Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Attention-ProNet: A Prototype Network with Hybrid Attention Mechanisms Applied to Zero Calibration in Rapid Serial Visual Presentation-Based Brain-Computer Interface.

The rapid serial visual presentation-based brain-computer interface (RSVP-BCI) system achieves the recognition of target images by extracting event-related potential (ERP) features from electroencephalogram (EEG) signals and then building target classification models. Currently, how to reduce the training and calibration time for classification models across different subjects is a crucial issue in the practical application of RSVP. To address this issue, a zero-calibration (ZC) method termed Attention-ProNet, which involves meta-learning with a prototype network integrating multiple attention mechanisms, was proposed in this study. In particular, multiscale attention mechanisms were used for efficient EEG feature extraction. Furthermore, a hybrid attention mechanism was introduced to enhance model generalization, and attempts were made to incorporate suitable data augmentation and channel selection methods to develop an innovative and high-performance ZC RSVP-BCI decoding model algorithm. The experimental results demonstrated that our method achieved a balance accuracy (BA) of 86.33% in the decoding task for new subjects. Moreover, appropriate channel selection and data augmentation methods further enhanced the performance of the network by affording an additional 2.3% increase in BA. The model generated by the meta-learning prototype network Attention-ProNet, which incorporates multiple attention mechanisms, allows for the efficient and accurate decoding of new subjects without the need for recalibration or retraining.

Characterization of the fludioxonil and phenamacril dual resistant mutants of Fusarium graminearum.

Fusarium graminearum is an important fungal pathogen causing Fusarium head blight (FHB) in wheat and other cereal crops worldwide. Due to lack of resistant wheat cultivars, FHB control mainly relies on application of chemical fungicides. Both fludioxonil (a phenylpyrrole compound) and phenamacril (a cyanoacrylate fungicide) have been registered for controlling FHB in China, however, fludioxonil-resistant isolates of F. graminearum have been detected in field. To evaluate the potential risk of dual resistance of F. graminearum to both compounds, fludioxonil and phenamacril dual resistant (DR) mutants of F. graminearum were obtained via fungicide domestication in laboratory. Result showed that resistance of the DR mutants to both fludioxonil and phenamacril were genetically stable after sub-cultured for ten generations or stored at 4 °C for 30 days on fungicide-free PDA. Cross-resistance assay showed that the DR mutants remain sensitive to other groups of fungicides, including carbendazim, tebuconazole, pydiflumetofen, and fluazinam. In addition, the DR mutants exhibited defects in mycelia growth, conidiation, mycotoxin deoxynivalenol (DON) production, and virulence Moreover, the DR mutants displayed increased sensitivity to osmotic stress. Sequencing results showed that amino acid point mutations S217L/T in the myosin I protein is responsible for phenamacril resistance in the DR mutants. Our results indicate that mutations leading to fludioxonil and phenamacril dual resistance could result in fitness cost for F. graminearum. Our results also suggest that the potential risk of F. graminearum developing resistance to both fludioxonil and phenamacril in field could be rather low, which provides scientific guidance in controlling FHB with fludioxonil and phenamacril.

A Bionic Thermosensitive Sustainable Delivery System for Reversing the Progression of Osteoarthritis by Remodeling the Joint Homeostasis.

Although the pathogenesis of osteoarthritis (OA) is unclear, inflammatory cytokines are related to its occurrence. However, few studies focused on the therapeutic strategies of regulating joint homeostasis by simultaneously remodeling the anti-inflammatory and immunomodulatory microenvironments. Fibroblast growth factor 18 (FGF18) is the only disease-modifying OA drug (DMOAD) with a potent ability and high efficiency in maintaining the phenotype of chondrocytes within cell culture models. However, its potential role in the immune microenvironment remains unknown. Besides, information on an optimal carrier, whose interface and chondral-biomimetic microenvironment mimic the native articular tissue, is still lacking, which substantially limits the clinical efficacy of FGF18. Herein, to simulate the cartilage matrix, chondroitin sulfate (ChS)-based nanoparticles (NPs) are integrated into poly(D, L-lactide)-poly(ethylene glycol)-poly(D, L-lactide) (PLEL) hydrogels to develop a bionic thermosensitive sustainable delivery system. Electrostatically self-assembled ChS and ε-poly-l-lysine (EPL) NPs are prepared for the bioencapsulation of FGF18. This bionic delivery system suppressed the inflammatory response in interleukin-1ß (IL-1ß)-mediated chondrocytes, promoted macrophage M2 polarization, and inhibited M1 polarization, thereby ameliorating cartilage degeneration and synovitis in OA. Thus, the ChS-based hydrogel system offers a potential strategy to regulate the chondrocyte-macrophage crosstalk, thus re-establishing the anti-inflammatory and immunomodulatory microenvironment for OA therapy.

The jet-like chromatin structure defines active secondary metabolism in fungi.

Eukaryotic genomes are spatially organized within the nucleus in a nonrandom manner. However, fungal genome arrangement and its function in development and adaptation remain largely unexplored. Here, we show that the high-order chromosome structure of Fusarium graminearum is sculpted by both H3K27me3 modification and ancient genome rearrangements. Active secondary metabolic gene clusters form a structure resembling chromatin jets. We demonstrate that these jet-like domains, which can propagate symmetrically for 54 kb, are prevalent in the genome and correlate with active gene transcription and histone acetylation. Deletion of GCN5, which encodes a core and functionally conserved histone acetyltransferase, blocks the formation of the domains. Insertion of an exogenous gene within the jet-like domain significantly augments its transcription. These findings uncover an interesting link between alterations in chromatin structure and the activation of fungal secondary metabolism, which could be a general mechanism for fungi to rapidly respond to environmental cues, and highlight the utility of leveraging three-dimensional genome organization in improving gene transcription in eukaryotes.

Beyond pathways: Accelerated flavonoids candidate identification and novel exploration of enzymatic properties using combined mapping populations of wheat.

Although forward-genetics-metabolomics methods such as mGWAS and mQTL have proven effective in providing myriad loci affecting metabolite contents, they are somehow constrained by their respective constitutional flaws such as the hidden population structure for GWAS and insufficient recombinant rate for QTL. Here, the combination of mGWAS and mQTL was performed, conveying an improved statistical power to investigate the flavonoid pathways in common wheat. A total of 941 and 289 loci were, respectively, generated from mGWAS and mQTL, within which 13 of them were co-mapped using both approaches. Subsequently, the mGWAS or mQTL outputs alone and their combination were, respectively, utilized to delineate the metabolic routes. Using this approach, we identified two MYB transcription factor encoding genes and five structural genes, and the flavonoid pathway in wheat was accordingly updated. Moreover, we have discovered some rare-activity-exhibiting flavonoid glycosyl- and methyl-transferases, which may possess unique biological significance, and harnessing these novel catalytic capabilities provides potentially new breeding directions. Collectively, we propose our survey illustrates that the forward-genetics-metabolomics approaches including multiple populations with high density markers could be more frequently applied for delineating metabolic pathways in common wheat, which will ultimately contribute to metabolomics-assisted wheat crop improvement.

A novel complement C3 inhibitor CP40-KK protects against experimental pulmonary arterial hypertension via an inflammasome NLRP3 associated pathway.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary disease characterized by complement dependent and proinflammatory activation of macrophages. However, effective treatment for complement activation in PAH is lacking. We aimed to explore the effect and mechanism of CP40-KK (a newly identified analog of selective complement C3 inhibitor CP40) in the PAH model. METHODS: We used western blotting, immunohistochemistry, and immunofluorescence staining of lung tissues from the monocrotaline (MCT)-induced rat PAH model to study macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Surface plasmon resonance (SPR), ELISA, and CH50 assays were used to test the affinity between CP40-KK and rat/human complement C3. CP40-KK group rats only received CP40-KK (2 mg/kg) by subcutaneous injection at day 15 to day 28 continuously. RESULTS: C3a was significantly upregulated in the plasma of MCT-treated rats. SPR, ELISA, and CH50 assays revealed that CP40-KK displayed similar affinity binding to human and rat complement C3. Pharmacological inhibition of complement C3 cleavage (CP40-KK) could ameliorate MCT-induced NLRP3 inflammasome activity, pulmonary vascular remodeling, and right ventricular hypertrophy. Mechanistically, increased proliferation of pulmonary arterial smooth muscle cells is closely associated with macrophage infiltration, NLPR3 inflammasome activation, and proinflammatory cytokines (IL-1ß and IL-18) release. Besides, C3a enhanced IL-1ß activity in macrophages and promoted pulmonary arterial smooth muscle cell proliferation in vitro. CONCLUSION: Our findings suggest that CP40-KK treatment was protective in the MCT-induced rat PAH model, which might serve as a therapeutic option for PAH.

Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis.

The aim of this study is to investigate whether there is a correlation between serum calcium levels and clinical severity or functional outcome at discharge in Chinese patients with acute ischemic stroke. Data from 339 patients admitted to our hospital between July 2020 and July 2021 were analyzed. Baseline demographic and clinical information was collected within 24 h of admission, including serum calcium levels, stroke severity (measured by the National Institutes of Health Stroke Scale [NIHSS] score), and lesion volumes. The modified Rankin Scale [mRS] assessed functional outcomes at discharge. Our analysis showed that the median age of patients included in the study was 65 years (interquartile range [IQR], 60-70), and 60.8% were men. We found a positive correlation between serum calcium levels and stroke severity (r[spearman] = 0.266, P < 0.001), with calcium levels increasing as stroke severity increased. In a subgroup of 188 patients with available MRI data, serum calcium concentrations positively correlated with infarct size. Furthermore, in multivariate analysis, a calcium serum level in the highest quartile was associated with a higher risk of unfavorable outcome (odds ratios [OR] = 3.27; 95% confidence intervals [CI] = 1.91-5.59; P < 0.001). In conclusion, our study indicates that higher calcium serum levels are associated with stroke severity and early neurologic outcome after acute ischemic stroke, indicating that calcium may serve as a prognostic biomarker for stroke in Chinese patients.

NCOA5 Haploinsufficiency in Myeloid-Lineage Cells Sufficiently Causes Nonalcoholic Steatohepatitis and Hepatocellular Carcinoma.

BACKGROUND & AIMS: The nuclear receptor coactivator 5 (NCOA5) is a putative type 2 diabetes susceptibility gene. NCOA5 haploinsufficiency results in the spontaneous development of nonalcoholic fatty liver disease (NAFLD), insulin resistance, and hepatocellular carcinoma (HCC) in male mice; however, the cell-specific effect of NCOA5 haploinsufficiency in various types of cells, including macrophages, on the development of NAFLD and HCC remains unknown. METHODS: Control and myeloid-lineage-specific Ncoa5 deletion (Ncoa5ΔM/+) mice fed a normal diet were examined for the development of NAFLD, nonalcoholic steatohepatitis (NASH), and HCC. Altered genes and signaling pathways in the intrahepatic macrophages of Ncoa5ΔM/+ male mice were analyzed and compared with those of obese human individuals. The role of platelet factor 4 (PF4) in macrophages and the underlying mechanism by which PF4 affects NAFLD/NASH were explored in vitro and in vivo. PF4 expression in HCC patient specimens and prognosis was examined. RESULTS: Myeloid-lineage-specific Ncoa5 deletion sufficiently causes spontaneous NASH and HCC development in male mice fed a normal diet. PF4 overexpression in Ncoa5ΔM/+ intrahepatic macrophages is identified as a potent mediator to trigger lipid accumulation in hepatocytes by inducing lipogenesis-promoting gene expression. The transcriptome of intrahepatic macrophages from Ncoa5ΔM/+ male mice resembles that of obese human individuals. High PF4 expression correlated with poor prognosis of HCC patients and increased infiltrations of M2 macrophages, regulatory T cells, and myeloid-derived suppressor cells in HCCs. CONCLUSIONS: Our findings reveal a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC.

AAV-mediated delivery of a Sleeping Beauty transposon and an mRNA-encoded transposase for the engineering of therapeutic immune cells.

Engineering cells for adoptive therapy requires overcoming limitations in cell viability and, in the efficiency of transgene delivery, the duration of transgene expression and the stability of genomic integration. Here we report a gene-delivery system consisting of a Sleeping Beauty (SB) transposase encoded into a messenger RNA delivered by an adeno-associated virus (AAV) encoding an SB transposon that includes the desired transgene, for mediating the permanent integration of the transgene. Compared with lentiviral vectors and with the electroporation of plasmids of transposon DNA or minicircle DNA, the gene-delivery system, which we named MAJESTIC (for 'mRNA AAV-SB joint engineering of stable therapeutic immune cells'), offers prolonged transgene expression, as well as higher transgene expression, therapeutic-cell yield and cell viability. MAJESTIC can deliver chimeric antigen receptors (CARs) into T cells (which we show lead to strong anti-tumour activity in vivo) and also transduce natural killer cells, myeloid cells and induced pluripotent stem cells with bi-specific CARs, kill-switch CARs and synthetic T-cell receptors.

ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis.

Neuroinflammation plays critical roles in vascular dementia (VaD), the second leading cause of dementia, which can be induced by chronic cerebral hypoperfusion (CCH). NLRP3 inflammasome-induced pyroptosis, the inflammatory programmed cell death, has been reported to contribute to the development of VaD. ChemR23 is a G protein-coupled receptor that has emerging roles in regulating inflammation. However, the role of ChemR23 signalling in NLRP3 inflammasome-induced pyroptosis in CCH remains elusive. In this study, a CCH rat model was established by permanent bilateral common carotid artery occlusion (BCCAO) surgery. Eight weeks after the surgery, the rats were intraperitoneally injected with the ChemR23 agonist Resolvin E1 (RvE1) or chemerin-9 (C-9). Additionally, primary rat hippocampal neurons and SH-SY5Y cells were adopted to mimic CCH injury in vitro. Our results showed that the levels of ChemR23 expression were decreased from the 8th week after BCCAO, accompanied by significant cognitive impairment. Further analysis revealed that CCH induced neuronal damage, synaptic injury and NLRP3-related pyroptosis activation in hippocampal neurons. However, pharmacologic activation of ChemR23 with RvE1 or C-9 counteracted these changes. In vitro experiments also showed that ChemR23 activation prevented primary neuron pyroptosis induced by chronic hypoxia. In addition, manipulating ChemR23 expression markedly regulated NLRP3 inflammasome-induced neuronal pyroptosis through PI3K/AKT/Nrf2 signalling in SH-SY5Y cells under hypoglycaemic and hypoxic conditions. Collectively, our data demonstrated that ChemR23 activation inhibits NLRP3 inflammasome-induced neuronal pyroptosis and improves cognitive function via the PI3K/AKT/Nrf2 signalling pathway in CCH models. ChemR23 may serve as a potential novel therapeutic target to treat CCH-induced cognitive impairment.

Case report: Recurrent pontine stroke and leukoencephalopathy in a patient with de novo mutation in COL4A1.

This report presents a case of pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) in a 35 year-old male patient. The patient exhibited a consistent history of recurrent ischemic strokes, concentrated primarily in the pons region, accompanied by concurrent manifestations of leukoencephalopathy and microbleeds. Genetic evaluation revealed a heterozygous missense mutation consistent with c.3431C>G, p. Thr1144Arg substitution within exon 40 of the COL4A1 gene. This mutation was also identified in the patient's mother, affirming an autosomal dominant inheritance model. Our findings serve as testament to the potential role of mutation in the exon 40 of COL4A1 in the pathogenesis and progression of PADMAL, contributing to ongoing efforts aimed at better understanding the genetic basis of this debilitating disorder.

The transcription factor FgStuA regulates virulence and mycotoxin biosynthesis via recruiting the SAGA complex in Fusarium graminearum.

The conserved Spt-Ada-Gcn5-Acetyltransferase (SAGA) complex controls eukaryotic transcription by modifying acetylation of histones. However, the mechanisms for this complex in regulating the transcription of target-specific genes remain largely unknown in phytopathogenic fungi. A filamentous fungal-specific transcription factor FgStuA was identified to interact with the SAGA complex physically. The coordinative mechanisms of FgStuA with the SAGA complex in regulating secondary metabolism and virulence were investigated in Fusarium graminearum with genetic, biochemical and molecular techniques. The transcription factor FgStuA binds to a 7-bp cis-element (BVTGCAK) of its target gene promoter. Under mycotoxin deoxynivalenol (DON) induction conditions, FgStuA recruits the SAGA complex into the promoter of TRI6, a core regulator of the DON biosynthesis gene cluster, leading to enhanced transcription of TRI6. During this process, we found that FgStuA is subject to acetylation by the SAGA complex, and acetylation of FgStuA plays a critical role for its enrichment in the TRI6 promoter. In addition, FgStuA together with the SAGA complex modulates fungal virulence. This study uncovers a novel regulatory mechanism of a transcription factor, which recruits and interacts with the SAGA complex to activate specific gene expression in pathogenic fungi.

Icaritin ameliorates RANKL-mediated osteoclastogenesis and ovariectomy-induced osteoporosis.

A rapidly aging society and longer life expectancy are causing osteoporosis to become a global epidemic. Over the last five decades, a number of drugs aimed at reducing bone resorption or restoring bone mass have been developed, but their efficacy and safety are limited. Icaritin (ICT) is a natural compound extracted from anti-osteoporosis herb Epimedium spp. and has been shown to inhibit osteoclast differentiation. However, the molecular mechanism by which ICT weaken RANKL-induced osteoclast differentiation has not been completely investigated. Here, we evaluated the anti-osteoclastogenic effect of ICT in vitro and the potential drug candidate for treating osteoporosis in vivo. In vitro study, ICT was found to inhibit osteoclast formation and bone resorption function via downregulating transcription factors activated T cell cytoplasm 1 (NFATc1) and c-fos, which further downregulate osteoclastogenesis-specific gene. In addition, the enhanced mitochondrial mass and function required for osteoclast differentiation was mitigated by ICT. The histomorphological results from an in vivo study showed that ICT attenuated the bone loss associated with ovariectomy (OVX). Based on these results, we propose ICT as a promising new drug strategy for osteoporosis that inhibits osteoclast differentiation.

Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.

Sex differences in hepatocellular carcinoma (HCC) development are regulated by sex and non-sex chromosomes, sex hormones, and environmental factors. We previously reported that Ncoa5+/- mice develop HCC in a male-biased manner. Here we show that NCOA5 expression is reduced in male patient HCCs while the expression of an NCOA5-interacting tumor suppressor, TIP30, is lower in female HCCs. Tip30 heterozygous deletion does not change HCC incidence in Ncoa5+/- male mice but dramatically increases HCC incidence in Ncoa5+/- female mice, accompanied by hepatic hyperpolarization-activated cyclic nucleotide-gated cation channel 3 (HCN3) overexpression. HCN3 overexpression cooperates with MYC to promote mouse HCC development, whereas Hcn3 knockout preferentially hinders HCC development in female mice. Furthermore, HCN3 amplification and overexpression occur in human HCCs and correlate with a poorer prognosis of patients in a female-biased manner. Our results suggest that TIP30 and NCOA5 protect against female liver oncogenesis and that HCN3 is a female-biased HCC driver.

Daily walking kinematic characteristics of the elderly in different residential settings: experimental study on Chinese community-living elderly and long-term nursing home residents.

BACKGROUND: Long-term nursing home (NH) care helps NH residents with their daily activities and improves their quality of life, but negatively affects their independent physical activities and increases the risk of dangerous events. Dangerous events in the elderly usually occur in the conversion of walking periods when forward striding has already happened, but the body has not yet entered a completely steady walking. OBJECTIVES: Compare the gait characteristics in Chinese long-term NH residents and community-living elderly during the walking Transitional Period (TP) and Stabilization Period (SP). METHODS: 32 long-term NH residents and 33 age- and sex-matched community-living elderly were recruited. The 30-Second Chair Stand Test (30-s CST), Timed Up and Go Test (TUGT), and Modified Falls Efficacy Scale (MFES) were used to assess their body function. The Xsens MVN BIOMECH system was used to collect and analyze the gait parameters of participants. RESULTS: Compared to community-living elderly, NH residents had fewer numbers of 30-s CST, took more time to complete TUGT, and lower MEFS scores. NH residents showed slower gait speed (P < 0.001), less peak hip flexion (P = 0.022) and extension (P = 0.003), knee internal rotation (P = 0.023), and ankle plantarflexion (P = 0.001) and internal rotation (P = 0.007) angles during walking. When walking progressed from TP to SP, NH residents showed increased ankle dorsiflexion (P < 0.001), decreased hip internal rotation (P < 0.001), and community-living elderly had increased hip extension (P = 0.005) angles. CONCLUSIONS: Chinese long-term NH residents had reduced lower extremities strength and postural balance, and higher fear of falling compared to community-living elderly. Their walking performance also showed high fall risk. Besides, long-term NH residents adopted a distal strategy to propel the body forward, which may be a compensatory measure to compensate for inadequate proximal joint control from forward walking to stable walking, and long-term NH residents have reduced postural stability during this process.

Glycolytic enzyme PKM2 regulates cell senescence but not inflammation in the process of osteoarthritis.

Chondrocyte senescence is an important mechanism underlying osteoarthritis in the senile population and is characterized by reduced expressions of the extracellular matrix proteins. The involvement of glycolysis and the tricarboxylic acid cycle in the development of osteoarthritis is inclusive. The present study aims to investigate the role of the glycolytic enzyme M2 isoform of pyruvate kinase (PKM2) in chondrocytes in senescence and inflammation. Primary chondrocytes are isolated from the knee joints of neonatal mice. Small interfering RNAs (siRNAs) against PKM2 are transfected using lipofectamine. RNA sequencing is conducted in primary chondrocytes with the PKM2 gene deleted. Cell apoptosis, autophagy, reactive oxygen species measurement, and senescent conditions are examined. The glycolytic rate in cells is measured by Seahorse examination. Interleukin 1-ß (IL-1ß) increases the protein expressions of matrix metallopeptidases (MMP)13 and PKM2 and reduces the protein expression of collagen type II (COL2A1) in primary chondrocytes. Silencing of PKM2 alters the protein expressions of MMP13, PKM2, and COL2A1 in the same pattern in quiescent and stimulated chondrocytes. RNA sequencing analysis reveals that PKM2 silencing reduces senescent biomarker p16 INK4a expression. Compared with low-passage chondrocytes, high-passage chondrocytes exhibit increased expression of p16 INK4a and reduced expression of COL2A1. Silencing of PKM2 reduces SA-ß-Gal signals and increases COL2A1 expression in high-passage chondrocytes. Seahorse assay reveals that PKM2 deletion favors the tricarboxylic acid cycle in mitochondria in low- but not in high-passage chondrocytes. In summary, the glycolytic enzyme PMK2 modulates chondrocyte senescence but does not participate in the regulation of inflammation.

Subclavian vein ultrasound-guided fluid management to prevent post-spinal anesthetic hypotension during cesarean delivery: a randomized controlled trial.

BACKGROUND: Hypotension frequently occurs after spinal anesthesia during cesarean delivery, and fluid loading is recommended for its prevention. We evaluated the efficacy of subclavian vein (SCV) ultrasound (US)-guided volume optimization in preventing hypotension after spinal anesthesia during cesarean delivery. METHODS: This randomized controlled study included 80 consecutive full-term parturients scheduled for cesarean delivery under spinal anesthesia. The women were randomly divided into the SCVUS group, with SCVUS analysis before spinal anesthesia with SCVUS-guided volume management, and the control group without SCVUS assessment. The SCVUS group received 3 mL/kg crystalloid fluid challenges repeatedly within 3 min with a 1-min interval based on the SCV collapsibility index (SCVCI), while the control group received a fixed dose (10 mL/kg). Incidence of post-spinal anesthetic hypotension was the primary outcome. Total fluid volume, vasopressor dosage, changes in hemodynamic parameters, maternal adverse effects, and neonatal status were secondary outcomes. RESULTS: The total fluid volume was significantly higher in the control group than in the SCVUS group (690 [650-757.5] vs. 160 [80-360] mL, p < 0.001), while the phenylephrine dose (0 [0-40] vs. 0 [0-30] µg, p = 0.276) and incidence of post-spinal anesthetic hypotension (65% vs. 60%, p = 0.950) were comparable between both the groups. The incidence of maternal adverse effects, including nausea/vomiting and bradycardia (12.5% vs. 17.5%, p = 0.531 and 7.5% vs. 5%, p = 1.00, respectively), and neonatal outcomes (Apgar scores) were comparable between the groups. SCVCI correlated with the amount of fluid administered (R = 0.885, p < 0.001). CONCLUSIONS: SCVUS-guided volume management did not ameliorate post-spinal anesthetic hypotension but reduced the volume of the preload required before spinal anesthesia. Reducing preload volume did not increase the incidence of maternal and neonatal adverse effects nor did it increase the total vasopressor dose. Moreover, reducing preload volume could relieve the heart burden of parturients, which has high clinical significance. CLINICAL TRIAL REGISTRATION: The trial was registered with the Chinese Clinical Trial Registry at chictr.org.cn (registration number, ChiCTR2100055050) on December 31, 2021.

Metal 3D nanoprinting with coupled fields.

Metallized arrays of three-dimensional (3D) nanoarchitectures offer new and exciting prospects in nanophotonics and nanoelectronics. Engineering these repeating nanoarchitectures, which have dimensions smaller than the wavelength of the light source, enables in-depth investigation of unprecedented light-matter interactions. Conventional metal nanomanufacturing relies largely on lithographic methods that are limited regarding the choice of materials and machine write time and are restricted to flat patterns and rigid structures. Herein, we present a 3D nanoprinter devised to fabricate flexible arrays of 3D metallic nanoarchitectures over areas up to 4 × 4 mm2 within 20 min. By suitably adjusting the electric and flow fields, metal lines as narrow as 14 nm were printed. We also demonstrate the key ability to print a wide variety of materials ranging from single metals, alloys to multimaterials. In addition, the optical properties of the as-printed 3D nanoarchitectures can be tailored by varying the material, geometry, feature size, and periodic arrangement. The custom-designed and custom-built 3D nanoprinter not only combines metal 3D printing with nanoscale precision but also decouples the materials from the printing process, thereby yielding opportunities to advance future nanophotonics and semiconductor devices.

A novel strategy for bioaerosol rapid detection based on broad-spectrum high-efficiency magnetic enrichment and separation combined with ATP bioluminescence.

Bioaerosol detection technology represented by laser-induced fluorescence (LIF) cannot effectively detect bioaerosols in the presence of interferents such as plant-derived smoke, industrial waste gas, pollen and pollen debris which can produce strong non-biological fluorescence interference. To overcome this drawback, in this study, a novel method based on broad-spectrum high-efficiency magnetic enrichment and separation combined with adenosine triphosphate (ATP) bioluminescence was proposed for Escherichia coli (E. coli) bioaerosols rapid detection. First, E. coli bioaerosols mixed with interferents were collected. Core-shell Fe3O4@Polydopamine@Polyethyleneimine magnetic particles were used as bioaerosol enrichment materials to enrich E. coli bioaerosol sampling solutions. Subsequently, an ATP bioluminescence assay was performed to determine the concentration of E. coli. A linear relationship was observed between ATP bioluminescence intensity after enrichment and the E. coli bioaerosol concentration in the range of 870-49,098 particles per liter; the bioluminescence intensity measured after enrichment was significantly higher than that before enrichment, and this enrichment method provide a 6-fold better sensitivity in bioaerosol detection. More importantly, this method efficiently enriched and detected bioaerosols in plant-derived smoke. This method can effectively improve the sensitivity of ATP bioluminescence detection, and possesses the advantages of convenient operation and strong anti-interference ability. It also provides a foundation for the effective detection of bioaerosols mixed with interfering substances, and a reference for evaluating the sensitivity and anti-interference of LIF-based instruments.