Effects of dietary ginger (Zingiber officinale) polysaccharide on the growth, antioxidant, immunity response, intestinal microbiota, and disease resistance to Aeromonas hydrophila in crucian carp (Carassius auratus).

Ginger polysaccharides (GP) promote growth and development in fish. However, the effects of GP on crucian carp remain unclear. The present study investigated the effects of GP on the growth performance, immunity, intestinal microbiota, and disease resistance in crucian carp. Four treatment groups were established with different concentrations of GP (0.1 %, 0.2 %, 0.4 %, and 0.8 %). GP was not added as the control group, and the feeding period lasted for 56 d, followed by a 96-h anti-infection treatment using Aeromonas hydrophila. The results showed that dietary GP significantly improved growth performance, especially in the 0.4 % GP group. Furthermore, GP administration notably increased serum lysozyme (LMZ) activity, digestive enzyme performance, and antioxidant capacity of crucian carp. Moreover, dietary inclusion of GP up-regulated the expression of tumour necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFN-γ), and nuclear factor kappa-B (NF-κB) genes while down-regulating IL-10 and transforming growth factor-ß (TGF-ß) gene expressions, thus promoting liver health in crucian carp. Additionally, incorporating GP into the diet regulated both the diversity and composition of the intestinal microbiota in crucian carp, explicitly enhancing the relative abundance of beneficial bacteria, such as Fusobacteriota and Firmicutes. Therefore, GP reduces the mortality of crucian carp infected with A. hydrophila. In conclusion, this study provides novel insights into the application of dietary GP in cultured fish and evaluates the value of traditional Chinese medicinal polysaccharides against pathogenic bacteria.

Dietary intake, antioxidants, minerals and vitamins in relation to childhood asthma: a Mendelian randomization study.

Background: Currently, there is limited and inconsistent evidence regarding the risk association between daily dietary intake, antioxidants, minerals, and vitamins with Childhood Asthma (CA). Therefore, this study employs Mendelian Randomization (MR) methodology to systematically investigate the causal relationships between daily dietary intake, serum antioxidants, serum minerals, and the circulating levels of serum vitamins with CA. Methods: This study selected factors related to daily dietary intake, including carbohydrates, proteins, fats, and sugars, as well as serum antioxidant levels (lycopene, uric acid, and ß-carotene), minerals (calcium, copper, selenium, zinc, iron, phosphorus, and magnesium), and vitamins (vitamin A, vitamin B6, folate, vitamin B12, vitamin C, vitamin D, and vitamin E), using them as Instrumental Variables (IVs). Genetic data related to CA were obtained from the FinnGen and GWAS Catalog databases, with the primary analytical methods being Inverse Variance Weighting (IVW) and sensitivity analysis. Results: Following MR analysis, it is observed that sugar intake (OR: 0.71, 95% CI: 0.55-0.91, P: 0.01) is inversely correlated with the risk of CA, while the intake of serum circulating magnesium levels (OR: 1.63, 95% CI: 1.06-2.53, P: 0.03), fats (OR: 1.44, 95% CI: 1.06-1.95, P: 0.02), and serum vitamin D levels (OR: 1.14, 95% CI: 1.04-1.25, P: 0.02) are positively associated with an increased risk of CA. Conclusion: This study identified a causal relationship between the daily dietary intake of sugars and fats, as well as the magnesium and vitamin D levels in serum, and the occurrence of CA. However, further in-depth research is warranted to elucidate the specific mechanisms underlying these associations.

Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.

Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.

Natural History and Outcomes of Individuals With Functional Bowel Disorder: A 9-year Population-Based Longitudinal Study.

INTRODUCTION: Long-term studies characterizing the natural history of functional bowel disorder (FBD) from community-based settings and exploring association with psychological factors are sparse. We aimed to evaluate the evolution of symptoms, health outcomes, and association of FBD with psychological disorders in Chinese population. METHODS: Individuals identified from random sampling of residents of Hangzhou, China, participated in a baseline survey in January 2010. Follow-up phone survey was conducted in December 2018. FBD was diagnosed based on Rome III criteria. RESULTS: Among 452 individuals (mean age 44.6 ± 15.3 years, 174 [38%] male) who completed the study, the prevalence of FBD was 36.3% (95% confidence interval [CI] 32.6-40.0%) at enrollment and 36.1% (95% CI 32.3-39.8%) at follow-up survey ( P = 0.94). However, 214 individuals (47%) had interval change in diagnosis. Although no difference in incidence of organic disease or death was observed, a higher proportion of patients with FBD (16/164, 9.8% vs 9/288, 3.1%; P = 0.003) compared with those without FBD received non-cancer-related abdominal and/or pelvic surgery during follow-up. FBD was associated with anxiety and/or depression at initial (adjusted odds ratio [AOR] = 1.7, 95% CI 1.7-2.7, P = 0.02) and follow-up (AOR = 8.0, 95% CI 3.2-20.0, P < 0.001) surveys. Diagnosis of FBD at baseline was associated with new-onset anxiety and/or depression at follow-up (AOR = 3.2, 95% CI 1.2-8.3, P = 0.01). DISCUSSION: Although the prevalence of FBD remained stable, transformation of symptoms was common over time. Patients with FBD may have increased risk of receiving non-cancer-related abdominal and/or pelvic surgery. FBD symptoms at baseline increased the risk of new-onset anxiety and/or depression by 3.2-fold over the next 9 years.

Untargeted LC-MS metabolomics reveals the metabolic responses in the Eriocheir sinensis gills exposed to salinity and alkalinity stress.

In recent years, saline-alkaline aquaculture development has become an important measure for China to expand its fishery development space to ensure food safety. Previous studies have verified that salinity and alkalinity positively influence the quality of Chinese mitten crabs (Eriocheir sinensis). However, the regulatory mechanism of E. sinensis endures saline-alkaline stress which remains obscure. This study investigated the metabolic changes in puberty-molting E. sinensis gills exposed to freshwater (FW), sodium chloride salinity of 5 ppt (SW), and carbonate alkalinity 10.00 mmol/L (AW) for 50 days using untargeted liquid chromatography-mass spectrometry metabolomics (LC-MS). A total of 5802 (positive-ion mode) and 6520 (negative-ion mode) peaks were extracted by LC-MS, respectively. A total of 188 (50 upregulated and 138 downregulated), 141 (94 upregulated and 47 downregulated), and 130 (87 upregulated and 43 downregulated) significantly regulated metabolites (SRMs) were observed in the FW-SW, FW-AW, and SW-AW treatments, respectively, wherein 42 generic SRMs were also found by Venn diagram analysis. Seven of the top 10 SRMs with the highest (variable importance in projection) VIP values were similarly identified in FW-SW and SW-AW. Integrated analysis of key metabolic pathways revealed glycerophospholipid, choline in cancer, phenylalanine, and butanoate metabolism. Overall, significant differences were observed in the metabolites and key metabolic pathways of E. sinensis gill exposed to salinity and alkalinity stress. These results will be helpful in understanding the environmental adaptability of aquatic crustaceans to saline-alkaline water.

Carbon-Iodine Polydiacetylene Nanofibers for Image-Guided Radiotherapy and Tumor-Microenvironment-Enhanced Radiosensitization.

Radiotherapy is a mainstay treatment used in clinics for locoregional therapy, although it still represents a great challenge to improve the sensitivity and accuracy of radiotherapy for tumors. Here, we report the conjugated polymer, polydiiododiacetylene (PIDA), with an iodine content of 84 wt %, as a highly effective computed tomography (CT) contrast agent and tumor microenvironment-responsive radiosensitizer. PIDA exhibited several key properties that contribute to the improvement of precision radiotherapy. The integrated PIDA nanofibers confined within the tumor envelope demonstrated amplified CT intensity and prolonged retention, providing an accurate calculation of dose distribution and precise radiation delivery for CT image-guided radiotherapy. Therefore, our strategy pioneers PIDA nanofibers as a bridge to cleverly connect a fiducial marker to guide accurate radiotherapy and a radiosensitizer to improve tumor sensitivity, thereby minimizing potential damage to surrounding tissues and facilitating on-demand therapeutic intervention in tumors.

Ginger polysaccharide alleviates the effects of acute exposure to carbonate in crucian carp (Carassius auratus) by regulating immunity, intestinal microbiota, and intestinal metabolism.

Alkaline stress poses a significant challenge to the healthy growth of fish. Ginger polysaccharide (GP) is one of the main active substances in ginger and has pharmacological effects, such as anti-oxidation and immune regulation. However, the physiological regulatory mechanism of GP addition to diet on alkalinity stress in crucian carp remains unclear. This study aimed to investigate the potential protective effects of dietary GP on antioxidant capacity, gene expression levels, intestinal microbiome, and metabolomics of crucian carp exposed to carbonate (NaHCO3). The CK group (no GP supplementation) and COG group (NaHCO3 stress and no GP supplementation) were set up. The GPCS group (NaHCO3 stress and 0.4% GP supplementation) was stressed for seven days. Based on these data, GP significantly increased the activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), acid phosphatase (ACP), and alkaline phosphatase (AKP) in carp under alkalinity stress (p < 0.05) and decreased the activity of malon dialdehyde (MDA) (p < 0.05). GP restored the activity of GSH-PX, ACP, and AKP to CK levels. The expression levels of tumor necrosis factor ß (TGF-ß), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin 8 (IL-8) genes were decreased, and the expression levels of determination factor kappa-B (NF-κB) and interleukin 10 (IL-10) genes were increased (p < 0.05). Based on 16 S rRNA high-throughput sequencing, GP improved the changes in the intestinal microbial diversity and structural composition of crucian carp caused by NaHCO3 exposure. In particular, GP increased the relative abundance of Proteobacteria and Bacteroidetes and decreased the relative abundance of Actinobacteria. The metabolic response of GP to NaHCO3 exposed crucian carp guts was studied using LC/MS. Compared to the COG group, the GPCS group had 64 different metabolites and enriched 10 metabolic pathways, including lipid metabolism, nucleotide metabolism, and carbohydrate metabolism. The addition of GP to feed can promote galactose metabolism and provide an energy supply to crucian carp, thus alleviating the damage induced by alkalinity stress. In conclusion, GP can mitigate the effects of NaHCO3 alkalinity stress by regulating immune function, intestinal flora, and intestinal metabolism in crucian carp. These findings provide a novel idea for studying the mechanism of salt-alkali tolerance in crucian carp by adding GP to feed.

Erratum: [Corrigendum] PF­2341066 combined with celecoxib promotes apoptosis and inhibits proliferation in human cholangiocarcinoma QBC939 cells.

[This corrects the article DOI: 10.3892/etm.2018.5967.].

Voting based double-weighted deterministic extreme learning machine model and its application.

This study introduces an intelligent learning model for classification tasks, termed the voting-based Double Pseudo-inverse Extreme Learning Machine (V-DPELM) model. Because the traditional method is affected by the weight of input layer and the bias of hidden layer, the number of hidden layer neurons is too large and the model performance is unstable. The V-DPELM model proposed in this paper can greatly alleviate the limitations of traditional models because of its direct determination of weight structure and voting mechanism strategy. Through extensive simulations on various real-world classification datasets, we observe a marked improvement in classification accuracy when comparing the V-DPELM algorithm to traditional V-ELM methods. Notably, when used for machine recognition classification of breast tumors, the V-DPELM method demonstrates superior classification accuracy, positioning it as a valuable tool in machine-assisted breast tumor diagnosis models.

Exosomal miR-182 derived from bone marrow mesenchymal stem cells drives carfilzomib resistance of multiple myeloma cells by targeting SOX6.

BACKGROUND: Multiple myeloma (MM) is a common hematological malignancy. Drug resistance remains to be a major clinical challenge in MM therapy. In this study, we aim to investigate the functional roles of bone marrow mesenchymal stem cells (BMSC)-derived exosomal miR-182 on the carfilzomib resistance of MM and its underlying mechanism. METHODS: qRT-PCR and Western blot methods were utilized to confirm the gene or protein expressions. CCK-8 and transwell assays were performed to measure the capabilities of proliferation, migration, and invasion. The molecular interactions were validated through ChIP and Dual luciferase assay. RESULTS: Our findings indicated that miR-182 expression was upregulated in serum, BMSCs and BMSC-derived exosomes from MM patients. Hypoxia-inducible factor-1α (HIF-1α), a key transcriptional factor in tumor microenvironment, could boost miR-182 expression by directly binding to its promoter, thus favoring exosomal secretion. Moreover, exosomal miR-182 from BMSCs could be transferred to MM cells and was able to promote malignant proliferation, metastasis, and invasion, as well as decrease the sensitivity of MM cells against carfilzomib. Additionally, SOX6 was identified as a downstream target of miR-182 in MM cells, and its expression was negatively regulated by miR-182. Rescue experiments proved that loss of SOX6 in MM cells dramatically reversed the promoting roles of BMSC-secreted exosomal miR-182 on proliferation, metastasis, and carfilzomib resistance in MM cells. CONCLUSION: Collectively, our findings indicated that exosomal miR-182 derived from BMSCs contributed to the metastasis and carfilzomib resistance of MM cells by targeting SOX6. This study sheds light on the pathogenesis of the BMSC-derived exosome containing miR-182 in the malignant behaviors of MM cells and carfzomib resistance.

Evaluating the value of 18F-PSMA-1007 PET/CT in the detection and identification of prostate cancer using histopathology as the standard.

BACKGROUND: Prostate-specific membrane antigen (PSMA) PET/CT is a highly regarded radionuclide imaging modality for prostate cancer (PCa). This study aimed to evaluate the diagnostic performance of 18F-PSMA-1007 PET/CT in detecting intraprostatic lesions of PCa using radical prostatectomy (RP) specimens as a reference standard and to establish an optimal maximum standardized uptake value (SUVmax) cutoff for distinguishing between PCa and non-PCa lesions. METHODS: We retrospectively collected 117 patients who underwent 18F-PSMA-1007 PET/CT before RP. The uptake of the index tumor and contralateral non-PCa lesion was assessed. Histopathology of RP specimens was used as the gold standard. Kappa test was used to evaluate the consistency of preoperative PSMA PET/CT staging and postoperative pathological staging. Finally, an SUVmax cutoff value was identified by receiver operating characteristic (ROC) curve analysis to distinguish PCa lesions from non-PCa lesions. A prospective cohort including 76 patients was used to validate the results. RESULTS: The detection rate of 18F-PSMA-1007 PET/CT for prostate cancer was 96.6% (113/117). 18F-PSMA-1007 had a sensitivity of 91.2% and a positive predictive value (PPV) of 89.8% for the identification of intraprostatic lesions. The consistency test (Kappa = 0.305) indicated poor agreement between the pathologic T-stage and PSMA PET/CT T-stage. Based on ROC curve analysis, the appropriate SUVmax to diagnose PCa lesions was 8.3 (sensitivity of 71.3% and specificity 96.8%) with an area under the curve (AUC) of 0.93 (P < 0.001). This SUVmax cutoff discriminated PCa lesions from non-PCa lesions with a sensitivity of 74.4%, a specificity of 95.8% in the prospective validation group. CONCLUSIONS: 18F-PSMA-1007 PET/CT demonstrated excellent performance in detecting PCa. An optimal SUVmax threshold (8.3) could be utilized to identify lesions of PCa by 18F-PSMA-1007 PET/CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04521894, Registered: August 17, 2020.

Lower serum Klotho level and higher systemic immune-inflammation index: an inverse correlation.

OBJECTIVES: Klotho, an anti-aging protein, has been identified to control tissue inflammatory responses. The objective of this research is to determine the linkage between soluble Klotho (S-Klotho) level and systemic immune-inflammation index (SII). METHODS: Eligible participants with complete information of S-Klotho level and SII were selected from the National Health and Nutrition Examination Surveys (NHANES). Subsequently, weighted multivariate linear regression and subgroup analysis were carried out to evaluate the association. RESULTS: Totally, 11,108 adults with complete data on S-Klotho level, SII and other important covariates were included in final analysis. Multivariate liner regression revealed that high level of S-Klotho was associated with low level of SII after multivariate adjustments (ß=-0.08, 95%CI:-0.10- -0.05, P < 0.01). When classifying S-Klotho into tertiles, participants in S-Klotho tertile 3 (Q3) showed a decrease in SII level compared with those in the lowest tertile (Q1) (ß=-45.44, 95%CI:-64.41- -26.47, P < 0.01 ). The negative associations remained significant regardless of age and gender, and varied depending on smoking status and BMI subgroups. CONCLUSION: S-Klotho level was negatively related to SII after controlling for covariates. Further studies need to validate current findings and explore the fundamental mechanisms.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

R-Loops in Genome Instability and Cancer.

R-loops are unique, three-stranded nucleic acid structures that primarily form when an RNA molecule displaces one DNA strand and anneals to the complementary DNA strand in a double-stranded DNA molecule. R-loop formation can occur during natural processes, such as transcription, in which the nascent RNA molecule remains hybridized with the template DNA strand, while the non-template DNA strand is displaced. However, R-loops can also arise due to many non-natural processes, including DNA damage, dysregulation of RNA degradation pathways, and defects in RNA processing. Despite their prevalence throughout the whole genome, R-loops are predominantly found in actively transcribed gene regions, enabling R-loops to serve seemingly controversial roles. On one hand, the pathological accumulation of R-loops contributes to genome instability, a hallmark of cancer development that plays a role in tumorigenesis, cancer progression, and therapeutic resistance. On the other hand, R-loops play critical roles in regulating essential processes, such as gene expression, chromatin organization, class-switch recombination, mitochondrial DNA replication, and DNA repair. In this review, we summarize discoveries related to the formation, suppression, and removal of R-loops and their influence on genome instability, DNA repair, and oncogenic events. We have also discussed therapeutical opportunities by targeting pathological R-loops.

Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks.

FAAP20 is a Fanconi anemia (FA) protein that associates with the FA core complex to promote FANCD2/FANCI monoubiquitination and activate the damage response to interstrand crosslink damage. Here, we report that FAAP20 has a marked role in homologous recombination at a DNA double-strand break not associated with an ICL and separable from its binding partner FANCA. While FAAP20's role in homologous recombination is not dependent on FANCA, we found that FAAP20 stimulates FANCA's biochemical activity in vitro and participates in the single-strand annealing pathway of double-strand break repair in a FANCA-dependent manner. This indicates that FAAP20 has roles in several homology-directed repair pathways. Like other homology-directed repair factors, FAAP20 loss causes a reduction in nuclear RAD51 Irradiation-induced foci; and sensitizes cancer cells to ionizing radiation and PARP inhibition. In summary, FAAP20 participates in DNA double strand break repair by supporting homologous recombination in a non-redundant manner to FANCA, and single-strand annealing repair via FANCA-mediated strand annealing activity.

Machine-learning algorithm-based prediction of a diagnostic model based on oxidative stress-related genes involved in immune infiltration in diabetic nephropathy patients.

Diabetic nephropathy (DN) is the most prevalent microvascular consequence of diabetes and has recently risen to the position of the world's second biggest cause of end-stage renal diseases. Growing studies suggest that oxidative stress (OS) responses are connected to the advancement of DN. This study aimed to developed a novel diagnostic model based on OS-related genes. The differentially expressed oxidative stress-related genes (DE-OSRGs) experiments required two human gene expression datasets, which were given by the GEO database (GSE30528 and GSE96804, respectively). The potential diagnostic genes were identified using the SVM-RFE assays and the LASSO regression model. CIBERSORT was used to determine the compositional patterns of the 22 different kinds of immune cell fraction seen in DN. These estimates were based on the combined cohorts. DN serum samples and normal samples were both subjected to RT-PCR in order to investigate the degree to which certain genes were expressed. In this study, we were able to locate 774 DE-OSRGs in DN. The three marker genes (DUSP1, PRDX6 and S100A8) were discovered via machine learning on two different machines. The high diagnostic value was validated by ROC tests, which focused on distinguishing DN samples from normal samples. The results of the CIBERSORT study suggested that DUSP1, PRDX6, and S100A8 may be associated to the alterations that occur in the immunological microenvironment of DN patients. Besides, the results of RT-PCR indicated that the expression of DUSP1, PRDX6, and S100A8 was much lower in DN serum samples compared normal serum samples. The diagnostic value of the proposed model was likewise verified in our cohort, with an area under the curve of 9.946. Overall, DUSP1, PRDX6, and S100A8 were identified to be the three diagnostic characteristic genes of DN. It's possible that combining these genes will be effective in diagnosing DN and determining the extent of immune cell infiltration.

Photobiomodulation reduces neuropathic pain after spinal cord injury by downregulating CXCL10 expression.

BACKGROUND: Many studies have recently highlighted the role of photobiomodulation (PBM) in neuropathic pain (NP) relief after spinal cord injury (SCI), suggesting that it may be an effective way to relieve NP after SCI. However, the underlying mechanisms remain unclear. This study aimed to determine the potential mechanisms of PBM in NP relief after SCI. METHODS: We performed systematic observations and investigated the mechanism of PBM intervention in NP in rats after SCI. Using transcriptome sequencing, we screened CXCL10 as a possible target molecule for PBM intervention and validated the results in rat tissues using reverse transcription-polymerase chain reaction and western blotting. Using immunofluorescence co-labeling, astrocytes and microglia were identified as the cells responsible for CXCL10 expression. The involvement of the NF-κB pathway in CXCL10 expression was verified using inhibitor pyrrolidine dithiocarbamate (PDTC) and agonist phorbol-12-myristate-13-acetate (PMA), which were further validated by an in vivo injection experiment. RESULTS: Here, we demonstrated that PBM therapy led to an improvement in NP relative behaviors post-SCI, inhibited the activation of microglia and astrocytes, and decreased the expression level of CXCL10 in glial cells, which was accompanied by mediation of the NF-κB signaling pathway. Photobiomodulation inhibit the activation of the NF-κB pathway and reduce downstream CXCL10 expression. The NF-κB pathway inhibitor PDTC had the same effect as PBM on improving pain in animals with SCI, and the NF-κB pathway promoter PMA could reverse the beneficial effect of PBM. CONCLUSIONS: Our results provide new insights into the mechanisms by which PBM alleviates NP after SCI. We demonstrated that PBM significantly inhibited the activation of microglia and astrocytes and decreased the expression level of CXCL10. These effects appear to be related to the NF-κB signaling pathway. Taken together, our study provides evidence that PBM could be a potentially effective therapy for NP after SCI, CXCL10 and NF-kB signaling pathways might be critical factors in pain relief mediated by PBM after SCI.

Effect of post-extubation high-flow nasal cannula combined with respiratory training versus conventional oxygen therapy on postoperative pulmonary complications in patients after major abdominal surgery: protocol for a single-centre randomized controlled trial.

BACKGROUND: Nearly 234 million patients undergo surgery each year, and 1.3 million among them develop complications. Patients undergoing major upper abdominal surgery (operation time > 2 h) have a really high incidence of postoperative pulmonary complications (PPCs). The occurrence of PPCs seriously affects the outcomes of patients. High-flow nasal cannula (HFNC) is as effective as noninvasive ventilation (NIV) in preventing postoperative hypoxaemia and respiratory failure. Respiratory training using positive expiratory pressure (PEP) Acapella (Choice) has been shown to help patients with rapid recovery from postoperative atelectasis. However, no relevant randomized controlled studies have been conducted to clarify the effect of HFNC combined with respiratory training in the prevention of PPCs. This study aims to investigate whether the use of HFNC combined with respiratory training could reduce the incidence of PPCs within 7 days after major upper abdominal surgery compared to that with conventional oxygen therapy (COT). METHODS: This is a randomized controlled single-centre trial. A total of 328 patients who undergo major abdominal surgery will be included. Subjects who fulfil the eligible criteria will be randomly assigned into the combination treatment group (Group A) or COT group (Group B) after extubation. The interventions will begin within 30 min of extubation. Patients in Group A will receive HFNC for at least 48 h and respiratory training three times a day for at least 72 h. Patients in Group B will receive oxygen therapy through a nasal catheter or mask for at least 48 h. Our primary endpoint is the incidence of PPCs within 7 days, and the secondary outcome measures include 28-day mortality, reintubation rate, length of hospital stay, and all-cause mortality within 1 year. DISCUSSION: This trial would help provide evidence on the effectivity of applying HFNC combined with respiratory training for the prevention of PPCs in patients undergoing major upper abdominal surgery. The objective of this study is to determine the optimal treatment approach to improve the prognosis of patients undergoing surgery. TRIAL REGISTRATION: ChiCTR2100047146. Registered on 8 June 2021. Retrospectively registered.

Accelerating Gas Escape in Anion Exchange Membrane Water Electrolysis by Gas Diffusion Layers with Hierarchical Grid Gradients.

At high current densities, gas bubble escape is the critical factor affecting the mass transport and performance of the electrolyzer. For tight assembly water electrolysis technologies, the gas diffusion layer (GDL) between the catalyst layer (CL) and the flow field plate plays a critical role in gas bubble removal. Herein, we demonstrate that the electrolyzer's mass transport and performance can be significantly improved by simply manipulating the structure of the GDL. Combined with 3D printing technology, ordered nickel GDLs with straight-through pores and adjustable grid sizes are systematically studied. Using an in situ high-speed camera, the gas bubble releasing size and resident time have been observed and analyzed upon the change of the GDL architecture. The results show that a suitable grid size of the GDL can significantly accelerate mass transport by reducing the gas bubble size and the bubble resident time. An adhesive force measurement has further revealed the underlying mechanism. We then proposed and fabricated a novel hierarchical GDL, reaching a current density of 2 A/cm2 at a cell voltage of 1.95 V and 80 °C, one of the highest single-cell performances in pure-water-fed anion exchange membrane water electrolysis (AEMWE).

Smart Biomimetic Nanozymes for Precise Molecular Imaging: Application and Challenges.

New nanotechnologies for imaging molecules are widely being applied to visualize the expression of specific molecules (e.g., ions, biomarkers) for disease diagnosis. Among various nanoplatforms, nanozymes, which exhibit enzyme-like catalytic activities in vivo, have gained tremendously increasing attention in molecular imaging due to their unique properties such as diverse enzyme-mimicking activities, excellent biocompatibility, ease of surface tenability, and low cost. In addition, by integrating different nanoparticles with superparamagnetic, photoacoustic, fluorescence, and photothermal properties, the nanoenzymes are able to increase the imaging sensitivity and accuracy for better understanding the complexity and the biological process of disease. Moreover, these functions encourage the utilization of nanozymes as therapeutic agents to assist in treatment. In this review, we focus on the applications of nanozymes in molecular imaging and discuss the use of peroxidase (POD), oxidase (OXD), catalase (CAT), and superoxide dismutase (SOD) with different imaging modalities. Further, the applications of nanozymes for cancer treatment, bacterial infection, and inflammation image-guided therapy are discussed. Overall, this review aims to provide a complete reference for research in the interdisciplinary fields of nanotechnology and molecular imaging to promote the advancement and clinical translation of novel biomimetic nanozymes.