It is anticipated that this work can provide readers with a comprehensive background on the design of POPs-based electrode materials and ignite more research in the development of next-generation energy storage devices.

CAPNet: Context attention pyramid network for computer-aided detection of microcalcification clusters in digital breast tomosynthesis.

BACKGROUND AND OBJECTIVE: Computer-aided detection (CADe) of microcalcification clusters (MCs) in digital breast tomosynthesis (DBT) is crucial in the early diagnosis of breast cancer. Although convolutional neural network (CNN)-based detection models have achieved excellent performance in medical lesion detection, they are subject to some limitations in MC detection: 1) Most existing models employ the feature pyramid network (FPN) for multi-scale object detection; however, the rough feature sharing between adjacent layers in the FPN may limit the detection ability for small and low-contrast MCs; and 2) the MCs region only accounts for a small part of the annotation box, so the features extracted indiscriminately within the whole box may easily be affected by the background. In this paper, we develop a novel CNN-based CADe method to alleviate the impacts of the above limitations for the accurate and rapid detection of MCs in DBT. METHODS: The proposed method has two parts: a novel context attention pyramid network (CAPNet) for intra-layer MC detection in two-dimensional (2D) slices and a three-dimensional (3D) aggregation procedure for aggregating 2D intra-layer MCs into a 3D result according to their connectivity in 3D space. The proposed CAPNet is based on an anchor-free and one-stage detection architecture and contains a context feature selection fusion (CFSF) module and a microcalcification response (MCR) branch. The CFSF module can efficiently enrich shallow layers' features by the complementary selection of local context features, aiming to reduce the missed detection of small and low-contrast MCs. The MCR branch is a one-layer branch parallel to the classification branch, which can alleviate the influence of the background region within the annotation box on feature extraction and enhance the ability of the model to distinguish MCs from normal breast tissue. RESULTS: We performed a comparison experiment on an in-house clinical dataset with 648 DBT volumes, and the proposed method achieved impressive performance with a sensitivity of 91.56 % at 1 false positive per DBT volume (FPs/volume) and 93.51 % at 2 FPs/volume, outperforming other representative detection models. CONCLUSIONS: The experimental results indicate that the proposed method is effective in the detection of MCs in DBT. This method can provide objective, accurate, and quick diagnostic suggestions for radiologists, presenting potential clinical value for early breast cancer screening.

Persulfidation maintains cytosolic G6PDs activity through changing tetrameric structure and competing cysteine sulfur oxidation under salt stress in Arabidopsis and tomato.

Glucose-6-phosphate dehydrogenases (G6PDs) are essential regulators of cellular redox. Hydrogen sulfide (H2 S) is a small gasotransmitter that improves plant adaptation to stress; however, its role in regulating G6PD oligomerization to resist oxidative stress remains unknown in plants. Persulfidation of cytosolic G6PDs was analyzed by mass spectrometry (MS). The structural change model of AtG6PD6 homooligomer was built by chemical cross-linking coupled with mass spectrometry (CXMS). We isolated AtG6PD6C159A and SlG6PDCC155A transgenic lines to confirm the in vivo function of persulfidated sites with the g6pd5,6 background. Persulfidation occurs at Arabidopsis G6PD6 Cystine (Cys)159 and tomato G6PDC Cys155, leading to alterations of spatial distance between lysine (K)491-K475 from 42.0 Å to 10.3 Å within the G6PD tetramer. The structural alteration occurs in the structural NADP+ binding domain, which governs the stability of G6PD homooligomer. Persulfidation enhances G6PD oligomerization, thereby increasing substrate affinity. Under high salt stress, cytosolic G6PDs activity was inhibited due to oxidative modifications. Persulfidation protects these specific sites and prevents oxidative damage. In summary, H2 S-mediated persulfidation promotes cytosolic G6PD activity by altering homotetrameric structure. The cytosolic G6PD adaptive regulation with two kinds of protein modifications at the atomic and molecular levels is critical for the cellular stress response.

Microplastic pollution in typical seasonal rivers in northern China: temporal variation and risk assessment.

Rivers are important channels for the transport of microplastics (MPs) from land to sea. In this work, the temporal variation and risk assessment of MP pollution in the surface water of the Wei River, a typical seasonal river in northern China, were quantified. The number abundance of MPs in the dry season was significantly higher than that in the wet season (p < 0.05). Fiber was the most abundant type of MP in both dry and wet seasons. Infrared spectrometer and Raman spectroscopy identification showed that polypropylene (PP) and polyethylene (PE) were the major polymers found in both dry and wet seasons, and the mixture of different MP polymers was more diverse in the dry season. The risk assessment showed that the average pollution load index (PLI) and risk quotient (RQ) were 2.10 and 1.19 in the dry season, which significantly decreased to 1.25 and 0.74, respectively, in the wet season (p < 0.05). In total, the results from this study highlight the characteristics of seasonal rivers that influence the temporal distribution and risk assessment of microplastics, providing scientific reference for policymakers and river managers to effectively deal with MP pollution.

Distribution, Sources, and Risk Assessment of Organochlorine Pesticides in Water from Beiluo River, Loess Plateau, China.

The Loess Plateau has been a focus of public discussion and environmental concerns over the past three decades. In this study, in order to investigate the effect of OCP pollution in water of the Beiluo River, concentrations of 25 OCPs at 17 locations in the water were examined. The results showed that the concentration of ∑OCPs in the water ranged from 1.76 to 32.57 ng L-1, with an average concentration of 7.23 ng L-1. Compared with other basins in China and abroad, the OCP content in the Beiluo River was at a medium level. Hexachlorocyclohexane (HCH) pollution in the Beiluo River was mainly from the mixed input of lindane and technical HCHs. Dichlorodiphenyltrichloroethane (DDT) pollution was mainly from the mixed input of technical DDTs and dicofol. Most of the OCP pollution came from historical residues. The risk assessment results showed that hexachlorobenzene (HCB) and endosulfan had high ecological risks in the middle and lower reaches of the Beiluo River. Most residual OCPs were not sufficient to pose carcinogenic and non-carcinogenic health risks to humans. The results of this study can provide a reference for OCP prevention and control and watershed environmental management.

Hydrogen sulfide improves salt tolerance through persulfidation of PMA1 in Arabidopsis.

KEY MESSAGE: A new interaction was found between PMA1 and GRF4. H2S promotes the interaction through persulfidated Cys446 of PMA1. H2S activates PMA1 to maintain K+/Na+ homeostasis through persulfidation under salt stress. Plasma membrane H+-ATPase (PMA) is a transmembrane transporter responsible for pumping protons, and its contribution to salt resistance is indispensable in plants. Hydrogen sulfide (H2S), a small signaling gas molecule, plays the important roles in facilitating adaptation of plants to salt stress. However, how H2S regulates PMA activity remains largely unclear. Here, we show a possible original mechanism for H2S to regulate PMA activity. PMA1, a predominant member in the PMA family of Arabidopsis, has a non-conservative persulfidated cysteine (Cys) residue (Cys446), which is exposed on the surface of PMA1 and located in cation transporter/ATPase domain. A new interaction of PMA1 and GENERAL REGULATORY FACTOR 4 (GRF4, belongs to the 14-3-3 protein family) was found by chemical crosslinking coupled with mass spectrometry (CXMS) in vivo. H2S-mediated persulfidation promoted the binding of PMA1 to GRF4. Further studies showed that H2S enhanced instantaneous H+ efflux and maintained K+/Na+ homeostasis under salt stress. In light of these findings, we suggest that H2S promotes the binding of PMA1 to GRF4 through persulfidation, and then activating PMA, thus improving the salt tolerance of Arabidopsis.

Occurrence of OCPs & PCBs and their effects on multitrophic biological communities in riparian groundwater of the Beiluo River, China.

Persistent Organic Pollutants (POPs) may exert adverse effects on human and ecosystem health. However, as an ecologically fragile zone with strong interaction between river and groundwater, the POPs pollution in the riparian zone has received little attention. The goal of this research is to examine the concentrations, spatial distribution, potential ecological risks, and biological effects of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in the riparian groundwater of the Beiluo River, China. The results showed that the pollution level and ecological risk of OCPs in riparian groundwater of the Beiluo River were higher than PCBs. The presence of PCBs (Penta-CBs, Hexa-CBs) and CHLs, respectively, may have reduced the richness of bacteria (Firmicutes) and fungi (Ascomycota). Furthermore, the richness and Shannon's diversity index of algae (Chrysophyceae and Bacillariophyta) decreased, which could be linked to the presence of OCPs (DDTs, CHLs, DRINs), and PCBs (Penta-CBs, Hepta-CBs), while for metazoans (Arthropoda) the tendency was reversed, presumably as a result of SULPHs pollution. In the network analysis, core species belonging to bacteria (Proteobacteria), fungi (Ascomycota), and algae (Bacillariophyta) played essential roles in maintaining community function. Burkholderiaceae and Bradyrhizobium can be considered biological indicators of PCBs pollution in the Beiluo River. Note that the core species of interaction network, playing a fundamental role in community interactions, are strongly affected by POPs pollutants. This work provides insights into the functions of multitrophic biological communities in maintaining the stability of riparian ecosystems through the response of core species to riparian groundwater POPs contamination.

Heterocyclic Boron Acid Catalyzed Dehydrative Amidation of Aliphatic/Aromatic Carboxylic Acids with Amines.

A commercially available and versatile dehydrative amidation catalyst, featuring a thianthrene boron acid structure, has been developed. The catalyst shows high catalytic activity to both aliphatic and less reactive aromatic carboxylic acid substrates, including several bioactive or clinical molecules with a carboxylic acid group.

Spatiotemporal variations of water conservation function based on EOF analysis at multi time scales under different ecosystems of Heihe River Basin.

Water conservation function is a critical terrestrial ecosystem service in providing water supply and achieving water security, which has raised concerns under the pressure of climate change. However, the knowledge of variance on multi-time scale, spatiotemporal dynamic, and ecosystem variance of water conservation is insufficient. In this paper, the annual, monthly, and daily scales of water conservation and the spatiotemporal pattern of monthly water conservation were estimated based on the SWAT model from 2010 to 2020 in the Heihe River Basin (HRB). Additionally, EOF (Empirical orthogonal function) analysis was conducted to decompose the time series of water conservation function distribution into temporal coefficients and spatial patterns. The HRB was categorized into six representative ecosystems with three slope grades to illustrate the variance of water conservation function. The annual water conservation depth (WC) slightly decreased (-10.36 mm/10a) from 2010 to 2020, the monthly WC was dominated by the effects of seasonal variation, and the daily WC was highly nonlinear. The high variability and importance region is mainly located in the upstream and the central area of midstream, which deserves more attention for ecological management and priority protection. Moreover, the forest ecosystem is of the highest resilience and great ecological significance, which increased risk of reduced water conservation under the lack of precipitation. Even in a forest-dominated basin, water conservation can be impacted by other ecosystems with the strong influence of human activities. Our results provide scientific evidence for the improvement of water conservation capacity and making the adapted land use policy in Yellow River basins.

Chimeric mRNA-based COVID-19 vaccine induces protective immunity against Omicron and Delta variants.

The emerging SARS-CoV-2 variants of concern (VOCs) exhibit enhanced transmission and immune escape, reducing the effectiveness of currently approved mRNA vaccines. To achieve wider coverage of VOCs, we first constructed a cohort of mRNAs harboring a furin cleavage mutation in the spike (S) protein of predominant VOCs, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). The mutation abolished the cleavage between the S1 and S2 subunits. Systematic evaluation in vaccinated mice discovered that individual VOC mRNAs elicited strong neutralizing activity in a VOC-specific manner. In particular, the neutralizing antibodies (nAb) produced by immunization with Beta-Furin and Washington (WA)-Furin mRNAs showed potent cross-reactivity with other VOCs. However, neither mRNA elicited strong neutralizing activity against the Omicron variant. Hence, we further developed an Omicron-specific mRNA vaccine that restored protection against the original Omicron variant and some sublineages. Finally, to broaden the protection spectrum of the new Omicron mRNA vaccine, we engineered an mRNA-based chimeric immunogen by introducing the receptor-binding domain of Delta variant into the entire S antigen of Omicron. The resultant chimeric mRNA induced potent and broadly nAbs against Omicron and Delta, which paves the way to developing new vaccine candidates to target emerging variants in the future.

SAH-NET: Structure-Aware Hierarchical Network for Clustered Microcalcification Classification in Digital Breast Tomosynthesis.

Benign and malignant classification of clustered microcalcifications (MCs) in digital breast tomosynthesis (DBT) is an essential task in computer-aided diagnosis. However, due to the anisotropic resolution of DBT, three-dimensional (3-D) convolutional neural network (CNN)-based methods cannot extract hierarchical features efficiently. Moreover, the sparse distribution of MC points in the cluster makes it difficult for the CNN to extract discriminative structural information for classification. To comprehensively address these challenges, we propose a novel structure-aware hierarchical network (SAH-Net) for benign and malignant classification of clustered MC in a DBT volume. Specifically, the two-dimensional (2-D) group convolution is used to extract intraslice features. The one-to-one correspondence between group convolutions and slices ensures the independence of hierarchical feature extraction. Then, a partial deformable Transformer-based 3-D structural feature learning module is proposed to capture the long-range dependency between MC points in the cluster. We evaluate the proposed method on an in-house dataset with 495 clustered MCs collected from 462 DBT images. Experimental results confirm the validity of our proposed modules. The results also show that the proposed SAH-Net outperforms several other representative methods on this topic, and achieves the best classification result, with an area under the receiver operation curve (AUC) of 86.87%. The implementation of the proposed model is available at https://github.com/sunhaotian130911/SAHNet.

Solvent-Controlled Regioselective Reaction of 2-Methyleneaziridines with Acrylic/Propargylic Acids: Synthesis of Carboxylate Aziridine/Acetone Esters.

Herein, we report a convenient solvent-controlled regioselective esterification to access two types of carboxylate esters without any additive or non-green activation strategy. In this transformation, 2-methyleneaziridines served as an ester reagent, providing two alternative electrophilic carbon centers. Notably, this protocol is suitable for some structure-complicated clinical molecules with a carboxylic acid group, presenting remarkable application potential.

Precise Polishing and Electrochemical Applications of Quartz Nanopipette-Based Carbon Nanoelectrodes.

Quartz nanopipette-based carbon nanoelectrodes (CNEs) have attracted extensive attention in nanoscale electrochemistry due to their simple and efficient fabrication, chemically inert materials, flexible size (down to a few nanometers), and ultrathin insulating encapsulation. However, these pristine CNEs usually have significantly irregular morphology on the surface, which greatly limits the applications where inlaid nanodisks are urgently needed. To address this critical issue, we have developed a new precise polishing strategy using paraffin coating protection (i.e., avoiding breakage of quartz materials) and real-time monitoring with a high impedance meter (i.e., indicating electrode exposure) to produce flat carbon nanodisk electrodes. The surface flatness of polished CNEs has been confirmed by a combination of scanning electron microscopy, fast-scan cyclic voltammetry, and scanning electrochemical microscopy. As compared to the expensive focused ion beam processing, this strategy is competitive in terms of the low cost and availability of the equipment and enables the preparation of polished CNEs with sufficiently small size. The flattened CNEs have been exemplified for grafting molecular catalysts to achieve the durable catalysis of reactive molecules or for immobilizing single-particle electrocatalysts to measure the intrinsic activity under sufficient mass-transfer rates.

The impacts of China's crops trade on virtual water flow and water use sustainability of the "Belt and Road".

Since the "Belt and Road" initiative was put forward, the trade of crops between China and the countries have increased markedly. Agriculture is the most water-consuming sector, the trade of crops could influence national water availability via virtual water embodied in the products. In order to gain an in-depth understanding of the water use of crops traded in countries along the "Belt and Road", from the perspective of import and export of China's crops, based on the characteristics and driving factors of virtual water trade, we proposed the Water Use Potential Index (WUPI) to assess sustainability of countries and their crops, and constructed a more comprehensive virtual water trade research framework. Results showed that the import and export of virtual water in 64 countries was dominated by green virtual water content from 2001 to 2017, and China was in a virtual water trade surplus. The Association of South-East Asian Nations was China's leading importer and exporter. The level of agricultural available water resources, the proportion of the agricultural population, the scale of agricultural production and the virtual water intensity could promote the growth of virtual water trade in crops between China and countries along the "Belt and Road", while economic model and the population structure played a restraining role. In terms of water use potential, China and Kazakhstan had great sustainable water use potential for crops, and the trade structure of other countries still needed to be further optimized. Understanding the virtual water trade in crops can provide a reference for the rational planning of crop cultivation and water resource conservation.

Assessment of biological community in riparian zone contaminated by PAHs: Linking source apportionment to biodiversity.

Riparian zone, an important land-water interface, plays an essential role in maintaining the ecological health of rivers, whereas the effects of Polycyclic aromatic hydrocarbons (PAHs) on the health of biological communities in riparian groundwater remain undetermined. To understand the responses of multiple communities to environmental variables, the distribution and ecosystem risk of 16 PAHs have been investigated in the Beiluo River, China. The distribution of multiple communities in riparian groundwater was investigated by environmental DNA metabarcoding, including 16S rRNA, 18S rRNA, and COI gene sequencing for bacteria, microbial eukaryotes (including algae, fungi, and protozoa), and metazoan, respectively, followed by correlation analysis between multiple communities and PAH contamination levels. The concentration of PAHs in the Beiluo River ranged largely from 35.32 to 728.59 ng/L. Here, the Shannon's diversity index of bacteria (Firmicutes) decreased possibly due to the occurrence of Pyrene, which mainly derives from coal and biomass combustion. Furthermore, the reduced richness of fungi (Ascomycota, Basidiomycota) and algae (Chlorophyta, Chrysophyceae) can be attributed to the presence of medium molecular weight (MMW) PAHs (Pyrene, Benz(a)anthracene, Chrysene), and low molecular weight (LMW) PAHs (Naphthalene, Fluorene, Phenanthrene). The richness and Shannon's diversity index of metazoan (Arthropoda) were promoted owing to MMW PAHs (Chrysene, Fluoranthene) generated from coal and biomass combustion and traffic emission. The ecological risk of PAHs in the groundwater environment of the Beiluo River was characterized as low to medium, where LMW and MMW PAHs posed higher risk than the high molecular weight (HMW) compounds. Overall, this study provides insights into the structures of riparian multi-biological communities altered by PAHs.

Comparative study on the manually-controlled variable-rate versus fixed-rate infusion of norepinephrine for preventing hypotension during spinal anesthesia for cesarean delivery.

STUDY OBJECTIVE: Previous studies have shown that prophylactic norepinephrine infusion is superior to intermittent bolus administration in preventing post-spinal hypotension. Nevertheless, it is still controversial whether manually-controlled variable-rate infusion is more effective than fixed-rate infusion. The purpose of the present study was to compare the efficacy of variable-rate infusion and fixed-rate infusion of norepinephrine for prophylaxis against maternal hypotension and maintaining hemodynamic stability during spinal anesthesia for cesarean delivery to determine more effective mode for clinical practice. DESIGN: A prospective randomized, controlled study. SETTING: Operating room, Women's Hospital, Zhejiang University School of Medicine. PATIENTS: A total of 161 parturients scheduled for elective cesarean delivery with spinal anesthesia were randomized into Group F (fixed-rate infusion) and Group V (variable-rate infusion). INTERVENTIONS: Parturients received prophylactic norepinephrine infusion concurrent with the intrathecal injection at rate started at 0.05 µg/kg/min. In Group F, norepinephrine was administered continuously at a fixed (on-off) rate, and a bolus of norepinephrine 5 µg or 10 µg was given when systolic blood pressure (SBP) decreased by 20% or more of baseline. In Group V, manually adjusted norepinephrine infusion within the range 0-0.14 µg/kg/min, according to SBP at 1-min intervals until delivery, aim to maintain values close to the baseline. MEASUREMENTS: During the study period, the incidence of maternal hypotension, hemodynamic performance, the number of physician interventions, reactive hypertension, bradycardia, nausea, vomiting, norepinephrine cumulative dose (before delivery), and neonatal outcomes were recorded. MAIN RESULTS: The incidence of maternal hypotension was significantly lower in Group V than that in Group F (9% versus 30%) (P < 0.001). No significant difference was found in the serial changes in SBP and heart rate (HR) for the first 15 min. Group V showed higher frequency of physician interventions compared with the Group F (P < 0.001). The incidence of hypertension, severe hypotension, nausea, vomiting, bradycardia, norepinephrine cumulative dose, and neonatal outcome were comparable between the two groups. CONCLUSION: When norepinephrine was infused at an initial dose of 0.05 µg/kg/min for preventing hypotension during spinal anesthesia for cesarean delivery, due to technical limitations of inadequate dose design in this study, neither a variable-rate infusion (need more physician intervention) nor a fixed-rate infusion regimen (experience more transient hypotension) was optimal. However, in terms of clinical importance, how to prevent the parturients from experiencing more incidence of hypotension might be a greater concern for anesthesiologists.

Polymyxin E biomineralized and doxorubicin-loaded gold nanoflowers nanodrug for chemo-photothermal therapy.

Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV-Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.