Jianwei Xiaoyan Granule ameliorates chronic atrophic gastritis by regulating HIF-1α-VEGF pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianwei Xiaoyan Granule (JWXYG) is the traditional Chinese medicine preparation in Jiangyin Hospital Affiliated to Nanjing University of Chinese Medicine, which has been widely used in clinical treatment of chronic atrophic gastritis (CAG). However, the material basis and potential mechanism of JWXYG in the treatment of CAG are not clear. PURPOSE: To explore the material basis and potential mechanism of JWXYG in the treatment of CAG. METHODS: In this study, the components of JWXYG were analyzed by HPLC-Q-TOF-MS/MS. Then, the CAG model in rats established by a composite modeling method and MC cell model induced by MNNG were used to explore the improvement effect of JWXYG on CAG. Finally, the potential mechanism of JWXYG in the treatment of CAG was preliminarily predicted based on network pharmacology and validated experimentally. RESULTS: Thirty-one components of JWXYG were analyzed through HPLC-Q-TOF-MS/MS, such as albiflorin, paeoniflorin, lobetyolin firstly. Research results in vivo showed that the gastric mucosa became thinner, intestinal metaplasia appeared, the number of glands was reduced, the serum levels of PG I and PG II increased and the contents of G17 and IL-6 reduced in CAG model rats. After 4 weeks of JWXYG (2.70 g/kg) administration, these conditions were significantly improved. In addition, cell viability, migration, and invasion of MNNG-induced MC cells was inhibited by JWXYG treatment (800 µg/mL). Furthermore, the results of network pharmacology indicated that HIF-1 and VEGF signaling pathways might play important roles in the therapeutic process. Then the results of western blot, immunohistochemistry and immunofluorescence confirmed that with JWXYG treatment, the increased expression of HIF-1α, VEGF and VEGFR2 in gastric issue of CAG rats were restrained. Eventually, potential components of JWXYG in the treatment of CAG were predicted through molecular docking to elucidate the material basis. CONCLUSION: JWXYG could inhibit angiogenesis by regulating HIF-1α-VEGF pathway to exert therapeutic effects on CAG. Our study explored the potential mechanisms and material basis of JWXYG in the treatment of CAG and provides experimental data for the clinical rational application of JWXYG.

Lineage-Specific Mesenchymal Stromal Cells Derived from Human iPSCs Showed Distinct Patterns in Transcriptomic Profile and Extracellular Vesicle Production.

Over the past decades, mesenchymal stromal cells (MSCs) have been extensively investigated as a potential therapeutic cell source for the treatment of various disorders. Differentiation of MSCs from human induced pluripotent stem cells (iMSCs) has provided a scalable approach for the biomanufacturing of MSCs and related biological products. Although iMSCs shared typical MSC markers and functions as primary MSCs (pMSCs), there is a lack of lineage specificity in many iMSC differentiation protocols. Here, a stepwise hiPSC-to-iMSC differentiation method is employed via intermediate cell stages of neural crest and cytotrophoblast to generate lineage-specific MSCs with varying differentiation efficiencies and gene expression. Through a comprehensive comparison between early developmental cell types (hiPSCs, neural crest, and cytotrophoblast), two lineage-specific iMSCs, and six source-specific pMSCs, are able to not only distinguish the transcriptomic differences between MSCs and early developmental cells, but also determine the transcriptomic similarities of iMSC subtypes to postnatal or perinatal pMSCs. Additionally, it is demonstrated that different iMSC subtypes and priming conditions affected EV production, exosomal protein expression, and cytokine cargo.

INDUCED PLURIPOTENT STEM CELL-DERIVED MESENCHYMAL STEM CELLS-DERIVED EXTRACELLULAR VESICLES ATTENUATE LPS-INDUCED LUNG INJURY AND ENDOTOXEMIA IN MICE.

ABSTRACT: Introduction: We hypothesized extracellular vesicles (EVs) from preconditioned human-induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) attenuate LPS-induced acute lung injury (ALI) and endotoxemia. Methods: iMSCs were incubated with cell stimulation cocktail (CSC) and EVs were isolated. iMSC-EVs were characterized by size and EV markers. Biodistribution of intratracheal (IT), intravenous, and intraperitoneal injection of iMSC-EVs in mice was examined using IVIS. Uptake of iMSC-EVs in lung tissue, alveolar macrophages, and RAW264.7 cells was also assessed. C57BL/6 mice were treated with IT/IP iMSC-EVs or vehicle ± IT/IP LPS to induce ALI/acute respiratory distress syndrome and endotoxemia. Lung tissues, plasma, and bronchoalveolar lavage fluid (BALF) were harvested at 24 h. Lung histology, BALF neutrophil/macrophage, cytokine levels, and total protein concentration were measured to assess ALI and inflammation. Survival studies were performed using IP LPS in mice for 3 days. Results: iMSC-EV route of administration resulted in differential tissue distribution. iMSC-EVs were taken up by alveolar macrophages in mouse lung and cultured RAW264.7 cells. IT LPS-treated mice demonstrated marked histologic ALI, increased BALF neutrophils/macrophages and protein, and increased BALF and plasma TNF-α/IL-6 levels. These parameters were attenuated by 2 h before or 2 h after treatment with IT iMSC-EVs in ALI mice. Interestingly, the IT LPS-induced increase in IL-10 was augmented by iMSC-EVs. Mice treated with IP LPS showed increases in TNF-α and IL-6 that were downregulated by iMSC-EVs and LPS-induced mortality was ameliorated by iMSC-EVs. Administration of IT iMSC-EVs 2 h after LPS downregulated the increase in proinflammatory cytokines (TNF-α/IL-6) by LPS and further increased IL-10 levels. Conclusions: iMSC-EVs attenuate the inflammatory effects of LPS on cytokine levels in ALI and IP LPS in mice. LPS-induced mortality was improved with administration of iMSC-EVs.

Microbial response and recovery strategy of the anammox process under ciprofloxacin stress from pure strain and consortia perspectives.

Ciprofloxacin (CIP) poses a high risk of resistance development in water environments. Therefore, comprehensive effects and recovery strategies of CIP in anaerobic ammonia oxidation (anammox) process were systematically elucidated from consortia and pure strains perspectives. The anammox consortia was not significantly affected by the stress of 10 mg L-1 CIP, while the higher concentration (20 mg L-1) of CIP caused a dramatic reduction in the nitrogen removal performance of anammox system. Simultaneously, the abundances of dominant functional bacteria and corresponding genes also significantly decreased. Such inhibition could not be mitigated by the recovery strategy of adding hydrazine and hydroxylamine. Reducing nitrogen load rate from 5.1 to 1.4 kg N m-3 d-1 promoted the restoration of three reactors. In addition, the robustness and recovery of anammox systems was evaluated using starvation and shock strategies. Simultaneously, antibiotic resistance genes and key metabolic pathways of anammox consortia were upregulated, such as carbohydrate and energy metabolisms. In addition, 11 pure stains were isolated from the anammox system and identified through phylogenetic analysis, 40 % of which showed multidrug resistance, especially Pseudomonas. These findings provide deep insights into the responding mechanism of anammox consortia to CIP stress and promote the application of anammox process for treating wastewater containing antibiotics.

Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

Femtosecond Laser Combined with Hydrothermal Method to Construct Three-Dimensional Spatially Distributed Wurtzite ZnO Micro/Nanostructures to Enhance Photocatalytic Properties.

Conventional approaches employing nanopowder particles or deposition photocatalytic nanofilm materials encounter challenges such as performance instability, susceptibility to detachment, and recycling complications in practical photocatalytic scenarios. In this study, a novel fabrication strategy is proposed that uses femtosecond laser direct writing of self-sourced metal to prepare a self-supporting microstructure substrate and combines the hydrothermal method to construct a three-dimensional spatially distributed metal oxide micro/nanostructure. The obtained wurtzite ZnO micro/nanostructure has excellent wetting properties while obtaining a larger specific surface area and can achieve effective adsorption of methyl orange molecules. Moreover, the tight integration of ZnO with the surface interface of the self-sourced metal microstructure substrate will facilitate efficient charge transfer. Simultaneously, it improves the efficiency of light utilization (absorption) and the number of active sites in the photocatalytic process, ultimately leading to excellent photodegradation stability. This result provides an innovative technology solution for achieving efficient semiconductor surface-interface photocatalytic performance and stability.

Effects of Fish Oil Supplementation on Reducing the Effects of Paternal Obesity and Preventing Fatty Liver in Offspring.

Nonalcoholic fatty liver disease (NAFLD) is a serious public health concern, which calls for appropriate diet/nutrition intervention. Fish oil (FO) has several benefits in reducing obesity, but its intergenerational role in reducing the effects of paternal obesity has not been established. Hence, we hypothesized that FO supplementation to an obese father during the pre-conceptional period could improve the metabolic health of the offspring, specifically in the liver. Three groups of male mice were fed with a low-fat (LF), high-fat (HF), or high-fat diet supplemented with FO (HF-FO) for 10 weeks and were then allowed to mate with female mice fed a chow diet. Offspring were sacrificed at 16 weeks. The liver tissue was harvested for genomic and histological analyses. The offspring of HF and HF-FO fathers were heavier compared to that of the LF mice during 9-16 weeks. The glucose tolerance of the offspring of HF-FO fathers were significantly improved as compared to the offspring of HF fathers. Paternal FO supplementation significantly lowered inflammation and fatty acid synthesis biomarkers and increased fatty acid oxidation biomarkers in the offspring liver. In summary, FO supplementation in fathers shows the potential to reduce metabolic and cardiovascular diseases through genetic means in offspring.

Morphological Awareness and DHH Students' Reading-Related Abilities: A Meta-Analysis of Correlations.

This article presents the first meta-analysis on correlations of morphological awareness (MA) with reading-related abilities in deaf and hard-of-hearing (DHH) students (k = 14, N = 556). The results showed high mean correlations of MA with all three reading-related abilities: rs = 0.610, 0.712, and 0.669 (all ps < 0.001), respectively, for word reading, vocabulary knowledge, and reading comprehension. A set of moderator analysis was conducted of language, DHH students' age/reading stage and degree of hearing loss, and task type. The correlation of MA with word reading was significantly stronger in alphabetic than in non-alphabetic languages, and for fluency than accuracy; for vocabulary knowledge, the correlation was significantly stronger for production MA tasks than for judgment tasks; for reading comprehension, derivational MA tasks showed a stronger correlation than those having a mixed focus on inflection and derivation. While no other moderator effects were significant, the correlations for subsets of effect sizes were largely high for a moderator. These findings reaffirmed the importance of morphology in DHH students' reading development. The present synthesis, while evidencing major development of research on the metalinguistic underpinnings of reading in DHH students, also showed that the literature on MA is still very limited.

The mTORC1 pathway participate in hyper-function of B cells in immune thrombocytopenia.

B cell hyper-function plays an important role in the pathogenesis of immune thrombocytopenia (ITP), but the molecular mechanisms underlying such changes remain unclear. We sought to identify regulators of B cell dysfunction in ITP patients through transcriptome sequencing and the use of inhibitors. B cells were isolated from PBMC of 25 ITP patients for B cell function test and transcriptome sequencing. For the potential regulatory factors identified by transcriptome sequencing, the corresponding protein inhibitors were used to explore the regulatory effect of the regulatory factors on B cell dysfunction in vitro. In this study, increased antibody production, enhanced terminal differentiation and highly expressed costimulatory molecules CD80 and CD86 were found in B cells of patients with ITP. In addition, RNA sequencing revealed highly activated mTOR pathway in these pathogenic B cells, indicating that the mTOR pathway may be involved in B cell hyper-function. Furthermore, mTOR inhibitors rapamycin or Torin1 effectively blocked the activation of mTORC1 in B cells, resulting in reduce antibody secretion, impaired differentiation of B cells into plasmablasts and downregulation of costimulatory molecules. Interestingly, as an unspecific inhibitor of mTORC2 besides mTORC1, Torin1 did not show a stronger capacity to modulate B cell function than rapamycin, suggesting that the regulation of B cells by Torin1 may depend on blockade of mTORC1 rather than mTORC2 pathway. These results indicated that the activation of mTORC1 pathway is involved in B cell dysfunction in patients with ITP, and inhibition of mTORC1 pathway might be a potential therapeutic approach for ITP.

Quality-Related Process Monitoring and Diagnosis of Hot-Rolled Strip Based on Weighted Statistical Feature KPLS.

Rolling is the main process in steel production. There are some problems in the rolling process, such as insufficient ability of abnormal detection and evaluation, low accuracy of process monitoring, and fault diagnosis. To improve the accuracy of quality-related fault diagnosis, this paper proposes a quality-related process monitoring and diagnosis method for hot-rolled strip based on weighted statistical feature KPLS. Firstly, the process-monitoring and diagnosis model of strip thickness and quality based on the KPLS method is introduced. Then, considering that the KPLS diagnosis method ignores the contribution of process variables to quality, it is easy to misjudge the root cause of quality in the diagnosis process. Based on the rolling mechanism model, the influence weight of strip thickness is constructed. By weighing the statistical data features, a quality diagnosis framework of series structure data fusion is constructed. Finally, the method is applied to the 1580 mm hot-rolling process for industrial verification. The verification results show that the proposed method has higher diagnostic accuracy than PLS, KPLS, and other methods. The results show that the diagnostic model based on weighted statistical feature KPLS has a diagnostic accuracy of more than 96% for strip thickness and quality-related faults.

A novel prognostic signature based on immunogenic cell death score predicts outcomes and response to transcatheter arterial chemoembolization and immunotherapy in hepatocellular carcinoma.

PURPOSE: The phenomenon of immunogenic cell death (ICD) is intricately linked to numerous antitumor treatments and exerts a profound regulatory function in the tumor immune microenvironment (TIME). We aimed to establish a prognostic signature from the ICD-related biomarkers to differentiate the TIME in hepatocellular carcinoma and predict diverse outcomes for patients with liver cancer. METHODS: ICD score-related genes (ICDSGs) were identified using the weighted gene co-expression network analysis (WGCNA). The ICD score-related signature (ICDSsig) was established by applying LASSO and Cox regression. Model precision was verified using the external datasets. We used independent prognostic variables in clinicopathologic factors to develop a nomogram. Further, clinical characteristics, immune and molecular landscapes, the responses of transcatheter arterial chemoembolization (TACE) and immunotherapy, and chemotherapy sensitivity were analyzed for high- and low-risk patients. RESULTS: ICD score-calculated using the single-sample gene set enrichment analysis (ssGSEA)-displayed strong associations with the TIME in HCC. We identified 34 ICDSGs after integrating the TCGA and GSE104580 datasets. Then, three novel ICDSGs (DNASE1L3, KLRB1, and LILRB1) were screened out to construct the ICDSsig; the prognostic signature performed well in the external databases. The high-risk patients had worse outcomes owing to their advanced pathological state, non-response of TACE, and immune-cold phenotype in the immune landscapes. The immune checkpoint genes, N6-methyladenosine-relevant genes, and microsatellite instability score were increased in the high-risk subgroup, thereby indicating a favorable sensitivity to immunotherapy. Common chemotherapy drugs were more effective in high-risk patients due to low half-maximal inhibitory concentration values. CONCLUSION: The ICDSsig can potentially predict outcomes and therapeutic responses for patients with liver cancer and may assist clinicians in designing individualized treatment strategies.

Selective transformation and removal of As(III) by constructed Fe-N bonds: The generation of singlet oxygen from the photoexcitation of MnPc leads to abundant ZnFe-LDH interface OH radical.

In this study, MnPc intercalated Zn/Fe layered double hydroxides (MnPc/ZF-LDH) were synthesized by pillared intercalation modification with different MnPc intercalation amounts and used for the selective transformation and removal of As(III) from the arsenate-phosphate mixed solution. Fe-N bonds were constructed by the complexation of MnPc and iron ions on the Zn/Fe layered double hydroxides (ZF-LDH) interface. The DFT calculation results show that the binding energy of Fe-N bonded to arsenite (-3.75 eV) was higher than that of phosphate (-3.16 eV), resulting in MnPc/ZnFe-LDH exhibiting high As(III) selective adsorption performance and anchoring it rapidly in the arsenite -phosphate mixed solution. The maximum adsorption capacity of 1MnPc/ZF-LDH for As(III) could reach 180.7 mg·g-1 under dark conditions. MnPc also acts as a photosensitizer to provide more active species for the photocatalytic reaction. A series of experiments demonstrated that MnPc/ZF-LDH exhibits high As(III) selective photocatalytic performance. A total of 10 mg·L-1 of As(III) was completely removed in the reaction system within 50 min in a single As(III) environment. In an environment with As(III) and PO43-, it achieved 80.0 % removal efficiency of As(III) and showed a good reuse effect. The introduction of MnPc could improve the utilization of visible light by the MnPc/ZnFe-LDH. The singlet oxygen generated from photoexciting MnPc leads to abundant ZnFe-LDH interface OH. In addition, MnPc/ZnFe-LDH shows good recyclability, making it a promising multifunctional material for the purification of arsenic-polluted sewage.

Differing postural control patterns in individuals with bilateral and unilateral hearing loss.

OBJECTIVES: Hearing loss (HL) is associated with imbalance and increased fall risk. The mechanism underlying this relationship and differences across types of hearing loss remains unclear. Head mounted displays (HMD) can shed light on postural control mechanisms via an analysis of head sway. PURPOSE: The purpose of this study was to evaluate head sway in response to sensory perturbations in individuals with bilateral (BHL) or unilateral hearing loss (UHL) and compare them to controls. MATERIALS AND METHODS: We recruited 36 controls, 23 individuals with UHL and 14 with BHL. An HMD (HTC Vive) measured head sway while participants stood on the floor, hips-width apart. Stimuli included two levels of visuals and sound. Root Mean Square Velocity (RMSV) and Power Spectral Density (PSD) were used to quantify head sway. RESULTS: Adjusting for age, individuals with BHL had significantly higher anterior-posterior and medio-lateral RMSV than controls and individuals with UHL. Individuals with UHL demonstrated significantly lower response to visual perturbations in RMSV AP and in all 3 frequency segments of PSD compared to controls. Individuals with UHL showed significantly lower movements at high frequencies compared to controls. Sounds or severity of HL did not impact head sway. CONCLUSIONS: Individuals with BHL demonstrated increased sway with visual perturbations and should be clinically assessed for balance performance and fall risk. Individuals with UHL exhibited reduced responses to visual stimuli compared with controls, which may reflect conscious movement processing. Additional studies are needed to further understand the mechanistic relationship between hearing loss and imbalance.

A novel nomogram to predict survival of patients with hepatocellular carcinoma after transarterial chemoembolization: a tool for retreatment decision making.

Background: There is still no standardized policy regarding how to identify patients who are not benefiting from transarterial chemoembolization (TACE). We aimed to establish and validate a nomogram model to predict the survival rate of hepatocellular carcinoma (HCC) patients after TACE. Methods: A total of 578 HCC patients undergoing initial TACE at the First Affiliated Hospital of Wenzhou Medical University were retrospectively recruited to the study. The patients were randomly divided into 2 cohorts: a training cohort (n=405) and a validation cohort (n=173). To develop the nomogram, Cox regression analyses were used to identify independent risk factors. The performances of the nomogram were assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA), and were compared to 4 developed prognostic models. Results: We used 5 independent risk factors including postoperative albumin-bilirubin (ALBI) grade, tumor diameter, number of tumors, portal vein invasion, and tumor response to develop the nomogram. Calibration curves showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.753 [95% confidence interval (CI): 0.722, 0.784], which was higher than the other prognostic models (P<0.001). The DCA showed that the nomogram had the highest net benefit among the models. According to predicted survival risk, the nomogram could divide patients into 3 groups (P<0.001). All the results were verified in the validation cohort. Conclusions: This study developed and validated a nomogram model for HCC patients undergoing TACE, which could predict the survival rate and provide support for further treatment strategies.

Highly sensitive detection of low-concentration sodium chloride solutions based on polymeric nanofilms coated long period fiber grating.

Long period fiber gratings (LPFGs) have special advantages in the detection of salt concentrations due to small volume, corrosion resistance and immunity to electromagnetic interference. However, it is very difficult to distinguish low-concentration salt solutions with usual LPFGs owing to the poor sensitivity. In this paper, the detection capability of the LPFG to low-concentration salt solutions was significantly improved by assembling salt-containing poly (diallyldimethylammonium chloride) (PDDA) and salt-containing poly (sodium-p-styrenesulfonate) (PSS). Experimental results showed that, the responsive wavelength range of the LPFG was remarkably broadened in low-concentration salt solutions after assembling nanofilms. The suitable detection range of the PDDA/PSS films coated LPFG for salt concentrations was 0-3%. In such a range, the average refractive index sensitivity and the average salinity sensitivity of the LPFG was as high as 29545.9 nm/RIU and 52.2 nm/% respectively. Compared with the LPFG without nanofilms, the discrimination ability of the PDDA/PSS films coated LPFG to 0-3% salt solutions increased by 568 times. The analysis demonstrated that PDDA and salt in the assembly solutions played a pivotal role in the above effects. The proposed sensor has extensive application prospects in the monitoring of salt concentration in many fields such as seawater, food processing, fermentation process, etc.

Deciphering the chemical composition of Ganoderma lucidum from different geographical origins by mass spectrometry molecular networking coupled with multivariate analysis.

Ganoderma lucidum is a medicinal fungus that has been widely used in China and many Asian countries for thousands of years. This once rare macrofungus has now been artificially cultivated in a number of regions in China. However, detailed knowledge of its composition across different geographical origins is still lacking, as are analytical methods for comprehensive profiling of the diverse phytochemicals contained in G. lucidum. In this work, an on-demand strategy based on high-resolution MS and molecular networking is applied for natural product characterization, which led to the identification of 84 constituents in G. lucidum. Moreover, multivariate analysis, including hierarchical cluster analysis and orthogonal partial least squares-discriminant analysis, was used to analyze the (dis)similarity of the G. lucidum samples collected from the three main production areas (i.e., Jilin, Henan and Shandong Province). The results revealed a significant variation in the chemical composition of samples from different provinces. Marker constituents corresponding to the differentiation were then screened in terms of the variable importance in projection value, P-value and fold change. A total of 24 constituents were identified as geoherbalism markers, such as ganoderenic acid A for Henan, ganolucidic acid B for Jilin and ganodernoid D for Shandong. This proof-of-concept application demonstrates that combining MS molecular networking with meticulous multivariate analysis can provide a sensitive and comprehensive analytical approach for the quality assessment of traditional Chinese medicine ingredients. This study also suggests that the bioactivity and efficacy from different origins should be further evaluated considering the large difference in chemical compositions.

Investigation of macrophage polarization in herniated nucleus pulposus of patients with lumbar intervertebral disc herniation.

Macrophage infiltration and polarization during lumbar intervertebral disc herniation (LDH) have attracted increased attention but their role remains unclear. To explore macrophage polarization in herniated nucleus pulposus (NP) tissue of patients with LDH and investigate the association between cell frequency and different clinical characteristics or symptoms, we conducted a retrospective study by analyzing NP tissue samples from 79 patients. Clinical features and symptoms, using the visual analog scale (VAS) and Oswestry disability index (ODI), were collected. The macrophage markers CD68, CCR7, CD163, and CD206; pro-inflammatory cytokine TNF-α; and anti-inflammatory factor IL-4 were analyzed by immunohistochemistry. The frequency of polarized macrophages and positivity rate of pro- and anti-inflammatory cytokines showed significant differences in some of clinical characteristics. Specifically, higher CCR7+ and TNF-α + proportions were identified in the high-intensity zone (HIZ) and the type of extrusion and sequestration NP tissue than in non-HIZ and protrude NP tissue. Higher CD206+ and IL-4+ proportion were detected in Modic changes. However, no differences in gender, age, smoking status, Pfirrmann grade, analgesic use, leg pain duration, and segments were found between groups. CD68+ , CCR7+ , and CD206+ cell proportions, and TNF-α and IL-4 showed positive associations with VAS scores preoperation. Associations between ODI and the macrophages markers were weak/insignificant. Our results indicated that macrophage polarization or macrophage-like cells contribute to LDH pathological features. Macrophage populations displaying significant associations with VAS score reflected continuous M1/M2 transition contributing to pain during LDH. These findings may contribute to enhanced/personalized pharmacological interventions for patients with LDH considering pain heterogeneity.

Role of quorum sensing-based regulation in development of anaerobic ammonium oxidation process.

Shortage of anaerobic ammonium oxidation (anammox) sludge greatly limits the extensive full-scale application of anammox-based processes. Although numerous start-up strategies have been proposed, the interaction among microbial consortia and corresponding mechanism during the process development remain unknown. In this study, three reactors were established based on different seed sludges. After 27 days, the anammox process inoculated with anammox granules and activated sludge (1:5) was firstly achieved, and the highest nitrogen removal rate was 1.17 kg N m-3 d-1. Correspondingly, the anammox activity and abundances of related functional genes increased. Notably, the dominant anammox bacteria shifted from Candidatus Kuenenia to Candidatus Brocadia. Metagenomic analysis indicated that quorum sensing-based regulation mainly contributed to the proliferation and accumulation of anammox bacteria. This work provides an insight into the quorum sensing (QS)-regulated microbial interactions in the anammox and activated sludge consortia during the process development.

Smart Lattice Structures with Self-Sensing Functionalities via Hybrid Additive Manufacturing Technology.

Lattice structures are a group of cellular materials composed of regular repeating unit cells. Due to their extraordinary mechanical properties, such as specific mechanical strength, ultra-low density, negative Poisson's ratio, etc., lattice structures have been widely applied in the fields of aviation and aerospace, medical devices, architecture, and automobiles. Hybrid additive manufacturing (HAM), an integrated manufacturing technology of 3D printing processes and other complementary processes, is becoming a competent candidate for conveniently delivering lattice structures with multifunctionalities, not just mechanical aspects. This work proposes a HAM technology that combines vat photopolymerization (VPP) and electroless plating process to fabricate smart metal-coated lattice structures. VPP 3D printing process is applied to create a highly precise polymer lattice structure, and thereafter electroless plating is conducted to deposit a thin layer of metal, which could be used as a resistive sensor for monitoring the mechanical loading on the structure. Ni-P layer and copper layer were successfully obtained with the resistivity of 8.2×10-7Ω⋅m and 2.0 ×10-8 Ω⋅m, respectively. Smart lattice structures with force-loading self-sensing functionality are fabricated to prove the feasibility of this HAM technology for fabricating multifunctional polymer-metal lattice composites.

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer.

Liver cancer is an extraordinarily heterogeneous malignant disease. The tumor microenvironment (TME) and tumor-associated macrophages (TAMs) are the major drivers of liver cancer initiation and progression. It is critical to have a better understanding of the complicated interactions between liver cancer and the immune system for the development of cancer immunotherapy. Based on the gene expression profiles of tumor immune infiltration cells (TIICs), upregulated genes in TAMs and downregulated genes in other types of immune cells were identified as macrophage-specific genes (MSG). In this study, we combined MSG, immune subtypes, and clinical information on liver cancer to develop a tumor immune infiltration macrophage signature (TIMSig). A four-gene signature (S100A9, SLC22A15, TRIM54, and PPARGC1A) was identified as the TAM-related prognostic genes for liver cancer, independent of multiple clinicopathological parameters. Survival analyses showed that patients with low TIMSig had a superior survival rate than those with high TIMSig. Additionally, clinical immunotherapy response and TIMSig was observed as highly relevant. In addition, TIMSig could predict the response to chemotherapy. Collectively, the TIMSig could be a potential tool for risk-stratification, clinical decision making, treatment planning, and oncology immunotherapeutic drug development.