Corrigendum: Bibliometric and visual analysis of machine learning-based research in acute kidney injury worldwide.

[This corrects the article DOI: 10.3389/fpubh.2023.1136939.].

Modeling multi-component separation in hydrophobic interaction chromatography with improved parameter-by-parameter estimation method.

Mechanistic models are powerful tools for chromatographic process development and optimization. However, hydrophobic interaction chromatography (HIC) mechanistic models lack an effective and logical parameter estimation method, especially for multi-component system. In this study, a parameter-by-parameter method for multi-component system (called as mPbP-HIC) was derived based on the retention mechanism to estimate the six parameters of the Mollerup isotherm for HIC. The linear parameters (ks,i and keq,i) and nonlinear parameters (ni and qmax,i) of the isotherm can be estimated by the linear regression (LR) and the linear approximation (LA) steps, respectively. The remaining two parameters (kp,i and kkin,i) are obtained by the inverse method (IM). The proposed method was verified with a two-component model system. The results showed that the model could accurately predict the protein elution at a loading of 10 g/L. However, the elution curve fitting was unsatisfactory for high loadings (12 g/L and 14 g/L), which is mainly attributed to the demanding experimental conditions of the LA step and the potential large estimation error of the parameter qmax. Therefore, the inverse method was introduced to further calibrate the parameter qmax, thereby reducing the estimation error and improving the curve fitting. Moreover, the simplified linear approximation (SLA) was proposed by reasonable assumption, which provides the initial guess of qmax without solving any complex matrix and avoids the problem of matrix unsolvable. In the improved mPbP-HIC method, qmax would be initialized by the SLA and finally determined by the inverse method, and this strategy was named as SLA+IM. The experimental validation showed that the improved mPbP-HIC method has a better curve fitting, and the use of SLA+IM reduces the error accumulation effect. In process optimization, the parameters estimated by the improved mPbP-HIC method provided the model with excellent predictive ability and reasonable extrapolation. In conclusion, the SLA+IM strategy makes the improved mPbP-HIC method more rational and can be easily applied to the practical separation of protein mixture, which would accelerate the process development for HIC in downstream of biopharmaceuticals.

The Chemokine CCL2 Promotes Excitatory Synaptic Transmission in Hippocampal Neurons via GluA1 Subunit Trafficking.

The CC chemokine ligand 2 (CCL2, also known as MCP-1) and its cognate receptor CCR2 have well-characterized roles in chemotaxis. CCL2 has been previously shown to promote excitatory synaptic transmission and neuronal excitability. However, the detailed molecular mechanism underlying this process remains largely unclear. In cultured hippocampal neurons, CCL2 application rapidly upregulated surface expression of GluA1, in a CCR2-dependent manner, assayed using SEP-GluA1 live imaging, surface GluA1 antibody staining, and electrophysiology. Using pharmacology and reporter assays, we further showed that CCL2 upregulated surface GluA1 expression primarily via Gαq- and CaMKII-dependent signaling. Consistently, using i.p. injection of lipopolysaccharide to induce neuroinflammation, we found upregulated phosphorylation of S831 and S845 sites on AMPA receptor subunit GluA1 in the hippocampus, an effect blocked in Ccr2-/- mice. Together, these results provide a mechanism through which CCL2, and other secreted molecules that signal through G-protein coupled receptors, can directly regulate synaptic transmission.

Fibroblasts: New players in the central nervous system?

Fibroblasts are typically described as cells that produce extracellular matrix, contribute to the formation of connective tissue, and maintain the structural framework of tissues. Fibroblasts are the first cell type to be transdifferentiated into inducible pluripotent stem cells (iPSCs), demonstrating their versatility and reprogrammability. Currently, there is relatively extensive characterization of the anatomical, molecular, and functional diversity of fibroblasts in different peripheral organs and tissues. With recent advances in single cell RNA sequencing, heterogeneity and diversity of fibroblasts in the central nervous system (CNS) have also begun to emerge. Based on their distinct anatomical locations in the meninges, perivascular space, and choroid plexus, as well as their molecular diversity, important roles for fibroblasts in the CNS have been proposed. Here, we draw inspirations from what is known about fibroblasts in peripheral tissues, in combination with their currently identified CNS locations and molecular characterizations, to propose potential functions of CNS fibroblasts in health and disease. Future studies, using a combination of technologies, will be needed to determine the bona fide in vivo functions of fibroblasts in the CNS.

Differential transcriptome study on the damage of testicular tissues caused by chronic infection of T. gondii in mice.

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue. METHODS: RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays. RESULTS: The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |log2fold change| â‰§ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes. CONCLUSIONS: Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system.

Simultaneous mitigation of heterocyclic aromatic amines and advanced glycation end products in roasted beef patties by plasma-activated water: Effects and mechanisms.

Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 µg/g, 297.74 ng/g, and 4.32 µg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.

Droplet Micro-Sensor and Detection of Respiratory Droplet Transmission.

Droplet transmission is the primary infection route for respiratory diseases like COVID-19 and influenza, but small and low-cost wearable droplet detection devices are a significant challenge. Herein, a respiratory droplet micro-sensor based on graphene oxide quantum dots (GOQDs) assembled onto SiO2 microspheres by the nebulized natural deposition is presented. Benefiting from the energy dissipation of the microsphere to droplets, the sensor can detect droplets as far as 2 m from coughing. With this sensor, droplet signal variations caused by some factors like distance, speech, angles, and wind directions are explored, and the effectiveness of different protective measures in preventing droplet transmission is evaluated. This droplet detection technology is expected to be utilized for the development of personal detection and protection devices against infectious respiratory diseases.

Comparison of "Huaxi-1" or "histidine-tryptophan-ketoglutarate" cardioplegia in an animal model.

Background: Using a pig model of cardiopulmonary bypass, we compared outcomes after cardioplegia either with our in-house "Huaxi-1" solution containing natural blood and crystalloid or with the entirely crystalloid, commercially available "histidine-tryptophan-ketoglutarate" solution. Methods: Cardiopulmonary bypass was established in 12 healthy male pigs, who were randomized to receive a single dose of either Huaxi-1 or entirely crystalloid. All animals were then subjected to whole-heart ischemia for 90 min, followed by 2 h of reperfusion, after which myocardial injury was assessed in terms of cardiac function, myocardial pathology and levels of biomarkers in plasma, while levels of high-energy phosphate in myocardium were assayed using liquid chromatography. Results: Animals given Huaxi-1 cardioplegia required significantly less time to be weaned off bypass, they received significantly lower doses of norepinephrine, and they showed significantly higher levels (mean ± SD) of adenosine triphosphate (14 ± 4 vs. 8 ± 2 µg/mg, P = 0.005), adenosine diphosphate (16 ± 2 vs. 13 ± 2 µg/mg, P = 0.046), and total adenine nucleotide (37 ± 4 vs. 30 ± 3 µg/mg, P = 0.006) in myocardium after 2 h of reperfusion. They also showed less severe bleeding, edema and injury to mitochondria and myofibers in myocardium. The two groups did not differ significantly in doses of inotropic drugs received, cardiac output or levels of biomarkers in plasma. Conclusions: In this animal model of healthy hearts subjected to 90 min of ischemia, Huaxi-1 cardioplegia may be superior to entirely crystalloid cardioplegia for promoting energy generation and attenuating ischemia/reperfusion injury in myocardium.

Real-ambient bedroom light at night increases systemic inflammation and disrupts circadian rhythm of inflammatory markers.

BACKGROUND: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. OBJECTIVES: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. METHODS: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5 lx, 10 LANavg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. RESULTS: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. CONCLUSION: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.

Macrocyclic Neutralizer to Polybrene via Direct Host-Guest Complexation.

Hexadimethrine bromide (HB), a synthetic polycationic species, was introduced to clinical practice as a heparin antidote and recently used in gene therapy. However, HB causes various complications such as severe red blood cells (RBCs) aggregation and tissue damage. Herein, we have synthesized a water-soluble quaterphen[3]arene containing multiple sulfonate moieties (SQP3) as a novel macrocyclic neutralizer to reverse HB via direct host-guest complexation. SQP3 exhibited a robust binding affinity toward HB with a considerably high association constant of (4.73 ± 0.61) × 107 M-1. Co-dosed with 1 equiv of SQP3, HB-induced RBCs aggregation and blood coagulation could be effectively reversed. In vitro cellular assay verified that complexation of HB with SQP3 significantly decreased reactive oxygen species production, thereby suppressing cell apoptosis. In vivo neutralization efficacy studies demonstrated that HB/SQP3 was capable of alleviating related organic damage caused by HB and improving the survival rate of HB-treated mice from 20 to 100%.

Harnessing Quantum Capacitance in 2D Material/Molecular Layer Junctions for Novel Electronic Device Functionality.

Two-dimensional (2D) materials promise advances in electronic devices beyond Moore's scaling law through extended functionality, such as non-monotonic dependence of device parameters on input parameters. However, the robustness and performance of effects like negative differential resistance (NDR) and anti-ambipolar behavior have been limited in scale and robustness by relying on atomic defects and complex heterojunctions. In this paper, we introduce a novel device concept that utilizes the quantum capacitance of junctions between 2D materials and molecular layers. We realized a variable capacitance 2D molecular junction (vc2Dmj) diode through the scalable integration of graphene and single layers of stearic acid. The vc2Dmj exhibits NDR with a substantial peak-to-valley ratio even at room temperature and an active negative resistance region. The origin of this unique behavior was identified through thermoelectric measurements and ab initio calculations to be a hybridization effect between graphene and the molecular layer. The enhancement of device parameters through morphology optimization highlights the potential of our approach toward new functionalities that advance the landscape of future electronics.

Electroacupuncture Facilitates Vascular Normalization by Inhibiting Glyoxalase1 in Endothelial Cells to Attenuate Glycolysis and Angiogenesis in Triple-Negative Breast Cancer.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

Linearization of wavelength sweeping lasers for the construction of 4-D FMCW LiDAR images of slow-moving objects using baseband beat note signals.

A FMCW LiDAR system of both the distributed feedback laser and external cavity laser is established in baseband beat notes, rather than up-conversion to an intermediate frequency to exclude flicker noise. Meanwhile, utilizing fast-scanning MEMS mirrors, high-quality real-time (1 fps) 4-D images of the slow-moving object (10 mm/s) can be directly constructed at the baseband with a central frequency as low as 100 kHz and a small Doppler shift. The proposed LiDAR architecture based on such a low-frequency baseband significantly improves the optical power budget on the transmitter side and eliminates the costly high-speed sampling circuits on the receiver side.

Artificial intelligence iterative reconstruction in abdominal CT of patients with irregular arm positioning: a case-by-case evaluation.

BACKGROUND: Streak artifacts induced by irregular arm positioning have been an issue in diagnosing the abdomen. PURPOSE: To illustrate the risk of misdiagnosis in abdominal computed tomography (CT) of patients with irregular arm positioning through a case-by-case evaluation and to test if it can be solved by the artificial intelligence iterative reconstruction (AIIR) algorithm. MATERIAL AND METHODS: By reviewing 5220 cases of chest and thoracoabdominal CT, 64 patients with irregular arm positioning were enrolled, whose image data were reconstructed using AIIR in addition to routine hybrid iterative reconstruction (HIR). Lesion detection for livers, spleens, kidneys, gallbladders, and pancreas on AIIR images, performed by two radiologists, was compared with those on HIR images. Discrepancies arising from AIIR images included both cases with additional abnormalities and those with corrections made on previous detections. For cases with discrepancies, artifact scores for organs where discrepancies were found, and contrast-to-noise ratios (CNRs) of cysts with discrepancies were compared between two image sets. RESULTS: Additional abnormalities were detected for 15 cases: additional liver cirrhosis (n=2); additional gallbladder stone (n=1); additional cholecystitis (n=1), additional spleen nodule (n=1); additional kidney cysts (n=8); additional liver cysts (3); and additional spleen cyst (n=1). A spleen contusion was corrected for one case. All involved artifact scores were improved on AIIR images. CNRs of involved liver, kidney, and spleen cysts were improved by up to 539.7%, 538.5%, and 245.5%, respectively. CONCLUSION: Irregular arm positioning may induce a variety of misdiagnoses in abdominal CT, which is almost totally avoidable by the AIIR algorithm.

Engineered AAV13 variants with enhanced transduction and confined spread.

Precise targeting of specific regions within the central nervous system (CNS) is crucial for both scientific research and gene therapy in the context of brain diseases. Adeno-associated virus 13 (AAV13) is known for its restricted diffusion range within the CNS, making it an ideal choice for precise labeling and administration within small brain regions. However, AAV13 mediates relatively low expression of target genes. Here, we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction efficiency. We first constructed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 capsid. We then inserted the 7m8 peptide, known to enhance cell transduction, into positions 587/588 and 585/586 of the AAV13 capsid, resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8, respectively. We found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells compared to AAV13, while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice, with AAV13-587-7m8 infection retaining a limited spread range. These modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

Expedient access to polysubstituted acrylamides via strain-release-driven dual phosphine and palladium catalysis.

Polysubstituted acrylamides are ubiquitous in bioactive molecules and natural products. However, synthetic methods for the assembly of these important motifs remain underdeveloped. Herein, we report the expedient synthesis of structurally diverse and synthetically challenging polysubstituted acrylamides from readily available aromatic amines, cyclopropenones (CpOs), and aryl halides via the synergistic merging of nucleophilic phosphine-mediated amidation and palladium-catalyzed C-H arylation. The reaction is scalable, and some obtained acrylamides proved to be solid state luminogens with obvious aggregation-induced emission (AIE) properties, demonstrating the synthetic potential in drug discovery and material development.

Melatonin improves stroke by inhibiting autophagy-dependent ferroptosis mediated by NCOA4 binding to FTH1.

Ischemic stroke is a disease associated with high morbidity and disability rates; however, its pathogenesis remains elusive, and treatment options are limited. Ferroptosis, an iron-dependent form of cell death, represents a novel avenue for investigation. The objective of this study was to explore the role of melatonin in MCAO-induced ferroptosis and elucidate its underlying molecular mechanism. To simulate brain damage and neuronal injury caused by ischemic stroke, we established a mouse model of MCAO and an HT-22 cell model of OGD/R. The therapeutic efficacy of melatonin was assessed through measurements of infarct size, brain edema, and neurological scores. Additionally, qRT-PCR, WB analysis, and Co-IP assays were employed to investigate the impact of melatonin on ferroptosis markers such as NCOA4 and FTH1 expression levels. Confocal microscopy was utilized to confirm the colocalization between ferritin and lysosomes. Furthermore, we constructed a SIRT6 siRNA model to validate the regulatory effect exerted by SIRT6 on NCOA4 as well as their binding interaction. The present study provides initial evidence that melatonin possesses the ability to mitigate neuronal damage induced by MCAO and OGD/R. Assessment of markers for oxidative damage and ferroptosis revealed that melatonin effectively inhibits intracellular Fe2+ levels, thereby suppressing ferroptosis. Additionally, our findings demonstrate that melatonin modulates the interaction between FTH1 and NCOA4 via SIRT6, influencing ferritin autophagy without affecting cellular macroautophagy. These findings provide reliable data support for the promotion and application of melatonin in clinical practice.