Laser-induced plasma micromachining on surfaces parallel to the incident laser in different solutions.

Laser-induced plasma micromachining (LIPMM) is an advanced technology that utilizes the plasma generated from laser breakdown to remove material, thereby facilitating the fabrication of microstructures. This paper explores the use of LIPMM on 304 stainless steel surfaces parallel to the laser beam in different solutions, focusing on the impact of the liquid environment on the machining process. It presents a theoretical analysis of the material removal mechanisms unique to this orientation and experimentally investigates how water, a salt solution, and ethanol affect plasma shockwave characteristics. Notably, the plasma shockwave in the salt solution demonstrates the most significant peak pressure and energy, enhancing the micromachining efficiency. These findings suggest that varying the liquid environment can significantly influence LIPMM's effectiveness, offering potential improvements in precision and control. This study broadens the understanding of LIPMM applications, especially in orientations not commonly explored, and opens new possibilities for advanced micromachining techniques in various industrial applications.

Alteration in early resting­state functional MRI activity in comatose survivors of cardiac arrest: a prospective cohort study.

BACKGROUND: This study aimed to explore the characteristics of abnormal regional resting-state functional magnetic resonance imaging (rs-fMRI) activity in comatose patients in the early period after cardiac arrest (CA), and to investigate their relationships with neurological outcomes. We also explored the correlations between jugular venous oxygen saturation (SjvO2) and rs-fMRI activity in resuscitated comatose patients. We also examined the relationship between the amplitude of the N20-baseline and the rs-fMRI activity within the intracranial conduction pathway of somatosensory evoked potentials (SSEPs). METHODS: Between January 2021 and January 2024, eligible post-resuscitated patients were screened to undergo fMRI examination. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) of rs-fMRI blood oxygenation level-dependent (BOLD) signals were used to characterize regional neural activity. Neurological outcomes were evaluated using the Glasgow-Pittsburgh cerebral performance category (CPC) scale at 3 months after CA. RESULTS: In total, 20 healthy controls and 31 post-resuscitated patients were enrolled in this study. The rs-fMRI activity of resuscitated patients revealed complex changes, characterized by increased activity in some local brain regions and reduced activity in others compared to healthy controls (P < 0.05). However, the mean ALFF values of the whole brain were significantly greater in CA patients (P = 0.011). Among the clusters of abnormal rs-fMRI activity, the cluster values of ALFF in the left middle temporal gyrus and inferior temporal gyrus and the cluster values of ReHo in the right precentral gyrus, superior frontal gyrus and middle frontal gyrus were strongly correlated with the CPC score (P < 0.001). There was a strong correlation between the mean ALFF and SjvO2 in CA patients (r = 0.910, P < 0.001). The SSEP N20-baseline amplitudes in CA patients were negatively correlated with thalamic rs-fMRI activity (all P < 0.001). CONCLUSIONS: This study revealed that abnormal rs-fMRI BOLD signals in resuscitated patients showed complex changes, characterized by increased activity in some local brain regions and reduced activity in others. Abnormal BOLD signals were associated with neurological outcomes in resuscitated patients. The mean ALFF values of the whole brain were closely related to SjvO2 levels, and changes in the thalamic BOLD signals correlated with the N20-baseline amplitudes of SSEP responses. TRIAL REGISTRATION: NCT05966389 (Registered July 27, 2023).

MiR-342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb-susceptible mice and TB patients have relatively low miR-342-3p expression, while mice with miR-342-3p overexpression are more resistant to Mtb. We demonstrate that the miR-342-3p/SOCS6 axis regulates anti-Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR-342-3p/SOCS6 axis participates in the switching between Mtb-induced apoptosis and necrosis through A20-mediated K48-linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA-mRNA network and pave the way for host-directed therapies targeting these pathways.

Integrative analysis of HASMCs gene expression profile revealed the role of thrombin in the pathogenesis of atherosclerosis.

We explored the effect of thrombin on human aortic smooth muscle cells (HASMCs) and further analyzed its role in the pathogenesis of atherosclerosis (AS). Thrombin-induced differentially expressed genes (DEGs) in HASMCs were identified by analyzing expression profiles from the GEO. Subsequently, enrichment analysis, GSEA, PPI network, and gene-microRNAs networks were interrogated to identify hub genes and associated pathways. Enrichment analysis results indicated that thrombin causes HASMCs to secrete various pro-inflammatory cytokines and chemokines, exacerbating local inflammatory response in AS. Moreover, we identified 9 HUB genes in the PPI network, which are closely related to the inflammatory response and the promotion of the cell cycle. Additionally, we found that thrombin inhibits lipid metabolism and autophagy of HASMCs, potentially contributing to smooth muscle-derived foam cell formation. Our study deepens a mechanistic understanding of the effect of thrombin on HASMCs and provides new insight into treating AS.

Effects of Traditional Chinese Medicine Five-Element Music Therapy Combined with Mirtazapine on Depression and Limb Function Recovery After Ischemic Stroke.

Objective: To observe the effects of traditional Chinese medicine (TCM) five-element music therapy combined with mirtazapine on depression and limb function recovery after ischemic stroke. Methods: A total of 110 patients treated in the Departments of Geriatrics, Cardiology, and Psychology of three hospitals in Qinhuangdao City, Hebei Province, China from October 2022 to August 2023 were selected. Based on the scores of 24-item Hamilton Depression Scale (HAMD-24), Barthel (BL) index, and National Institute of Health Stroke Scale (NIHSS) before enrollment, the patients were randomly divided into control group (n = 58) and experimental group (n = 52). The patients in control group were treated with limb rehabilitation, while those in experimental group underwent limb rehabilitation combined with five-element music therapy and mirtazapine. Results: After 12 weeks of treatment and observation, 11 patients in control group and 9 patients in experimental group withdrew from this trail. As for the proportions of score changes, experimental group had higher decline proportions of HAMD-24 score and NIHSS score as well as an increased proportion of BL index score than control group, which were 43.97%, 69.32%, and 44.12%, respectively. Conclusion: TCM five-element music therapy combined with mirtazapine significantly improves depression and limb function recovery after ischemic stroke.

Pain catastrophizing and associated factors in preoperative total knee arthroplasty in Lanzhou, China: a cross-sectional study.

BACKGROUND: Pain catastrophizing in preoperative total knee arthroplasty (TKA) patients is associated with several poorly characterised factors in the literature. This study investigated the current state and associated factors of preoperative pain catastrophizing in patients undergoing TKA. METHODS: This descriptive cross-sectional study was conducted at the orthopedics ward of two tertiary hospitals in Lanzhou, China. Pain catastrophizing was measured using the Chinese versions of the Pain Catastrophizing Scale, Short Form-36 (physical function domain), Numerical Rating Scale, Oxford Knee Score, Hospital Anxiety and Depression Scale, and Life Orientation Test-Revised. RESULTS: The study included 360 participants. Preoperative TKA pain catastrophizing in all patients was high, with a mean score of 24.92 (SD: 12.38). The stepwise multiple linear regression analysis revealed anxiety (ß = 0.548, P < 0.01), education level (ß = - 0.179, P < 0.01), physical function (ß = - 0.156, P < 0.01), and pain intensity during activity (ß = 0.105, P = 0.015) as associated factors for pain catastrophizing, possibly explaining 51.2% of the total variation (F = 95.149, P < 0.01). CONCLUSION: Anxiety was the most relevant factor for pain catastrophizing in patients with preoperative TKA. Lower education levels, poor physical function, and stronger pain intensity during the activity were also associated with pain catastrophizing.

Wettability Transition of the Picosecond Laser-Ablated 304 Stainless-Steel Surface via Low-Vacuum Heat Treatment.

Inspired by natural creatures, superhydrophobic surfaces with various adhesion behaviors have attracted significant scientific interest. In this study, by controlling the laser fluence, the scanning times, and the subsequent cleaning method, microcolumn arrays with different morphologies were fabricated on 304 stainless-steel surfaces using picosecond laser direct writing. To achieve wettability transition, the laser-processed samples were then subjected to heat treatments (120 °C) in air and in a low vacuum environment (6 kPa). The results show that after heat treatment in different environments and with various time lengths, the laser-processed surfaces become hydrophobic surfaces with different adhesion properties. It is worth noting that while surfaces heat-treated in air exhibit weak wettability transition potential and high adhesion, the surfaces heat-treated in a low vacuum environment present superhydrophobic and low adhesion properties with a minimum sliding angle of about 3.14°. Moreover, the low-vacuum heat-treated surfaces retain good superhydrophobic properties after 1 month of observation as well as an abrasion test. These transitions in hydrophobic behavior and adhesion properties may be mainly attributed to the heat treatment-induced (in the air or in a low vacuum environment) redistribution of surface compounds and the microstructure-induced alternation of the solid-liquid contact state. By controlling the laser processing parameters and the heat treatment time and environment, stable wettability transition and flexible adhesion control of stainless steel can be easily achieved.

Fabrication of ordered hierarchical structures on stainless steel by picosecond laser for modified wettability applications.

Ordered hierarchical structures were fabricated on a stainless steel surface using a single picosecond laser for highly controllable dimensions. Picosecond laser induced periodic structures were firstly used to create large-scale nano-structures with a period of ~450 nm. Subsequently, laser direct writing, by simply changing process parameters was employed to create micro squared structures with 19 µm width, 19 µm interval and 3-7.5 µm depth on the previously created nano-structures. As a result, micro squared structures covered by uniform nano-structures, similar to examples present in nature, were successfully fabricated. Additionally, the wettability of the created hierarchical structures was analyzed. The results demonstrated that the combination of both micro- and nano-structures allowed to tune the wetting behavior, presenting a great potential for wettability applications.

Formation of laser induced periodic structures on stainless steel using multi-burst picosecond pulses.

The formation of periodic structures on stainless steel under linearly polarized multi-burst picosecond laser pulses irradiation was experimentally investigated. The resulting structures were characterized by scanning electron microscopy (SEM) analysis. This analysis of images revealed four distinctive (quasi-) periodic structures depending on the laser irradiation parameters, i.e., LSFLs, HSFLs, micro-grooves and nano-holes. It is demonstrated that the multi-burst picosecond pulses technique is capable of fabricating periodic structures with different scales and shapes.

Structural basis for the geometry-driven localization of a small protein.

In bacteria, certain shape-sensing proteins localize to differently curved membranes. During sporulation in Bacillus subtilis, the only convex (positively curved) surface in the cell is the forespore, an approximately spherical internal organelle. Previously, we demonstrated that SpoVM localizes to the forespore by preferentially adsorbing onto slightly convex membranes. Here, we used NMR and molecular dynamics simulations of SpoVM and a localization mutant (SpoVM(P9A)) to reveal that SpoVM's atypical amphipathic α-helix inserts deeply into the membrane and interacts extensively with acyl chains to sense packing differences in differently curved membranes. Based on binding to spherical supported lipid bilayers and Monte Carlo simulations, we hypothesize that SpoVM's membrane insertion, along with potential cooperative interactions with other SpoVM molecules in the lipid bilayer, drives its preferential localization onto slightly convex membranes. Such a mechanism, which is distinct from that used by high curvature-sensing proteins, may be widely conserved for the localization of proteins onto the surface of cellular organelles.

A membrane proximal helix in the cytosolic domain of the human APP interacting protein LR11/SorLA deforms liposomes.

Over the last decade, compelling evidence has linked the development of Alzheimer's disease (AD) to defective intracellular trafficking of the amyloid precursor protein (APP). Faulty APP trafficking results in an overproduction of Aß peptides, which is generally agreed to be the primary cause of AD-related pathogenesis. LR11 (SorLA), a type I transmembrane sorting receptor, has emerged as a key regulator of APP trafficking and processing. It directly interacts with APP and diverts it away from amyloidogenic processing. The 54-residue cytosolic domain of LR11 is essential for its proper intracellular localization and trafficking which, in turn, determines the fate of APP. Here, we have found a surprising membrane-proximal amphipathic helix in the cytosolic domain of LR11. Moreover, a peptide corresponding to this region folds into an α-helical structure in the presence of liposomes and transforms liposomes to small vesicles and tubule-like particles. We postulate that this amphipathic helix may contribute to the dynamic remodeling of membrane structure and facilitate LR11 intracellular transport.

Proteomics-based screening of AKR1B1 as a therapeutic target and validation study for sepsis-associated acute kidney injury.

Background: Sepsis and sepsis-associated acute kidney injury (SA-AKI) pose significant global health challenges, necessitating the development of innovative therapeutic strategies. Dysregulated protein expression has been implicated in the initiation and progression of sepsis and SA-AKI. Identifying potential protein targets and modulating their expression is crucial for exploring alternative therapies. Method: We established an SA-AKI rat model using cecum ligation perforation (CLP) and employed differential proteomic techniques to identify protein expression variations in kidney tissues. Aldose reductase (AKR1B1) emerged as a promising target. The SA-AKI rat model received treatment with the aldose reductase inhibitor (ARI), epalrestat. Blood urea nitrogen (BUN) and creatinine (CRE) levels, as well as IL-1ß, IL-6 and TNF-α levels in the serum and kidney tissues, were monitored. Hematoxylin-eosin (H-E) staining and a pathological damage scoring scale assessed renal tissue damage, while protein blotting determined PKC (protein kinase C)/NF-κB pathway protein expression. Result: Differential proteomics revealed significant downregulation of seven proteins and upregulation of 17 proteins in the SA-AKI rat model renal tissues. AKR1B1 protein expression was notably elevated, confirmed by Western blot. ARI prophylactic administration and ARI treatment groups exhibited reduced renal injury, low BUN and CRE levels and decreased IL-1ß, IL-6 and TNF-α levels compared to the CLP group. These changes were statistically significant (P < 0.05). AKR1B1, PKC-α, and NF-κB protein expression levels were also lowered in the ARI prophylactic administration and ARI treatment groups compared to the CLP group (P < 0.05). Conclusions: Epalrestat appeared to inhibit the PKC/NF-κB inflammatory pathway by inhibiting AKR1B1, resulting in reduced inflammatory cytokine levels in renal tissues and blood. This mitigated renal tissue injuries and improved the systemic inflammatory response in the severe sepsis rat model. Consequently, AKR1B1 holds promise as a target for treating sepsis-associated acute kidney injuries.

Baicalin attenuates acute skin damage induced by ultraviolet B via inhibiting pyroptosis.

As the outermost layer of the human body, the skin suffers from various external factors especially light damage, among which ultraviolet B (UVB) irradiation is common and possesses a relatively high biological damage capacity. Pyroptosis is a newly discovered type of programmed cell death, which can induce cell rupture and induce local inflammatory response. However, the molecular mechanisms of pyroptosis in photodamaged skin is poorly understood. Baicalin, a flavonoid extracted from the desiccated root of Scutellaria baicalensis Georgi (Huang Qin). Despite its antioxidant abilities, whether baicalin protects skin by attenuating UVB-induced pyroptosis remains unclear, which was the aim of this study. The UVB-induced acute skin damage model was established by using human immortalized keratinocytes (HaCaT cells) and Kunming (KM) strain mice. The protective dose selection for baicalin is 50 µM in vitro and 100 mg/kg in vivo. In in vitro study, UVB irradiation significantly decreased cell viability, increased cell death and oxidative stress in HaCaT cells, while pretreatment with baicalin improved these phenomena. Furthermore, the baicalin pretreatment notably suppressed nuclear factor kappa B (NF-κB) translocation, the NLRP3 inflammasome activation and gasdermin D (GSDMD) maturation, thus effectively attenuating UVB-induced pyroptosis. In in vivo study, the baicalin pretreatment mitigated epidermal hyperplasia, collagen fiber fragmentation, oxidative stress and pyroptosis in UVB-irradiated mouse skin. In a nutshell, this study suggests that baicalin could be a potential protective agent to attenuate acute skin damage induced by UVB irradiation through decreasing oxidative stress and suppressing NF-κB/NLRP3/GSDMD-involved pyroptosis.

Kinetic isotope effects support the twisted amide mechanism of Pin1 peptidyl-prolyl isomerase.

The Pin1 peptidyl-prolyl isomerase catalyzes isomerization of pSer/pThr-Pro motifs in regulating the cell cycle. Peptide substrates, Ac-Phe-Phe-phosphoSer-Pro-Arg-p-nitroaniline, were synthesized in unlabeled form, and with deuterium-labeled Ser-d3 and Pro-d7 amino acids. Kinetic data were collected as a function of Pin1 concentration to measure kinetic isotope effects (KIEs) on catalytic efficiency (kcat/Km). The normal secondary (2°) KIE value measured for the Ser-d3 substrate (kH/kD = 1.6 ± 0.2) indicates that the serine carbonyl does not rehybridize from sp(2) to sp(3) in the rate-determining step, ruling out a nucleophilic addition mechanism. The normal 2° KIE can be explained by hyperconjugation between Ser α-C-H/D and C═O and release of steric strain upon rotation of the amide bond from cis to syn-exo. The inverse 2° KIE value (kH/kD = 0.86 ± 0.08) measured for the Pro-d7 substrate indicates rehybridization of the prolyl nitrogen from sp(2) to sp(3) during the rate-limiting step of isomerization. No solvent kinetic isotope was measured by NMR exchange spectroscopy (kH2O/kD2O = 0.92 ± 0.12), indicating little or no involvement of exchangeable protons in the mechanism. These results support the formation of a simple twisted amide transition state as the mechanism for peptidyl prolyl isomerization catalyzed by Pin1. A model of the reaction mechanism is presented using crystal structures of Pin1 with ground state analogues and an inhibitor that resembles a twisted amide transition state.

Sensitive nanochannel biosensor for T4 polynucleotide kinase activity and inhibition detection.

5'-Polynucleotide kinase is a crucial class of enzyme that catalyzes the phosphorylation of nucleic acids with 5'-hydroxyl termini. This process regulates many important cellular events, especially DNA repair during strand damage and interruption. The activity and inhibition of nucleotide kinase have proven to be an evident effect on cellular nucleic acid regulation and metabolism. Here, we describe a novel nanochannel biosensor for monitoring the activity and inhibition of T4 polynucleotide kinase (PNK), a famous member of the 5'-kinase family playing a major role in the cellular responses to DNA damage. On the basis of the functionalized nanochannel system and coupled λ exonuclease cleavage reaction, the nanochannel-sensing platform exhibits high sensitivity and convenience toward kinase analysis. Biotin-labeled dsDNA effectively blocks the streptavidin-modified nanochannel through forming a closely packed arrangement of DNA structure inside the channel. When dsDNA is phosphorylated by PNK and then immediately cleaved by λ exonuclease, the pore-blocking effect almost disappears. This PNK-induced microstructural distinctness can be directly and accurately monitored by the nanochannel system, which benefits from its high sensitivity to the change of the effective pore size. Furthermore, modification convenience and mechanical robustness also ensure the stability of the test platform. This as-proposed strategy exhibits excellent analytical performance in both PNK activity analysis and inhibition evaluation. The simple and sensitive nanochannel biosensor shows great potential in developing on-chip, high-throughput assays for fundamental biochemical process research, molecular-target therapies, and clinic diagnostics.

Tofacitinib reduces acute lung injury and improves survival in a rat model of sepsis by inhibiting the JAK-STAT/NF-κB pathway.

Acute lung injury is a major cause of death in sepsis. Tofacitinib (TOFA), a JAK inhibitor, has anti-inflammatory activity in autoimmune diseases, but its role in acute lung injury in sepsis remains unclear. The purpose of this study is to establish a septic rat model by cecal ligation and perforation, and to evaluate the effect of tofacitinib on the survival rate of septic rat model and its role in acute lung injury in septic rats and the possible mechanism of action. In this study, TOFA (1 mg/kg, 3 mg/kg, 10 mg/kg) was used to observe the survival rate of septic rats. It was found that TOFA (10 mg/kg) significantly improved the survival rate of septic rats. We selected TOFA (10 mg/kg) and focused on the protective effect of TOFA on acute lung injury. The results confirmed that TOFA significantly inhibited the expression of TNF-α, IL-1ß, IL-6 and IFN-γ inflammatory factors, reduced the W/D weight ratio of septic lung tissue, and significantly improved lung histopathological damage. These results may be related to the inhibitory effect of TOFA on JAK-STAT/NF-κ B signaling pathway. In conclusion, for the first time, we found that TOFA has a protective effect against sepsis-induced acute lung injury, and it may be a promising drug for the treatment of acute lung injury in sepsis.

Protective effect of basic helix-loop-helix family member e40 on cerebral ischemia/reperfusion injury: Inhibition of apoptosis via repressing the transcription of pleckstrin homology-like domain family A, member 1.

BACKGROUND: During ischemic stroke treatment, cerebral ischemia/reperfusion (I/R) injury results in neuronal cell death and neurological dysfunctions in brain. Previous studies indicate that basic helix-loop-helix family member e40 (BHLHE40) exerts protective effects on the pathology of neurogenic diseases. However, the protective function of BHLHE40 in I/R is unclear. OBJECTIVES: This study aimed to explore the expression, role and potential mechanism of BHLHE40 after ischemia. MATERIAL AND METHODS: We established models of I/R injury in rats and of oxygen-glucose deprivation/reoxygenation (OGD/R) in primary hippocampal neurons. Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to detect neuronal injury and apoptosis. Immunofluorescence was used to detect BHLHE40 expression. Cell viability and cell damage measurements were conducted using Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) assay. The regulation of BHLHE40 to pleckstrin homology-like domain family A, member 1 (PHLDA1) was assessed using the dual-luciferase assay and chromatin immunoprecipitation (ChIP) assay. RESULTS: Cerebral I/R rats exhibited severe neuronal loss and apoptosis in hippocampal cornu Ammonis 1 (CA1) region, accompanied by downregulated BHLHE40 expression at both mRNA and protein levels, indicating that BHLHE40 may regulate the apoptosis of hippocampal neurons. The function of BHLHE40 in neuronal apoptosis during cerebral I/R was further explored by establishing an OGD/R model in vitro. Low expression of BHLHE40 was also observed in neurons treated with OGD/R. The OGD/R administration inhibited cell viability and enhanced cell apoptosis in hippocampal neurons, whereas BHLHE40 overexpression reversed those changes. Mechanistically, we demonstrated that BHLHE40 could repress PHLDA1 transcription by binding to PHLDA1 promoter. The PHLDA1 is a facilitator of neuronal damage in brain I/R injury and its upregulation reversed the effects caused by BHLHE40 overexpression in vitro. CONCLUSIONS: The transcription factor BHLHE40 may protect against brain I/R injury through repressing cell damage via regulating PHLDA1 transcription. Thus, BHLHE40 may be a candidate gene for further study of molecular or therapeutic targets for I/R.

Prediction and identification of potential immunodominant epitopes in glycoproteins B, C, E, G, and I of herpes simplex virus type 2.

Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2(466-473) (EQDRKPRN), gC2(216-223) (GRTDRPSA), gE2(483-491) (DPPERPDSP), gG2(572-579) (EPPDDDDS), and gI2(286-295) (CRRRYRRPRG) had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2.

Protective effect of Secukinumab on severe sepsis model rats by neutralizing IL-17A to inhibit IKBα/NFκB inflammatory signal pathway.

Secukinumab is a specific neutralizing antibody for IL-17A. At present, numerous studies have confirmed the important role of IL-17A in sepsis, but the role of secukinumab in sepsis has not been studied. The present study explored the protective effect and underlying mechanism of secukinumab in severe sepsis model rats. We established a severe sepsis rat model using cecal ligation and puncture (CLP). The optimal dose of secukinumab was determined by observing the 7-day survival rate of severe sepsis model rats. The expression levels of TNF-α, IL-6, and IL-17A in plasma and lung tissue were determined by enzyme-linked immunosorbent assay. The degree of pathological damage to lung tissue was evaluated by hematoxylin-eosin (H-E) staining and pathological damage scale. The expressions of IKBα/NFκB pathway proteins and downstream-related inflammatory factors were detected by western blotting and real-time quantitative polymerase chain reaction (RT-qPCR). Our results show that high-dose secukinumab can inhibit the activation of the IKBα/NFκB inflammatory pathway by neutralizing IL-17A and reducing the gene expression of pathway-related inflammatory cytokines, thereby reducing the levels of inflammatory cytokines in lung tissue and plasma, thereby reducing the damage of lung tissue in severe sepsis model rats and improving the systemic inflammatory response.

Reconfigurable and Efficient Implementation of 16 Boolean Logics and Full-Adder Functions with Memristor Crossbar for Beyond von Neumann In-Memory Computing.

The rise of emerging technologies such as Big Data, the Internet of Things, and artificial intelligence, which requires efficient power schemes, is driving brainstorming in data computing and storage technologies. In this study, merely relying on the fundamental structure of two memristors and a resistor, arbitrary Boolean logic can be reconfigured and calculated in two steps, while no additional voltage sources are needed beyond "±VP " and 0, and all state reversals are based on memristor set switching. Utilizing the proposed logic scheme in an elegant form of unity structure and minimum cost, the implementation of a 1-bit adder is demonstrated economically, and a promising circuit scheme for the N-bit adder is exhibited. Some critical issues including the crosstalk problem, energy consumption, and peripheral circuits are further simulated and discussed. Compared with existing works on memristive logic, such methods support building a memristor-based digital in-memory calculation system with high functional reconfigurability, simple voltage sources, and low power and area consumption.