A novel approach for purifying food waste anaerobic digestate through bio-conditioning dewatering followed by activated sludge process: A case study.

Although anaerobic digestion is the mainstream technology for treating food waste (FW), the high pollutant concentration in the resultant food waste anaerobic digestate (FWAD) often poses challenges for the subsequent biochemical treatment such as activated sludge process. In this study, taking a typical FW treatment plant as an example, we analyzed the reasons behind the difficulties in treating FWAD and tested a novel process called as bio-conditioning dewatering followed by activated sludge process (BDAS) to purify FWAD. Results showed that high concentrations of suspended solids (SS) (16439 ± 475 mg/L), chemical oxygen demand (COD) (24642 ± 1301 mg/L), and ammonium nitrogen (NH4+-N) (2641 ± 52 mg/L) were main factors affecting the purification efficiency of FWAD by the conventional activated sludge process. By implementing bio-conditioning dewatering for solid-liquid separation, near 100% of SS and total phosphorus (TP), 90% of COD, 38% of total nitrogen (TN), and 37% of NH4+-N in the digestate could be effectively removed or recovered, consequently generating the transparent filtrate with relatively low pollution load and dry sludge cake (<60% of moisture content). Furthermore, after ammonia stripping and biochemical treatment, the effluent met the relevant discharge standards regulated by China, with the concentrations of COD, TN, NH4+-N, and TP ranging from 151 to 405, 10-56, 0.9-31, and 0.4-0.8 mg/L, respectively. This proposed BDAS approach exhibited stable performance and low operating costs, offering a promising solution to purify FWAD in practical engineering and simultaneously realize resource recovery.

Yangyinghuoxue decoction exerts a treatment effect on hepatic fibrosis by PI3K/AKT pathway in rat model: based on the network pharmacology and molecular docking.

BACKGROUND: Yangyinghuoxue decoction (YYHXD) is a Traditional Chinese medicine (TCM) compound with satisfactory clinical efficacy in the treatment of hepatic fibrosis (HF). However, the pharmacological molecular mechanisms of YYHXD in the treatment of hepatic fibrosis have not yet been clarified. OBJECTIVE: To determine the pharmacological mechanisms of YYHXD for the treatment of hepatic fibrosis via network pharmacology analysis combined with experimental verification. METHODS: First, the bioactive ingredients and potential targets of YYHXD and HF-related targets were retrieved from the online databases and literatures. Next, the "herb-ingredient-target-disease" network and PPI network were constructed for topological analyses and key active compounds and targets screening. Enrichment analyses were performed to identify the critical biological processes and signaling pathways. Then, the molecular docking experiment was performed to initially validate the network pharmacology prediction results. Finally, the antifibrotic effect and pharmacological mechanisms of YYHXD were investigated in CCl4 induced liver fibrosis in rats. RESULTS: In total, 141 active compounds in YYHXD, 637 YYHXD-related targets and 1598 liver fibrosis-related targets were identified. Among them, 69 overlapped targets were finally obtained. Network analysis screened 5 critical bioactive components and 34 key targets. Functional enrichment analysis indicated that YYHXD obviously influenced biological processes such as oxidative stress, cellular inflammation and hepatocyte apoptosis and signaling pathways such as PI3K-Akt, Apoptosis, and JAK-STAT in the treatment of HF. The molecular docking results suggested that the YYHXD may have a direct impact on the PI3K-Akt signaling pathway. Further, in vivo experiment indicated that YYHXD treatment not only reduced liver injury and protected liver function, but also decrease the apoptosis of hepatic parenchyma cells, reducing inflammatory and attenuating oxidative stress. Moreover, YYHXD significantly attenuated the upregulation of target proteins enriched in PI3K signaling pathway, including P-PI3K, P-Akt1, HSP90, MYC, p53. CONCLUSIONS: The mechanisms of YYHXD against liver fibrosis were involved in multiple ingredients, multiple targets and multiple signaling pathways. The PI3K/Akt pathway could be the most important pharmacological mechanism of YYHXD therapy for liver fibrosis.

Brain Structural Connectivity Guided Vision Transformers for Identification of Functional Connectivity Characteristics in Preterm Neonates.

Preterm birth is the leading cause of death in children under five years old, and is associated with a wide sequence of complications in both short and long term. In view of rapid neurodevelopment during the neonatal period, preterm neonates may exhibit considerable functional alterations compared to term ones. However, the identified functional alterations in previous studies merely achieve moderate classification performance, while more accurate functional characteristics with satisfying discrimination ability for better diagnosis and therapeutic treatment is underexplored. To address this problem, we propose a novel brain structural connectivity (SC) guided Vision Transformer (SCG-ViT) to identify functional connectivity (FC) differences among three neonatal groups: preterm, preterm with early postnatal experience, and term. Particularly, inspired by the neuroscience-derived information, a novel patch token of SC/FC matrix is defined, and the SC matrix is then adopted as an effective mask into the ViT model to screen out input FC patch embeddings with weaker SC, and to focus on stronger ones for better classification and identification of FC differences among the three groups. The experimental results on multi-modal MRI data of 437 neonatal brains from publicly released Developing Human Connectome Project (dHCP) demonstrate that SCG-ViT achieves superior classification ability compared to baseline models, and successfully identifies holistically different FC patterns among the three groups. Moreover, these different FCs are significantly correlated with the differential gene expressions of the three groups. In summary, SCG-ViT provides a powerfully brain-guided pipeline of adopting large-scale and data-intensive deep learning models for medical imaging-based diagnosis.

Proteins extracted from pearl oyster (Pinctada martensii) with efficient accelerated wound healing in vitro through promoting cell proliferation, migration, and collagen formation.

Ethnopharmacological relevance: Pearl oyster (Pinctada martensii) is used in Chinese traditional medicine use in photoprotective, anti-inflammatory, and wound treatment.Aim of the study: This study explored whether the mucus protein of Pearl oyster (protein of Pinctada martensii, PMP) affects human skin fibroblast (HSF) proliferation, migration, collagen-related gene expression related to collagen formation, and in vivo healing effects. Materials and methods: The PMP component was analyzed by LC-MS/MS. The cell viability was evaluated using a CCK-8 kit. The expression genes were measured by reverse transcription polymerase chain reaction. A full-thickness excisional wounding model in Sprague-Dawley (SD) rats was used to test the repairing effect of PMP in vivo, and Hematoxylin-Eosin (H&E) and Masson's Trichrome staining were applied to evaluate skin structure. Results: The components of PMP were identified using LC-MS/MS proteomics, and a total of 3023 proteins were detected. The results of PMP-treated HSF showed that PMP effectively promoted cell proliferation by 1.6-fold and cell migration by 1.5-fold at a concentration of 1 mg/mL. Additionally, PMP treatment up-regulated the expression levels of collagen-related genes COL1A1, COL3A1, and MMP-1 in fibroblasts. Furthermore, PMP was applied in the therapy of full-thickness excisional wounds in rats. The results demonstrated that PMP significantly accelerated wound healing time, resulted in the recovery of dermal and epithelial thickness, and stimulated collagen regeneration. The regenerated skin closely resembled the structure of normal skin. Conclusions: These findings provide solid evidence supporting the potential of PMP as a promising candidate for the treatment of skin wounds.

Feathery Tellurium-Selenium Heterostructural Nanoadjuvant for the Synergistic Treatment of Bacterial Infections.

Antibacterial nanoagents with well-controlled structures are greatly desired to address the challenges of bacterial infections. In this study, a featherlike tellurium-selenium heterostructural nanoadjuvant (TeSe HNDs) was created. TeSe HNDs produced 1O2 and had high photothermal conversion efficiency when stimulated with 808 nm near-infrared (NIR) light. To create a synergistic treatment system (TeSe-ICG) with better photothermal and photodynamic capabilities, the photosensitizer indocyanine green (ICG) was then added. With a bactericidal rate of more than 99%, the NIR-mediated TeSe-ICG demonstrated an efficient bactericidal action against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). In addition, TeSe-ICG was also effective in treating wound infections and could effectively promote wound healing without obvious toxic side effects. In conclusion, TeSe-ICG is expected to be a good candidate for the treatment of bacterial infections.

Dapagliflozin Attenuates NLRP3/Caspase-1 Signaling Pathway-Mediated Pyroptosis of Vascular Smooth Muscle Cells by Downregulating CTSB.

Background: Atherosclerosis is a chronic inflammatory disease. Pyroptosis triggers and amplifies the inflammatory response and plays an important role in atherosclerosis. Cathepsin B (CTSB) can promote atherosclerosis and activate NOD-like receptor protein 3 (NLRP3) to mediate pyroptosis. Dapagliflozin (DAPA) can inhibit cell pyroptosis to improve atherosclerosis. This study aimed to explore the effect of DAPA on oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis of vascular smooth muscle cells (VSMCs) and its underlying mechanism. Objective: We aimed to investigate the effect of DAPA on ox-LDL-induced pyroptosis of VSMCs in mice and its underlying mechanism. Methods: VSMCs were transfected with CTSB-overexpressing and -silencing lentiviral vectors. VSMCs were treated with different concentrations of ox-LDL (0, 50, 100 and 150 µg/ml ). Then, Hoechst 33342/PI double staining, interleukin (IL)-1ß and lactate dehydrogenase (LDH) release assay were used to detect cell pyroptosis. Western blotting was used to detect pyroptosis indicators protein, based on which the appropriate concentration of ox-LDL was selected. After VSMCs were treated with different concentrations of DAPA (0.1 µM, 1.0 µM, 5.0 µM, 10 µM, 25 µM and 50 µM), the proliferative activity of VSMCs was detected using Cell Counting Kit-8 (CCK8) assay. After VSMCs were pretreated with different DAPA concentrations (0.1 µM, 1.0 µM, 5.0 µM and 10 µM) for 24 hours and then treated with 150 µg/mL ox-LDL for 24 hours, the effects of different concentrations of DAPA on pyroptosis of VSMCs were detected, based on which the appropriate DAPA concentration was selected. After lentivirus transfected VSMCs were treated with 150 µg/mL ox-LDL for 24 hours, the effects of overexpression and silencing of CTSB in pyroptosis were observed. On the basis of DAPA (0.1 µM)- and ox-LDL(150 µg/mL)-treated VSMCs, overexpression and silencing of CTSB were used to observe the effects of DAPA and CTSB on ox-LDL-mediated VSMCs pyroptosis. Results: (1) VSMCs stably transfected with CTSB-overexpressing and -silencing lentiviruses were obtained; 150 µg/mL was the optimal concentration of ox-LDL for inducing pyroptosis of VSMCs, and 0.1 µM was the optimal concentration of DAPA for ameliorating pyroptosis of VSMCs. (2) Ox-LDL-induced pyroptosis of VSMCs was worsened by CTSB overexpression but suppressed by CTSB silencing. (3) DAPA attenuated ox-LDL-induced pyroptosis of VSMCs through downregulating CTSB and NLRP3. (4) Overexpression of CTSB based on DAPA intervention aggravated ox-LDL-induced pyroptosis of VSMCs. Conclusion: DAPA attenuates NLRP3/caspase-1 pathway-mediated pyroptosis of VSMCs through downregulating CTSB.

System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from Duhuo Jisheng decoction on osteoarthritis in rats.

ETHNOPHARMACOLOGY RELEVANCE: Duhuo Jisheng decoction is a traditional Chinese formula that has been widely used in clinical practice to treat osteoarthritis, which has the effects of removing invaded cold and dampness, relieving joint pain. However, it is difficult to determine the effective substances and mechanisms due to assorted herbs and components, and further research is needed. AIM OF THE STUDY: This study was designed to explore and verify the mechanism and targets of DHJSD in the treatment of OA via network analysis and experiments. METHOD: In this study, the active ingredients of DHJSD were qualitatively analyzed by UPLC-QDA. Network analysis was used to identify common targets and pathways. Next, we explored the therapeutic mechanism of DHJSD through a rat model of knee osteoarthritis. HE staining was used to judge the establishment of the animal model. ELISA and Western blotting were used to verify the expression of key pathway proteins. CONCLUSION: In this study, seventeen chemical constituents in DHJSD were identified. According to the network analysis, we obtained the potential associated pathways of action. Then, molecular docking and SPR experiments showed that the sixteen identified components had high binding energies to IL-6. HE staining showed that the high-dose group of DHJSD had an obvious therapeutic effect on model rats. Compared with the model group, the levels of IL-1ß, TNF-α, IL-6, MMP3, MMP13, ADAMTS4 and ADAMTS5 in serum and the expression of STAT3 and p-STAT3 protein in administration groups were significantly decreased. This result indicated that the IL-6/STAT3 signaling pathway was one of the important pathways regulated by DHJSD to improve OA.

Overexpression of ClWRKY48 from Cunninghamia lanceolata improves Arabidopsis phosphate uptake.

MAIN CONCLUSION: Our findings suggested that ClWRKY48 promoted the expression level of Arabidopsis phosphate transporter genes, enhanced phosphate uptake, and delayed the transition from the vegetative stage to the reproductive phase in Arabidopsis. Phosphorus (P) is an essential mineral for plants that influences their growth and development. ClWRKY48, one of the most highly expressed genes in the leaf, was identified by RT-PCR from Chinese fir [Cunninghamia lanceolata (Lamb.) Hook] (C. lanceolata). Furthermore, when treating C. lanceolata with increasing phosphate (Pi) concentration, the expression level of ClWRKY48 rose in leaves, the trends followed the increasing phosphate concentration treatment. ClWRKY48 is a transcription factor in C. lanceolata, according to the results of a yeast one hybridization experiment. Based on subcellular localization studies, ClWRKY48 is a nuclear-localized protein. Under Pi deficiency conditions, the phosphorus concentration of ClWRKY48 overexpressing Arabidopsis increased by 43.2-51.1% compared to the wild-type. Moreover, under Pi limiting conditions, the phosphate transporter genes AtPHT1;1 (Arabidopsis Phosphate transporter 1;1), AtPHT1;4, and AtPHO1 (Arabidopsis PHOSPHATE 1) were expressed 2.1-2.5, 2.2-2.7, and 6.7-7.3-fold greater than the wild-type in ClWRKY48 transgenic Arabidopsis, respectively. Under Pi-sufficient conditions, the phosphorus concentration and phosphate transporter genes of ClWRKY48 overexpression in Arabidopsis are not significantly different from the wild type. These findings indicated that ClWRKY48 increased phosphate absorption in transgenic Arabidopsis. Furthermore, compared to the wild type, the ClWRKY48 transgenic Arabidopsis not only had a delayed flowering time characteristic but also had lower expression of flowering-related genes AtFT (FLOWERING LOCUS T), AtFUL (FRUITFUL), and AtTSF (TWIN SISTER OF FT). Our findings show that ClWRKY48 enhances phosphate absorption and slows the transition from the vegetative to the reproductive stage in ClWRKY48 transgenic Arabidopsis.

Green tea consumption and the risk of coronary heart disease: A systematic review and meta-analysis of cohort studies.

BACKGROUND AND AIMS: Conflicting evidence exists regarding the association between green tea consumption and the risk of coronary heart disease (CHD). We performed a meta-analysis to determine whether an association exists between them in cohort studies. METHODS AND RESULTS: We searched the PubMed and EMBASE databases for studies conducted until September 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence intervals (CIs) for the association were included. Study-specific risk estimates were combined using a random-effects model. A total of seven studies, with 9211 CHD cases among 772,922 participants, were included. We observed a nonlinear association between green tea consumption and the risk of CHD (P for nonlinearity = 0.0009). Compared with nonconsumers, the RRs (95% CI) of CHD across levels of green tea consumption were 0.89 (0.83, 0.96) for 1 cup/day (1 cup = 300 ml), 0.84 (0.77, 0.93) for 2 cups/day, 0.85 (0.77, 0.92) for 3 cups/day, 0.88 (0.81, 0.96) for 4 cups/day, and 0.92 (0.82, 1.04) for 5 cups/day. CONCLUSIONS: This updated meta-analysis of studies from East Asia suggests that green tea consumption may be associated with a reduced risk of CHD, especially among those with low-to-moderate consumption. Additional cohorts are still needed before we could draw a definitive conclusion. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022357687.

A new model for the treatment of type 2 diabetes mellitus based on rhythm regulations under the framework of psychosomatic medicine: a real-world study.

We aimed to explore a new treatment model for type 2 diabetes mellitus (DM) based on rhythm regulation under the framework of psychosomatic medicine. Using psychotropics as rhythm regulators, 178 patients with DM were evaluated and divided into three groups: the antidiabetic treatment group (AT group), psychotropic treatment group (PT group), and combined antidiabetic + psychotropic treatment group (combined group), for a course of 16 weeks. The West China Psychiatry Association (WCPA) Somatic Symptom Classification Scale (SSCS) was used to evaluate each patient. The levels of hormones in the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid axes and of blood glucose and glycosylated hemoglobin (HbA1c) were evaluated both before and after treatment. After the treatment, the blood glucose and HbA1c levels in all three groups were lower than those at baseline. Furthermore, the incidence of the abnormal HPA axis in the PT group was significantly decreased (P = 0.003), while the incidence of the abnormal HPA axis in the combined group was 0.0%. The five factor scores of the SSCS in the PT and combined groups after treatment were both significantly low (P < 0.01). Both the incidence of abnormal neuroendocrine axes and SSCS scores in the AT group showed no significant difference before and after treatment. "Blood glucose control + rhythm regulation" should be considered as optimised treatment goals for DM. Moreover, some psychotropics could be used as biorhythm regulators, which have good potential value for clinical application.Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Reinterpretation of mechanism and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis. The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Green tea consumption and the risk of stroke: A systematic review and meta-analysis of cohort studies.

OBJECTIVES: Epidemiologic studies are inconsistent regarding the association between green tea consumption and the risk of stroke. We performed a meta-analysis to determine whether an association exists between them in cohort studies. METHODS: We searched the PubMed and Embase databases for studies conducted from 1966 through September 2022. Prospective cohort studies that provided relative risk (RR) estimates with 95% confidence interval (CI)s for the association were included. Study-specific risk estimates were combined by using a random-effects model. RESULTS: A total of five studies, with 11 421 stroke cases among 645 393 participants, were included in the meta-analysis. The summary RR indicated a significant association between highest green tea consumption and reduced risk of stroke (summary RR: 0.74; 95% CI, 0.66-0.83). In the dose-response analysis, we observed a nonlinear association between green tea consumption and the risk of stroke (P for nonlinearity = 0.0000). Compared with non-consumers, the RRs (95% CI) of stroke across levels of green tea consumption were 0.91 (0.89-0.94) for 150 mL/d, 0.84 (0.80-0.89) for 300 mL/d, 0.79 (0.74-0.84) for 500 mL/d, 0.77 (0.72-0.82) for 900 mL/d, and 0.84 (0.77-0.91) for 1500 mL/d. CONCLUSIONS: This meta-analysis suggests that green tea consumption is inversely associated with the risk of stroke, especially among those with moderate consumption. Our results support recommendations for green tea consumption to the primary prevention of stroke.

FNDC5/PPARa Pathway Alleviates THP-1-derived Macrophage Pyroptosis and Its Mechanism.

Context: Atherosclerosis (AS) is a chronic inflammatory disease. Pyroptosis is a newly discovered, pro-inflammatory cell death that can trigger and amplify the occurrence and progression of AS. Researchers are still uncertain about the anti-atherosclerotic mechanism of "fibronectin type III domain-containing protein 5" (FNDC5). Objective: The study aimed to investigate the ability of FNDC5-mediated, "peroxisome proliferator activated receptor alpha" (PPARa) to inhibit oxidized low-density lipoprotein (ox-LDL)-induced, THP-1-derived macrophage pyroptosis and to determine a potential molecular mechanism at the cellular level. Design: The research team performed a laboratory study. Setting: The study took place in the Department of Cardiovascular Medicine at the Affiliated Hospital of Guzhou Medical University at the Medical Research Institute at Guizhou Medical University in Guiyang, Guizhou, China. Outcome Measures: The research team: (1) constructed and stably transfected FNDC5 gene-overexpressing and FNDC5 gene-silencing lentiviral vectors into THP-1 cells; (2) observed the cell morphology under an inverted fluorescence microscope and screened the stably transfected THP-1 cells with puromycin; (3) verified the transfection efficiency using quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot; (4) used phorbol to induce THP-1 cells into macrophages; (5) cultured the THP-1-derived macrophages with different concentrations of ox-LDL-25, 50, 75, and 100 µg/ml-for 24 h; (6) performed Hoechst 33342/ propidium iodide (PI) double staining and examined lactate dehydrogenase (LDH) and interleukin-1 beta (IL-1ß) activity to determine the effects of ox-LDL on THP-1-derived macrophage pyroptosis; (7) selected the optimal ox-LDL concentration; (8) divided the THP-1-derived macrophages into seven groups: NC group (no ox-LDL intervention), ox-LDL group, PBS group, Mock1 group, Ad-FNDC5 group, Mock2 group, and Sh-FNDC5 group; (9) examined the expressions of functional proteins and the pyroptosis of THP-1-derived macrophages, including FNDC5, PPARa, and "nuclear factor kappa-light chain enhancer of activated B cells P65" (NF-κB P65), and those related to the pyroptosis pathway, using Western Blot and Hoechst 33342/PI double staining, respectively; (10) treated the THP-1-derived macrophages with FNDC5 expression with GW6471, a specific PPARα antagonist; (11) determined the expressions of functional proteins and the pyroptosis of THP-1-derived macrophages, including FNDC5, PPARa, and NF-κB P65, and those related to the pyroptosis pathway, using Western Blot and Hoechst 33342/PI double staining and detection of the LDH and IL-1ß activity, respectively. Results: With the stably transfected THP-1 cells with FNDC5 overexpression or silencing the ox-LDL-induced, THP-1-derived, macrophage pyroptosis occurred in a concentration-dependent manner. Compared with the ox-LDL, phosphate buffered saline (PBS), Mock1, and Mock2 groups, the Ad-FNDC5 group had a significant increase in expression of FNDC5 and of peroxisome proliferator activated receptor alpha (PPARa) proteins (P < .05). The "nuclear factor kappa-light chain enhancer of activated B cells P65: (NF-κB P65), NOD-like receptor thermal protein domain associated protein 3, (NLRP3), Caspase-1, gasdermin D (GSDMD, IL-1ß and IL-18 protein expressions, percentage of PI-positive cells, LDH activity, and IL-1ß activity decreased significantly (P < .05); the results in the Sh-FNDC5 group were opposite to those in the Ad-FNDC5 group. 3. Intervention with GW6471 (PPARa antagonist) in the stably transfected THP-1-derived macrophages with FNDC5 overexpression abolished the protective effect of FNDC5 against ox-LDL-induced THP-1-derived macrophage pyroptosis. Conclusions: Irisin/PPARa inhibited THP-1-derived macrophage pyroptosis and inflammation and delayed AS by inhibiting the NF-κB/NLRP3 pathway.

Re-interpretation of the mechanism of type 2 diabetes mellitus based on a framework of psychosomatic medicine: a real-world study.

OBJECTIVE: Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. METHODS: In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes were measured. RESULTS: Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the 'disease group, the BD + pre-DM group as the 'mixed period group', and the pre-DM group as the 'pre-disease group'. The conscientiousness factor scores of the NEO-FFI in the 'disease group' were higher than the norm but lower than the norm in the 'pre-disease group'. The scores of neurotic factors in the 'pre-disease' and 'mixed period' groups were both significantly higher than that in the 'disease group' (corrected p < 0.001). The incidences of the abnormal HPA axis decreased gradually from the 'pre-disease group' to the 'mixed period group' then to the 'disease group', while those of the HPT axis slightly increased at first and then significantly decreased. The overall prediction rate of the multiple logistic regression model was 92.7%. CONCLUSION: This study suggests that progression of pre-diabetes to DM is a continuous process from local abnormalities to rhythm disorder of glucose metabolism. This understanding can be applied to the whole course management and early intervention of DM and to the future development of optimised treatment based on rhythm regulation. TRIAL REGISTRATION: Clinical trial registration number: ChiCTR1800019064. Name of trial registration: Identify and the optimization of treatment for non-infectious chronic diseases under the "stress-dysrhythmia" theory hypothesis (Registration date: 24/10/2018). The full trial protocol can be accessed at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ).

Biomimetic Yolk-Shell Nanocatalysts for Activatable Dual-Modal-Image-Guided Triple-Augmented Chemodynamic Therapy of Cancer.

Fenton reaction-based chemodynamic therapy (CDT), which applies metal ions to convert less active hydrogen peroxide (H2O2) into more harmful hydroxyl peroxide (·OH) for tumor treatment, has attracted increasing interest recently. However, the CDT is substantially hindered by glutathione (GSH) scavenging effect on ·OH, low intracellular H2O2 level, and low reaction rate, resulting in unsatisfactory efficacy. Here, a cancer cell membrane (CM)-camouflaged Au nanorod core/mesoporous MnO2 shell yolk-shell nanocatalyst embedded with glucose oxidase (GOD) and Dox (denoted as AMGDC) is constructed for synergistic triple-augmented CDT and chemotherapy of tumor under MRI/PAI guidance. Benefiting from the homologous adhesion and immune escaping property of the cancer CM, the nanocatalysts can target tumor and gradually accumulate in tumor site. For triple-augmented CDT, first, the MnO2 shell reacts with intratumoral GSH to generate Mn2+ and glutathione disulfide, which achieves Fenton-like ion delivery and weakening of GSH-mediated scavenging effect, leading to GSH depletion-enhanced CDT. Second, the intratumoral glucose can be oxidized to H2O2 and gluconic acid by GOD, achieving supplementary H2O2-enhanced CDT. Next, the AuNRs absorbing in NIR-II elevate the local tumor temperature upon NIR-II laser irradiation, achieving photothermal-enhanced CDT. Dox is rapidly released for adjuvant chemotherapy due to responsive degradation of MnO2 shell. Moreover, GSH-activated PAI/MRI can be used to monitor CDT process. This study provides a great paradigm for enhancing CDT-mediated antitumor efficacy.

The effect of acupuncture on oxidative stress: A systematic review and meta-analysis of animal models.

INTRODUCTION: Oxidative stress is involved in the occurrence and development of multiple diseases. Acupuncture shows an excellent clinical efficacy in practical application but its mechanism remains unclear. This systematic review and meta-analysis was aimed at assessing the effect of acupuncture on oxidative stress in animal models. METHODS: PubMed, Embase, and Web of Science database were retrieved for randomized controlled trials about acupuncture on oxidative stress in animal models from inception to August 2021. Two reviewers independently screened and extracted articles according to inclusion and exclusion criteria. We used the mean difference (MD)/standardized mean difference (SMD) to perform an effect size analysis and selected fixed-effect or random-effect models to pool the data, depending on a 95% confidence interval (CI). RESULTS: A total of 12 studies comprising 125 samples were included in the quantitative meta-analysis. Compared with sham acupuncture, acupuncture (manual acupuncture, electropuncture, and laser acupuncture) reduced the level of malondialdehyde (SMD, -3.03; CI, -4.40, -1.65; p < 0.00001) and increased the levels of superoxide dismutase (SMD, 3.39; CI, 1.99, 4.79; p < 0.00001), glutathione peroxidase (SMD, 2.21; CI, 1.10, 3.32; p < 0.00001), and catalase (SMD, 2.80; CI, 0.57, 5.03; p = 0.01). CONCLUSION: This meta-analysis indicated that acupuncture can regulate oxidative stress by lowering the lipid peroxidation and activating the antioxidant enzyme system. In consideration of heterogeneity between studies, future studies should be performed by complying with strict standards and increasing sample size in animal experiments to reduce bias.

Effects of dietary supplement with a Chinese herbal mixture on growth performance, antioxidant capacity, and gut microbiota in weaned pigs.

Weaning stress decreases the growth performance of piglets and is one of the main concerns of pig industries. Traditional Chinese herbal medicines have been used to reduce the adverse effects of weaning stress as both nutritional supplements and antibiotic substitutes. This study aimed to evaluate the effects of a Chinese herbal mixture (Kangtaile, which contained Paeonia lactiflora, licorice, dandelion, and tea polyphenols) on the growth performances, immune response, antioxidant capacity, and intestinal microbiota of weaned pigs. A total of 400 weaned pigs [Duroc × (Landrace × Yorkshire)] were randomly allocated into one of four treatments: the CON group, fed with basic diet; the HM1 group, fed with basal diet supplemented with 0.5 g herbal mixture/kg diet; the HM2 group, fed with basal diet supplemented with 1.0 g herbal mixture/kg diet; or the HM3 group, fed with basal diet supplemented with 1.5 g herbal mixture/kg diet. The results revealed that dietary supplementation with the herbal mixture for 28 days improved average daily gain and feed conversion ratio, while decreased the diarrhea rate of weaned pigs. Moreover, dietary supple-mentation with the herbal mixture improved the antioxidant capacity through increasing the activity of catalase (CAT) and the total antioxidant capacity (T-AOC) level, while decreasing the concentration of malondialdehyde (MDA) in the serum. Pigs supplemented with herbal mixture presented an increased serum immunoglobulin (Ig)M level on day 14 compared with control pigs. The herbal mixture altered the composition of intestinal microbiota by influencing the relative abundances of Firmicutes and Bacteroidetes at the phylum level. The relative abundances of the Firmicutes and Bacteroidetes were significantly related to the body weight gain of pigs. In conclusion, supplementation of herbal mixture to the diet improved growth performance, immunity, and antioxidant capacity and modified the composition of intestinal microbiota in weaning pigs. This study provided new insights into the nutritional regulation effects of the herbal mixtures on weaned pigs.

The Role and Mechanisms of Traditional Chinese Medicine for Airway Inflammation and Remodeling in Asthma: Overview and Progress.

Asthma as an individual disease has blighted human health for thousands of years and is still a vital global health challenge at present. Though getting much progress in the utilization of antibiotics, mucolytics, and especially the combination of inhaled corticosteroids (ICS) and long-acting ß-agonists (LABA), we are confused about the management of asthmatic airway inflammation and remodeling, which directly threatens the quality of life for chronic patients. The blind addition of ICS will not benefit the remission of cough, wheeze, or sputum, but to increase the risk of side effects. Thus, it is necessary to explore an effective therapy to modulate asthmatic inflammation and airway remodeling. Traditional Chinese Medicine (TCM) has justified its anti-asthma effect in clinical practice but its underlying mechanism and specific role in asthma are still unknown. Some animal studies demonstrated that the classic formula, direct exacts, and natural compounds isolated from TCM could significantly alleviate airway structural alterations and exhibit the anti-inflammatory effects. By investigating these findings and data, we will discuss the possible pathomechanism underlined airway inflammation and remodeling in asthma and the unique role of TCM in the treatment of asthma through regulating different signaling pathways.

Switching the NIR upconversion of nanoparticles for the orthogonal activation of photoacoustic imaging and phototherapy.

Phototheranostics based on upconversion nanoparticles (UCNPs) offer the integration of imaging diagnostics and phototherapeutics. However, the programmable control of the photoactivation of imaging and therapy with minimum side effects is challenging due to the lack of ideal switchable UCNPs agents. Here we demonstrate a facile strategy to switch the near infrared emission at 800 nm from rationally designed UCNPs by modulating the irradiation laser into pulse output. We further synthesize a theranostic nanoagent by combining with a photosensitizer and a photoabsorbing agent assembled on the UCNPs. The orthogonal activation of in vivo photoacoustic imaging and photodynamic therapy can be achieved by altering the excitation modes from pulse to continuous-wave output upon a single 980 nm laser. No obvious harmful effects during photoexcitation was identified, suggesting their use for long-term imaging-guidance and phototherapy. This work provides an approach to the orthogonal activation of imaging diagnostics and photodynamic therapeutics.

Michael acceptor-dependent pro-oxidative intervention against angiogenesis by [6]-dehydroshogaol, a pungent constituent of ginger.

Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.

Soil nutrient deficiency decreases the postharvest quality-related metabolite contents of tea (Camellia sinensis (L.) Kuntze) leaves.

The long-term cultivation of tea plants without fertilization can severely decrease yield, but it remains unclear whether this soil nutrient deficiency affects tea quality. In this study, tea plants (Camellia sinensis (L.) Kuntze) cultivated in unfertilized soil for 11 years were analyzed. The soil nutrient deficiency down-regulated protochlorophyllide oxidoreductase-encoding gene expression, which adversely affected chlorophyll biosynthesis, ultimately leading to leaf etiolation. Because of decreased synthesis and increased degradation in response to nutrient deficiency, l-theanine content decreased to 11.4% of the control level, which increased the phenol-ammonia ratio and decreased taste quality. Soil nutrient deficiency also decreased the abundance of many aroma compounds (e.g., green leaf volatile, linalool and its oxides, and methyl salicylate). Thus, nutrient deficiency adversely influences tea color, taste, and aroma. This study provides researchers and tea growers with important information regarding the effects of soil nutrient deficiency on tea quality and the rational fertilization of tea gardens.