HuoXueTongFu formula induces M2c macrophages via the MerTK/PI3K/AKT pathway to eliminate NETs in intraperitoneal adhesion in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: HuoXueTongFu Formula (HXTF) is a traditional Chinese herbal formula that has been used as a supplement and alternative therapy for intraperitoneal adhesion (IA). However, its specific mechanism of action has not been fully understood. AIM OF THE STUDY: In surgery, IA presents an inevitable challenge, significantly impacting patients' physical and mental well-being and increasing the financial burden. Our previous research has confirmed the preventive effects of HXTF on IA formation. However, the precise mechanism of its action still needs to be understood. METHODS: In this study, the IA model was successfully established by using the Ischemic buttons and treated with HXTF for one week with or without Mer Tyrosine Kinase (MerTK) inhibitor. We evaluated the pharmacodynamic effect of HXTF on IA mice. The MerTK/phosphoinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway-associated proteins were detected by Western blotting. Neutrophil extracellular traps (NETs) were detected by immunofluorescence. Macrophage phenotype was assessed by immunohistochemistry and flow cytometry. Inflammatory cytokines were detected by Real Time Quantitative PCR and Western blotting. RESULTS: HXTF reduced inflammatory response and alleviated IA. HXTF significantly enhanced MerTK expression, increased the number of M2c macrophages, and decreased the formation of NETs. In addition, the MerTK/PI3K/AKT pathway was significantly activated by HXTF. However, after using MerTK inhibitors, the role of HXTF in inducing M2c macrophage through activation of the PI3K/AKT pathway was suppressed and there was no inhibitory effect on NETs formation and inflammatory responses, resulting in diminished inhibition of adhesion. CONCLUSION: HXTF may improve IA by activating the MerTK/PI3K/AKT pathway to induce M2c polarization, which removes excess NETs and attenuates the inflammatory response.

Emerging roles of lactate in acute and chronic inflammation.

Traditionally, lactate has been considered a 'waste product' of cellular metabolism. Recent findings have shown that lactate is a substance that plays an indispensable role in various physiological cellular functions and contributes to energy metabolism and signal transduction during immune and inflammatory responses. The discovery of lactylation further revealed the role of lactate in regulating inflammatory processes. In this review, we comprehensively summarize the paradoxical characteristics of lactate metabolism in the inflammatory microenvironment and highlight the pivotal roles of lactate homeostasis, the lactate shuttle, and lactylation ('lactate clock') in acute and chronic inflammatory responses from a molecular perspective. We especially focused on lactate and lactate receptors with either proinflammatory or anti-inflammatory effects on complex molecular biological signalling pathways and investigated the dynamic changes in inflammatory immune cells in the lactate-related inflammatory microenvironment. Moreover, we reviewed progress on the use of lactate as a therapeutic target for regulating the inflammatory response, which may provide a new perspective for treating inflammation-related diseases.

Enhanced Selective Electrosorption of Nitrate from Wastewater by Controllably Doping Nitrogen into Porous Carbon with Micropores.

The biological NO3- removal process might be accompanied by high CO2 emissions and operation costs. Capacitive deionization (CDI) has been widely studied as a very efficient method to purify water. Here, a porous carbon material with a tunable nitrogen configuration was developed. Characterization and density functional theory calculation show that nitrogenous functional groups have a higher NO3- binding energy than Cl-, SO42-, and H2PO4-. In addition, the selectivity of NO3- is improved after the introduction of micropores by using the pore template. The NO3- ion removal and selectivity of MN-C-12 are 4.57 and 3.46-5.42 times that of activated carbon (AC), respectively. The high NO3- selectivity and electrosorption properties of MN-C-12 (the highest N content and micropore area) are due to the synergistic effect of the affinity of nitrogen functional groups to NO3- and microporous ion screening. A CDI unit for the removal of nitrogen from municipal wastewater was constructed and applied to treat wastewater meeting higher discharge standards of A (N: 15 mg L-1) and B (N: 20 mg L-1) ((GB18918-2002), China). This work provides new insights into enhanced carbon materials for the selective electrosorption of wastewater by CDI technology.

Anion-Counterion Strategy toward Organic Cocrystal Engineering for Near-Infrared Photothermal Conversion and Solar-Driven Water Evaporation.

An anion-counterion strategy is proposed to construct organic mono-radical charge-transfer cocrystals for near-infrared photothermal conversion and solar-driven water evaporation. Ionic compounds with halogen anions as the counterions serve as electron donors, providing the necessary electrons for efficient charge transfer with unchanged skeleton atoms and structures as well as the broad red-shifted absorption (200-2000 nm) and unprecedented photothermal conversion efficiency (~90.5 %@808 nm) for the cocrystals. Based on these cocrystals, an excellent solar-driven interfacial water evaporation rate up to 6.1±1.1 kg ⋅ m-2 ⋅ h-1 under 1 sun is recorded due to the comprehensive evaporation effect from the cocrystal loading in polyurethane foams and chimney addition, such performance is superior to the reported results on charge-transfer cocrystals or other materials for solar-driven interfacial evaporation. This prototype exhibits the great potential of cocrystals prepared by the one-step mechanochemistry method in practical large-scale seawater desalination applications.

Research Progress in the Mechanisms of Resistance to Biotic Stress in Sweet Potato.

Sweet potato (Ipomoea batatas (L.) Lam.) is one of the most important food, feed, industrial raw materials, and new energy crops, and is widely cultivated around the world. China is the largest sweet potato producer in the world, and the sweet potato industry plays an important role in China's agriculture. During the growth of sweet potato, it is often affected by biotic stresses, such as fungi, nematodes, insects, viruses, and bacteria. These stressors are widespread worldwide and have severely restricted the production of sweet potato. In recent years, with the rapid development and maturity of biotechnology, an increasing number of stress-related genes have been introduced into sweet potato, which improves its quality and resistance of sweet potato. This paper summarizes the discovery of biological stress-related genes in sweet potato and the related mechanisms of stress resistance from the perspectives of genomics analysis, transcriptomics analysis, genetic engineering, and physiological and biochemical indicators. The mechanisms of stress resistance provide a reference for analyzing the molecular breeding of disease resistance mechanisms and biotic stress resistance in sweet potato.

SpikingJelly: An open-source machine learning infrastructure platform for spike-based intelligence.

Spiking neural networks (SNNs) aim to realize brain-inspired intelligence on neuromorphic chips with high energy efficiency by introducing neural dynamics and spike properties. As the emerging spiking deep learning paradigm attracts increasing interest, traditional programming frameworks cannot meet the demands of the automatic differentiation, parallel computation acceleration, and high integration of processing neuromorphic datasets and deployment. In this work, we present the SpikingJelly framework to address the aforementioned dilemma. We contribute a full-stack toolkit for preprocessing neuromorphic datasets, building deep SNNs, optimizing their parameters, and deploying SNNs on neuromorphic chips. Compared to existing methods, the training of deep SNNs can be accelerated 11×, and the superior extensibility and flexibility of SpikingJelly enable users to accelerate custom models at low costs through multilevel inheritance and semiautomatic code generation. SpikingJelly paves the way for synthesizing truly energy-efficient SNN-based machine intelligence systems, which will enrich the ecology of neuromorphic computing.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Sweet potato NAC transcription factor NAC43 negatively regulates plant growth by causing leaf curling and reducing photosynthetic efficiency.

Leaves comprise one of the most important organs for plant growth and development. Although there have been some reports on leaf development and the establishment of leaf polarity, their regulatory mechanisms are not very clear. In this study, we isolated a NAC (NAM, ATAF, and CUC) transcription factor (TF), i.e., IbNAC43, from Ipomoea trifida, which is a wild ancestor of sweet potato. This TF was highly expressed in the leaves and encoded a nuclear localization protein. The overexpression of IbNAC43 caused leaf curling and inhibited the growth and development of transgenic sweet potato plants. The chlorophyll content and photosynthetic rate in transgenic sweet potato plants were significantly lower than those in wild-type (WT) plants. Scanning electron microscopy (SEM) and paraffin sections showed that the ratio of cells in the upper and lower epidermis of the transgenic plant leaves was unbalanced; moreover, the abaxial epidermal cells were irregular and uneven in transgenic plants. In addition, the xylem of transgenic plants was more developed than that of WT plants, while their lignin and cellulose contents were significantly higher than those of WT. Quantitative real-time PCR (qRT-PCR) analysis showed that the overexpression of IbNAC43 upregulated the genes involved in leaf polarity development and lignin biosynthesis in transgenic plants. Moreover, it was found that IbNAC43 could directly activate the expression of the leaf adaxial polarity-related genes IbREV and IbAS1 by binding to their promoters. These results indicate that IbNAC43 might play a critical role in plant growth by affecting the establishment of leaf adaxial polarity. This study provides new insights regarding leaf development.

Genome-Wide Characterization of the PIFs Family in Sweet Potato and Functional Identification of IbPIF3.1 under Drought and Fusarium Wilt Stresses.

Phytochrome-interacting factors (PIFs) are essential for plant growth, development, and defense responses. However, research on the PIFs in sweet potato has been insufficient to date. In this study, we identified PIF genes in the cultivated hexaploid sweet potato (Ipomoea batatas) and its two wild relatives, Ipomoea triloba, and Ipomoea trifida. Phylogenetic analysis revealed that IbPIFs could be divided into four groups, showing the closest relationship with tomato and potato. Subsequently, the PIFs protein properties, chromosome location, gene structure, and protein interaction network were systematically analyzed. RNA-Seq and qRT-PCR analyses showed that IbPIFs were mainly expressed in stem, as well as had different gene expression patterns in response to various stresses. Among them, the expression of IbPIF3.1 was strongly induced by salt, drought, H2O2, cold, heat, Fusarium oxysporum f. sp. batatas (Fob), and stem nematodes, indicating that IbPIF3.1 might play an important role in response to abiotic and biotic stresses in sweet potato. Further research revealed that overexpression of IbPIF3.1 significantly enhanced drought and Fusarium wilt tolerance in transgenic tobacco plants. This study provides new insights for understanding PIF-mediated stress responses and lays a foundation for future investigation of sweet potato PIFs.

Remodeling of the osteoimmune microenvironment after biomaterials implantation in murine tibia: Single-cell transcriptome analysis.

Osseointegration seems to be a foreign body reaction equilibrium due to the complicated interactions between the immune and skeletal systems. The heterogeneity of the osteoimmune microenvironment in the osseointegration of implant materials remains elusive. Here, a single-cell study involving 40043 cells is conducted, and a total of 10 distinct cell clusters are identified from five different groups. A preliminary description of the osteoimmune microenvironment revealed the diverse cellular heterogeneity and dynamic changes modulated by implant properties. The increased immature neutrophils, Ly6C + CCR2hi monocytes, and S100a8hi macrophages induce an aggressive inflammatory response and eventually lead to the formation of fibrous capsule around the stainless steel implant. The enrichment of mature neutrophils, FcgR1hi and differentiated immunomodulatory macrophages around the titanium implant indicates favorable osseointegration under moderate immune response. Neutrophil-depletion mice are conducted to explore the role of neutrophils in osseointegration. Neutrophils may improve bone formation by enhancing the recruitment of BMSCs via the CXCL12/CXCR3 signal axis. These findings contribute to a better knowledge of osteoimmunology and are valuable for the design and modification of 'osteoimmune-smart' biomaterials in the bone regeneration field.

Snapshot multi-frame parallel spectral holographic microscopy based on a reconfigurable optical comb.

We present a snapshot multi-frame parallel holographic microscopy system through a reconfigurable optical comb source, which consists of a digital micromirror device (DMD) based spectrum filter system and a spectroscopic Michelson interferometric system. The proposed system allows arbitrarily tuning comb spacing and comb number, and the capturing of multi-frame images without overlap in one exposure. As a result, high-quality spectral holograms can be obtained with less acquisition time. The performance of the system is detailed in the experiment and 45-wavelengths holographic imaging for perovskite micro-platelets is conducted, which proves the system has the ability to realize high-performance four-dimensional (4D) imaging.

The role of dendritic cells in the immunomodulation to implanted biomaterials.

Considering the substantial role played by dendritic cells (DCs) in the immune system to bridge innate and adaptive immunity, studies on DC-mediated immunity toward biomaterials principally center on their adjuvant effects in facilitating the adaptive immunity of codelivered antigens. However, the effect of the intrinsic properties of biomaterials on dendritic cells has not been clarified. Recently, researchers have begun to investigate and found that biomaterials that are nonadjuvant could also regulate the immune function of DCs and thus affect subsequent tissue regeneration. In the case of proteins adsorbed onto biomaterial surfaces, their intrinsic properties can direct their orientation and conformation, forming "biomaterial-associated molecular patterns (BAMPs)". Thus, in this review, we focused on the intrinsic physiochemical properties of biomaterials in the absence of antigens that affect DC immune function and summarized the underlying signaling pathways. Moreover, we preliminarily clarified the specific composition of BAMPs and the interplay between some key molecules and DCs, such as heat shock proteins (HSPs) and high mobility group box 1 (HMGB1). This review provides a new direction for future biomaterial design, through which modulation of host immune responses is applicable to tissue engineering and immunotherapy.

The Characteristics of Microbiome and Cytokines in Healthy Implants and Peri-Implantitis of the Same Individuals.

AIM: To characterize the profile of submucosal microbiome and cytokine levels in peri-implant crevicular fluid (PICF) from clinically healthy implants and peri-implantitis in the same individuals. MATERIAL AND METHODS: A total of 170 patients were screened and, finally, 14 patients with at least one healthy implant and one peri-implantitis implant were included. Submucosal microbiota and cytokines from 28 implants were analyzed using 16S rRNA gene sequencing and multifactor assays, respectively. Correlations of clinical indexes and microbiota or cytokines were analyzed using Spearman's correlation coefficient. A random forest classification model was constructed. RESULTS: Peri-implantitis sites harbored higher microbial diversity, as well as more Gram-negative bacteria and anaerobic bacteria, compared with healthy implants sites. The genera of Peptostreptococcaceae XIG-1, Treponema, Porphyromonas, and Lachnospiraceae G-8, as well as the cytokines of IL-17A, IL-6, IL-15, G-CSF, RANTES, and IL-1ß were significantly higher in peri-implantitis than healthy implants. Furthermore, these genera and cytokines had positive relationships with clinical parameters, including probing depth (PD), bleeding on probing (BOP), and marginal bone loss (MBL). The classification model picked out the top 15 biomarkers, such as IL-17A, IL-6, IL-15, VEGF, IL-1ß, Peptostreptococcaceae XIG-1, Haemophilus, and Treponema, and obtained an area under the curve (AUC) of 0.85. CONCLUSIONS: There are more pathogenic bacteria and inflammatory cytokines in peri-implantitis sites, and biomarkers could facilitate the diagnosis of peri-implantitis.

A Novel Prognostic Ferroptosis-Related lncRNA Signature Associated with Immune Landscape in Invasive Breast Cancer.

Breast cancer (BC) represents the most common form of malignant tumors in women. However, the effectiveness of BC immunotherapy remains very low. Ferroptosis is a recently described form of programmed cell death which has unique characteristics, and associated long-chain noncoding RNAs (lncRNA) are thought to influence the occurrence and development of a variety of tumors. We identified 1,636 lncRNAs associated with ferroptosis in BC patients. 299 differentially expressed ferroptosis-related lncRNAs were subjected to univariate, LASSO regression, and multivariate Cox regression analyses to construct a ten ferroptosis-related lncRNA signature. This ten ferroptosis-related lncRNA signature performed very well in predicting survival of BC patients, and the risk score of the mRNA signature was identified as an independent prognostic factor in this cancer entity. In addition, the signature could be used to predict the immune landscape of BC patients. Low-risk patients had enriched immune-related pathways and more infiltration of most types of immune cells. The signature was also associated with the tumor mutation burden in BC. The results have allowed us to assess the potential for immunotherapy targets exposed by this model. The ferroptosis-related lncRNA risk model reported in the current study has clinical utility in BC prognosis and predicted immunotherapy response.

Improved osseointegration of strontium-modified titanium implants by regulating angiogenesis and macrophage polarization.

Strontium (Sr) has shown strong osteogenic potential and thereby been widely incorporated into dental and orthopedic implants. However, the improved osseointegration of strontium-modified titanium implants through regulation of angiogenesis and macrophage polarization is still beginning to be explored. Here, we demonstrated that the angiogenic capacity of human umbilical vein endothelial cells on the Sr-incorporated micro/nano titanium (SLA-Sr) surface was also significantly improved through the up-regulated expression of the HIF-1α protein and Erk1/2 phosphorylation. Meanwhile, SLA-Sr not only switched macrophage polarization towards the M2 phenotype, but also expressed a high level of pro-angiogenic platelet-derived growth factor. Furthermore, macrophage secretion induced by SLA-Sr was also capable of enhancing angiogenesis of human umbilical vein endothelial cells. In vivo experimental results also showed early vascularized implant osseointegration of SLA-Sr with the type H vessel formation around the SLA-Sr implant. This study emphasized the synergistic role of Sr in the regulation of macrophage polarization and angiogenesis, and therefore depicted the therapeutic potential of SLA-Sr for rapidly vascularized osseointegration.

Elucidating the Novel Mechanism of Ligustrazine in Preventing Postoperative Peritoneal Adhesion Formation.

Postoperative peritoneal adhesion (PPA) is a major clinical complication after open surgery or laparoscopic procedure. Ligustrazine is the active ingredient extracted from the natural herb Ligusticum chuanxiong Hort, which has promising antiadhesion properties. This study is aimed at revealing the underlying mechanisms of ligustrazine in preventing PPA at molecular and cellular levels. Both rat primary peritoneal mesothelial cells (PMCs) and human PMCs were used for analysis in vitro. Several molecular biological techniques were applied to uncover the potential mechanisms of ligustrazine in preventing PPA. And molecular docking and site-directed mutagenesis assay were used to predict the binding sites of ligustrazine with PPARγ. The bioinformatics analysis was further applied to identify the key pathway in the pathogenesis of PPA. Besides, PPA rodent models were prepared and developed to evaluate the novel ligustrazine nanoparticles in vivo. Ligustrazine could significantly suppress hypoxia-induced PMC functions, such as restricting the production of profibrotic cytokines, inhibiting the expression of migration and adhesion-associated molecules, repressing the expression of cytoskeleton proteins, restricting hypoxia-induced PMCs to obtain myofibroblast-like phenotypes, and reversing ECM remodeling and EMT phenotype transitions by activating PPARγ. The antagonist GW9662 of PPARγ could restore the inhibitory effects of ligustrazine on hypoxia-induced PMC functions. The inhibitor KC7F2 of HIF-1α could repress hypoxia-induced PMC functions, and ligustrazine could downregulate the expression of HIF-1α, which could be reversed by GW9662. And the expression of HIF-1α inhibited by ligustrazine was dramatically reversed after transfection with si-SMRT. The results showed that the benefit of ligustrazine on PMC functions is contributed to the activation of PPARγ on the transrepression of HIF-1α in an SMRT-dependent manner. Molecular docking and site-directed mutagenesis tests uncovered that ligustrazine bound directly to PPARγ, and Val 339/Ile 341 residue was critical for the binding of PPARγ to ligustrazine. Besides, we discovered a novel nanoparticle agent with sustained release behavior, drug delivery efficiency, and good tissue penetration in PPA rodent models. Our study unravels a novel mechanism of ligustrazine in preventing PPA. The findings indicated that ligustrazine is a potential strategy for PPA formation and ligustrazine nanoparticles are promising agents for preclinical application.

[Ultrasound-guided local injection of dexamethasone and lidocaine into subcapsule for subacute thyroiditis].

Objective:To compare the efficacy and safety of ultrasound-guided local injection of the mixture of dexamethasone（DEX） with lidocaine and oral prednisolone（PSL） in treating patients with subacute thyroiditis. Methods:Ninety-three patients with subacute thyroiditis were divided into group A（n=48） and Group B（n=45）. Group A was treated with ultrasound-guided subcapsular injection in thyroid lesion area, while group B was treated with oral medication. The pain relief time, the duration of treatment, thyroid function recovery, recurrence rate, concurrent hypothyroidism, and drug side effects were compared between the two groups. Results:After 6 months of follow-up, the pain relief time, the duration of treatment and thyroid function recovery in group A were significantly shorter than those in group B （P<0.05）, but not the recurrence rate and hypothyroidism（P>0.05）. Conclusion:Compared with oral PSL treatment, ultrasound-guided local injection of DEX and lidocaine mixture can quickly relieve pain, shorter the duration of treatment and lower adverse reactions.

Zinc- and strontium- co-incorporated nanorods on titanium surfaces with favorable material property, osteogenesis, and enhanced antibacterial activity.

Early infection and peri-implantitis after implant restoration are major reasons for dental implant failure. Implant-associated infections are majorly attributed to biofilm formation. In this study, co-incorporated zinc- (Zn-) and strontium- (Sr-) nanorod coating on sandblasted and acid-etched (SLA) titanium (SLA-Zn/Sr) was fabricated by hydrothermal synthesis. It was aimed at promoting osteogenesis while inhibiting biofilm formation. The nanorod-like particles (φ 30-50 nm) were found to be evenly formed on SLA-Zn/Sr (Zn: 1.49 ± 0.16 wt%; Sr: 21.69 ± 2.74 wt%) that was composed of well-crystallized ZnTiO3 and SrTiO3 phases. With a sufficient interface bonding strength (42.00 ± 3.00 MPa), SLA-Zn/Sr enhanced the corrosion resistance property of titanium. Besides, SLA-Zn/Sr promoted the cellular initial adhesion, proliferation and osteogenic differentiation of rBMSCs in vitro while inhibiting the adhesion of Staphylococcus aureus and Porphyromonas gingivalis . In addition, through down-regulating icaA gene expression, this novel surface reduced the secretion of polysaccharide intercellular adhesion (reduced by 87.9% compared to SLActive) to suppress the S. aureus biofilm formation. We, therefore, propose a new chemical modification on titanium for multifunctional implant material development. Due to the Zn/Sr co-doping in coating, material properties, early osteogenic effect and antibacterial ability of titanium can be simultaneously enhanced, which has the potential to be applied in dental implantation in the future.

GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus mediates nerve injury-induced neuropathic pain in rats.

The present study was aimed to investigate the role of GluN2B-BDNF pathway in the cerebrospinal fluid-contacting nucleus (CSF-CN) in neuropathic pain. Intra-lateral ventricle injection of cholera toxin subunit B conjugated with horseradish peroxidase (CBHRP) was used to label the CSF-CN. Double-labeled immunofluorescent staining and Western blot were used to observe the expression of GluN2B and BDNF in the CSF-CN. Chronic constriction injury of sciatic nerve (CCI) rat model was used to duplicate the neuropathic pain. Pain behavior was scored to determine the analgesic effects of GluN2B antagonist Ro 25-6981 and BDNF neutralizing antibody on CCI rats. GluN2B and BDNF were expressed in the CSF-CN and their expression was up-regulated in CCI rats. Intra-lateral ventricle injection of GluN2B antagonist Ro 25-6981 or BDNF neutralizing antibody notably alleviated thermal hyperalgesia and mechanical allodynia in CCI rats. Moreover, the increased expression of BDNF protein in CCI rats was reversed by intra-lateral ventricle injection of Ro 25-6981. These results suggest that GluN2B and BDNF are expressed in the CSF-CN and alteration of GluN2B-BDNF pathway in the CSF-CN is involved in the modulation of the peripheral neuropathic pain.