Effects of electroacupuncture on Sirt3/NLRP3/GSDMD signaling pathway in the substantia nigra of midbrain of rats with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å¤§é¼ ä¸­è„‘é»‘è´¨Sirt3/NLRP3/GSDMD信号通路的影响.

OBJECTIVES: To observe the effects on tyrosine hydroxylase (TH), α-synaptic nucleoprotein (α-syn), sirtuin 3 (Sirt3), NOD-like receptor 3 (NLRP3) and gasdermin-D (GSDMD) in the substantia nigra of midbrain after electroacupuncture (EA) at "Fengfu"(GV16), "Taichong" (LR3) and "Zusanli" (ST36) in rats of Parkinson's disease (PD), so as to explore the mechanism of EA in treatment of PD. METHODS: SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The PD model was established by injecting rotenone into the neck and back, lasting 28 days. In the EA group, EA was applied to GV16, LR3 and ST36, 30 min each time, once daily, consecutively for 28 days. The open-field test was adopted to detect the total distance of autonomic movement of rats, and the pole climbing test was used to detect the body coordination ability of rats. In the substania nigra of midbrain, the positive expression of TH was determined using immunohistochemistry, the mRNA expression levels of α - syn, Sirt3, NLRP3 and GSDMD were detected by quantitative real-time fluorescence PCR, and the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and cysteinyl aspartate specific proteinase (Caspase)-1 were detected by Western blot. RESULTS: Compared with the control group, the total distance of autonomous movement was decreased (P<0.01) in the model group, and the score of pole climbing experiment was increased (P<0.01)；in the midbrain substantia nigra the positive expression of TH was decreased (P<0.01)；the mRNA expression level of Sirt3 was decreased (P<0.01), and those of α-syn, NLRP3 and GSDMD were increased (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 were increased (P<0.01). When compared with the model group, the total distance of autonomous movement in open field experiment was increased (P<0.01) in the EA group and the score of pole climbing experiment was lower (P<0.05)；in the midbrain substantia nigra the positive expression of TH was increased (P<0.01)；the mRNA expression level of Sirt3 in the midbrain substantia nigra was increased (P<0.01), and those of α-syn, NLRP3 and GSDMD were reduced (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 decreased (P<0.01, P<0.05). CONCLUSIONS: EA at "GV16" "LR3" and "ST36" can repair the neuronal injury, clear the abnormal accumulation of α-syn in the substania nigra of midbrain, and ameliorate mitochondrial damage in PD rats, which may be obtained by regulating Sirt3/NLRP3/GSDMD signaling pathway, so as to delay the occurrence and development of Parkinson's disease.

Sustained oxidation of Tea-Fe(III)/H2O2 simultaneously achieves sludge reduction and carbamazepine removal: The crucial role of EPS regulation.

Establishing an economic and sustained Fenton oxidation system to enhance sludge dewaterability and carbamazepine (CBZ) removal rate is a crucial path to simultaneously achieve sludge reduction and harmless. Leveraging the principles akin to "tea making", we harnessed tea waste to continually release tea polyphenols (TP), thus effectively maintaining high level of oxidation efficiency through the sustained Fenton reaction. The results illustrated that the incorporation of tea waste yielded more favorable outcomes in terms of water content reduction and CBZ removal compared to direct TP addition within the Fe(III)/hydrogen peroxide (H2O2) system. Concomitantly, this process mainly generated hydroxyl radical (•OH) via three oxidation pathways, effectively altering the properties of extracellular polymeric substances (EPS) and promoting the degradation of CBZ from the sludge mixture. The interval addition of Fe(III) and H2O2 heightened extracellular oxidation efficacy, promoting the desorption and removal of CBZ. The degradation of EPS prompted the transformation of bound water to free water, while the formation of larger channels drove the discharge of water. This work achieved the concept of treating waste with waste through using tea waste to treat sludge, meanwhile, can provide ideas for subsequent sludge harmless disposal.

Effects of electroacupuncture on mitophagy mediated by SIRT3/PINK1/Parkin pathway in Parkinson's disease mice. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å°é¼ SIRT3/PINK1/Parkin通路介导的线粒体自噬的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Fengfu"(GV16), "Taichong"(LR3), and "Zusanli"(ST36) on mitophagy mediated by silencing regulatory protein 3 (SIRT3)/ PTEN induced putative kinase 1 (PINK1)/PARK2 gene coding protein (Parkin) in the midbrain substantia nigra of Parkinson's disease (PD) mice, and to explore the potential mechanisms of EA in treating PD. METHODS: C57BL/6 mice were randomly divided into the control, model, EA, and sham EA groups, with 12 mice in each group. The PD mouse model was established by intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). The EA group received EA stimulation at GV16, LR3 and ST36, while the sham EA group received shallow needling 1 mm away from the above acupoints without electrical stimulation. The motor ability of mice in each group was evaluated using an open field experiment. Immunohistochemistry was used to detect the expression of tyrosine hydroxylase (TH) and α-synuclein (α-syn) in the substantia nigra of mice. The ultrastructure of neurons in substantia nigra was observed by transmission electron microscope (TEM). Immunofluorescence was used to detect the expression of the autophagy marker autophagy-associated protein light chain 3 (LC3). The expression levels of TH, α-syn, SIRT3, PINK1, Parkin, P62, Beclin-1, LC3Ⅱ mRNA and protein were detected by PCR and Western blot. RESULTS: Compared with the control group, mice in the model group showed a decrease in the total exercise distance, time, movement speed and times of crossing central region (P<0.01)；the positive expressions of TH and LC3 were decreased (P<0.01), while the positive expression of α-syn increased (P<0.01), accompanied by mitochondrial swelling, mitochondrial cristae fragmentation and decrease, and decreased lysosome count；the expression levels of TH, SIRT3, PINK1, Parkin, Beclin-1, and LC3Ⅱ mRNA and protein in the midbrain substantia nigra were decreased (P<0.01), while the expression levels of α-syn and P62 mRNA and protein were increased (P<0.01, P<0.05). Compared with the model group, the mice in EA group showed a significant increase in the total exercise distance, time, movement speed and times of crossing central region (P<0.01, P<0.05)；the positive expressions of TH and LC3 were increased (P<0.01, P<0.05), while the positive expression of α-syn was decreased (P<0.01), accompanied by an increase in mitochondrial count, appearance of autophagic va-cuoles, and a decrease in swelling, the expression levels of TH, SIRT3, PINK1, Parkin, Beclin-1 and LC3Ⅱ mRNA and protein in the midbrain substantia nigra were increased (P<0.01, P<0.05), while the mRNA and protein expression levels of α-syn and P62 were decreased (P<0.01)；the sham EA group showed an increase in the total exercise distance and time(P<0.05), with an increase in the positive expression of TH (P<0.05) and a decrease in the positive expression of α-syn (P<0.05)；some mitochondria exhibited swelling, and no autophagic vacuoles were observed；the protein expression levels of TH, SIRT3, Parkin and LC3Ⅱ were increased (P<0.01, P<0.05), and the expression levels of P62 mRNA, α-syn mRNA and protein were decreased (P<0.01, P<0.05), and LC3Ⅱ mRNA expression was increased (P<0.05). In comparison to the sham EA group, the EA group showed an extension in the total exercise time (P<0.01), the positive expression and mRNA expression levels of α-syn were decreased (P<0.01, P<0.05), while the expression levels of TH, SIRT3, PINK1, Parkin mRNA and SIRT3 protein were increased (P<0.05). CONCLUSIONS: EA at GV16, LR3, and ST36 can exert neuroprotective function and improve the motor ability of PD mice by activating the SIRT3/PINK1/Parkin pathway to enhance the expression of TH and reduce α-syn aggregation in the substantia nigra of PD mice.

Assessment of rTMS treatment effects for methamphetamine use disorder based on EEG microstates.

Microstates have been proposed as topographical maps representing large-scale resting-state networks and have recently been suggested as markers for methamphetamine use disorder (MUD). However, it is unknown whether and how they change after repetitive transcranial magnetic stimulation (rTMS) intervention. This study included a comprehensive subject population to investigate the effect of rTMS on MUD microstates. 34 patients with MUD underwent a 4-week randomized, double-blind rTMS intervention (active=17, sham=17). Two resting-state EEG recordings and VAS evaluations were conducted before and after the intervention period. Additionally, 17 healthy individuals were included as baseline controls. The modified k-means clustering method was used to calculate four microstates (MS-A∼MS-D) of EEG, and the FC network was also analyzed. The differences in microstate indicators between groups and within groups were compared. The durations of MS-A and MS-B microstates in patients with MUD were significantly lower than that in HC but showed significant improvements after rTMS intervention. Changes in microstate indicators were found to be significantly correlated with changes in craving level. Furthermore, selective modulation of the resting-state network by rTMS was observed in the FC network. The findings indicate that changes in microstates in patients with MUD are associated with craving level improvement following rTMS, suggesting they may serve as valuable evaluation markers.

Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome.

Limited treatment options have been shown to alter the natural course of constipation-predominant irritable bowel syndrome (IBS-C). Therefore, safer and more effective approaches are urgently needed. We investigated the effects of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of IBS-C. In the current study, C57BL/6 mice were randomly divided into normal control, IBS-C model control, sham-electrostimulation (sham-ES), taVNS, and drug treatment groups. The effects of taVNS on fecal pellet number, fecal water content, and gastrointestinal transit were evaluated in IBS-C model mice. We assessed the effect of taVNS on visceral hypersensitivity using the colorectal distention test. 16S rRNA sequencing was used to analyze the fecal microbiota of the experimental groups. First, we found that taVNS increased fecal pellet number, fecal water content, and gastrointestinal transit in IBS-C model mice compared with the sham-ES group. Second, taVNS significantly decreased the abdominal withdrawal reflex (AWR) score compared with the sham-ES group, thus relieving visceral hyperalgesia. Third, the gut microbiota outcomes showed that taVNS restored Lactobacillus abundance while increasing Bifidobacterium probiotic abundance at the genus level. Notably, taVNS increased the number of c-kit-positive interstitial cells of Cajal (ICC) in the myenteric plexus region in IBS-C mice compared with the sham-ES group. Therefore, our study indicated that taVNS effectively ameliorated IBS-C in the gut microbiota and ICC.

Effect of electroacupuncture on Nrf2/NLRP3/Caspase-1 pathway mediated-pyroptosis in mice with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å°é¼ Nrf2/NLRP3/Caspase-1通路介导的细胞焦亡的影响.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on nuclear transcription factor E2 related factor 2 (Nrf2)/NOD-like receptor family pyrin domain-containing protein 3 (NLRP3)/cysteine aspartic acid specific protease-1 (Caspase-1) pathway in the substantia nigra (SN) of mice with Parkinson's disease (PD), so as to explore the neuroprotective mechanism of EA. METHODS: Forty C57BL/6 male mice were randomly divided into 4 groups, namely, control, PD model, EA and sham-EA groups, with 10 mice in each group. The PD mouse model was established by gavage of rotenone for 4 weeks. Mice in the EA group were given EA stimulation (1 mA, 2 Hz) at "Fengfu" (GV36), bilateral "Taichong" (LR3) and "Zusanli" (ST36) for 30 min, once daily for 2 consecutive weeks. And mice in the sham-EA group were given acupuncture at the subcutaneous areas of the same acupoints without EA stimulation. The open-field test was used for assessment of mouse behavior. The levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the serum were detected by enzyme-linked immunosorbent assay . The positive expression of tyrosine hydroxylase (TH) in SN was determined by immunohistochemistry. The mRNA expression levels of Nrf2, NLRP3, Caspase-1, gasdermin D(GSDMD), IL-1ß, IL-18 and the protein expression levels of Nrf2, NLRP3, Caspase-1 and GSDMD in the SN were detected by quantitative real-time PCR and Western blot, separately. RESULTS: After modeling, compared with the control group, the behavioral score was increased (P<0.01), the total exercise time, the total distance and the average speed were decreased (P<0.01), and the positive expression of TH and the mRNA and protein expression levels of Nrf2 in the SN were decreased (P<0.01), while the contents of IL-1ß and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD and the mRNA expression levels of IL-1ß and IL-18 in the SN were up-regulated (P<0.01) in the PD model group. Following EA intervention, the behavioral score was decreased(P<0.01), the total exercise time, total distance and average speed were increased (P<0.01), the positive expression of TH and the mRNA and protein expressions of Nrf2 in SN were up-regulated (P<0.01, P<0.05), while the contents of IL-1ß and IL-18 in serum, the mRNA and protein expression levels of NLRP3, Caspase-1 and GSDMD as well as the mRNA expression levels of IL-1ß and IL-18 in the SN were down-regulated (P<0.01, P<0.05) in the EA group relative to the PD model and sham-EA groups. There were no significant differences in the above indicators between the PD model and sham-EA groups. CONCLUSIONS: EA stimulation of GV36, LR3 and ST36 can improve motor deficits, reduce the loss of dopamine neurons in the SN, and inhibit neuroinflammatory responses in mice with PD, which may be related to its effects in regulating the Nrf2/NLRP3/Caspase-1 pathway mediated pyroptosis.

A Novel Demulsifier with Strong Hydrogen Bonding for Effective Breaking of Water-in-Heavy Oil Emulsions.

In the heavy petroleum industry, the development of efficient demulsifiers for the effective breaking of interfacially active asphaltenes (IAA)-stabilized water-in-heavy oil (W/HO) emulsions is a highly attractive but challenging goal. Herein, a novel nitrogen and oxygen containing demulsifier (JXGZ) with strong hydrogen bonding has been successfully synthesized through combining esterification, polymerization and amidation. Bottle tests indicated that JXGZ is effectual in quickly demulsifying the IAA-stabilized W/HO emulsions; complete dehydration (100%) to the emulsions could be achieved in 4 min at 55 °C using 400 ppm of JXGZ. In addition, the effects of demulsifier concentration, temperature and time on the demulsification performance of JXGZ are systematically analyzed. Demulsification mechanisms reveal that the excellent demulsification performance of JXGZ is attributed to the strong hydrogen bonding between JXGZ and water molecules (dual swords synergistic effect under hydrogen bond reconstruction). The interaction of the "dual swords synergistic effect" generated by two types of hydrogen bonds can quickly break the non-covalent interaction force (π-π stacking, Van der Waals force, hydrogen bonds) of IAA at the heavy oil-water interface, quickly promote the aggregation and coalescence of water molecules and finally achieve the demulsification of W/HO emulsions. These findings indicate that the JXGZ demulsifier shows engineering application prospects in the demulsification of heavy oil-water emulsions, and this work provides the key information for developing more efficient chemical demulsifiers suitable for large-scale industrial applications.

Efficient removal of naphthenic acids from real petroleum wastewater by natural pyrite activated persulfate system.

The petroleum wastewater (PWW) contains a diverse range of recalcitrant organic contaminants. Of particular concern is the removal of naphthenic acids (NAs) due to the high toxicity and persistence. Persulfate (PS) based oxidation processes have shown promising in treating refractory wastewater, while the high costs of prepared catalysts limited their widespread implementation. This study aims to develop a cost-effective natural pyrite activated PS system for PWW treatment. The removal of NAs by pyrite/PS system was initially investigated. More than 90% of cyclohexanoic acid (CHA), a model NA, was removed in pyrite/PS system (2.0 g/L pyrite, 4.0 mM PS) at initial pH of 3-11. Scavenging experiments revealed that Fe(II) on pyrite surface was the reactive site for PS activation to generate reactive species, including sulfate radical (SO4·-), Fe(IV) and hydroxyl radical (·OH) for CHA degradation. Reactions of Fe(III) with S helped restore Fe(II) and enhance PS activation, resulting in the sustained catalytic activity of pyrites over five cycles. Cl-, SO42- and NO3- below 10 mM had minimal impact on CHA degradation in pyrite/PS system. However, over 1 mM of HCO3- inhibited 80% of CHA removal due to the buffer effect to maintain the high solution pH. Removing HCO3- from real PWW restored the removal of CHA and of total organic carbon (TOC) to over 90% and 71.3% in pyrite/PS system, respectively. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results indicated that O2‒6 species including NAs were primarily eliminated through mineralization and oxygen addition. Besides, O3-5S, NO3-5S and N3O2‒4 species were the most susceptible to oxidation in PWW, resulting in the increase of the oxidation level (i.e., O/Cwa) from 0.41 to 0.56 after treatment. This study provides valuable insights into the treatment of NAs in real PWW, and potential application of natural minerals in the treatment of industrial wastewater.

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking.

Purpose: Supplemented Erzhi Wan (SEZW) is a Traditional Chinese Medicine commonly used in the treatment of androgenetic alopecia (AGA). This study aims to verify the effectiveness of SEZW for the treatment of AGA in mice and explore the potential molecular mechanisms underlying its function using network pharmacology and molecular docking. Methods: Forty mice were divided into five groups: Control, AGA-model, AGA-Positive, SEZW Low Dose, and SEZW High Dose. Hair regrowth in mice was evaluated by scoring hair on days 0, 14, and 28 post-treatment and weighing mouse hair on day 28 post-treatment. The targets of the active compounds of SEZW were obtained using the Traditional Chinese Medicine Database. AGA-related targets were downloaded from five databases. Then, the overlapping genes were identified. A protein-protein interaction network was constructed using the STRING database. Hub targets were determined through analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Finally, molecular docking of active compounds and hub targets was performed. Results: Hair regrowth in mice in the SEZW treatment groups was significantly enhanced relative to that in the AGA-model mice. A total of 59 potential drug-disease targets were identified. Based on the GO/KEGG analysis results, oxidative stress and gland development were identified as potential mechanisms of action of SEZW in AGA treatment. The PI3K-Akt and AGE-RAGE signaling pathways and seven hub targets were identified as the potential underlying mechanism of SEZW function. Molecular docking results showed that the most active SEZW compounds bind stably to several of the candidate disease targets. Conclusion: SEZW is effective in the treatment of AGA in a mouse model. Combined with network pharmacological analysis, the potential mechanisms, signaling pathways, and hub targets of SEZW in the treatment of AGA were identified, providing new ideas for further studies.

Effects of electroacupuncture on the intestinal thioredoxin interaction protein/Nod-like receptor 3 signaling pathway in mice with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å°é¼ è‚ é“ç¡«æ°§è¿˜è›‹ç™½äº’ä½œè›‹ç™½/NODæ ·å—ä½“3信号通路的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Fengfu" (GV16), "Taichong" (LR3) and "Zusanli" (ST36) on α-synuclein (α-syn), Occludin, Claudin-1, thioredoxin interaction protein (TXNIP) and Nod-like receptor 3 (NLRP3) in Parkinson's disease (PD) mice, so as to investigate the mechanisms of EA on intestinal barrier function and inflammation in PD mice. METHODS: Thirty six C57BL/6 mice were randomly divided into control, model and EA groups, with 12 mice in each group. PD mice model was induced by rotenone intragastric administration for 28 days. Mice in the EA group were treated with EA (2 Hz, 1 mA) at GV16, LR3 and ST36 for 30 min, once a day for 14 days. The behavioral scores were observed. The total distance of autonomic movement was measured by open field test. The expression level of α-syn in substantia nigra and colon tissue was determined by immunohistochemistry. The colonic morphology and goblet cell distribution were observed by Alcian blue staining. The expression levels of Occludin, Claudin-1, TXNIP and NLRP3 mRNA in colon tissue were detected by real-time fluorescence quantitative PCR. RESULTS: Compared with the control group, the behavioral scores of rats were increased (P<0.01)；the total distance of autonomous movement was decreased (P<0.01)；the positive expression level of α-syn in the substantia nigra and colon was increased (P<0.01)；the goblet cells and crypts in colon tissue were reduced, and the muscular layer was thinner；the expression levels of Occludin and Claudin-1 mRNAs in colon tissue were decreased (P<0.01) while TXNIP and NLRP3 mRNAs were increased (P<0.01) in the model group. Compared with the model group, the surface villi of colon tissue was more complete, the goblet cells and crypts were increased, and the muscular layer was thickened；the other indexes were reversed (P<0.01, P<0.05) in the EA group. CONCLUSIONS: EA at GV16, LR3 and ST36 can reduce the abnormal accumulation of α-syn in the substania nigra and colon tissue of PD mice, alleviate the damage of intestinal barrier, regulate TXNIP/NLRP3 signaling pathway, so as to delay the occurrence and development of PD.

Novel Curcumin Analogue L6H4 in Treating Liver Fibrosis and Type 2 Diabetes.

Purpose: The objective of this study was to evaluate the therapeutic efficacy of the curcumin analogue L6H4 in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. Methods: Male Sprague-Dawley rats were fed a high-fat diet to induce insulin resistance, followed by streptozotocin injection to induce diabetes. The rats were then treated with L6H4 for eight weeks. Body weight, metabolic parameters, liver function, and liver histopathology were evaluated. Immunohistochemistry was performed to assess the expression of TGF-ß1, TIMP-2, and MMP-2 in liver tissues. Statistical analysis was conducted using one-way ANOVA and Spearman rank correlation test. Results: L6H4 treatment effectively reversed the weight gain associated with a high-fat diet and improved metabolic parameters in diabetic rats. Liver function markers, such as ALT and AST, were reduced after L6H4 treatment. Histological analysis showed improved liver morphology and reduced fibrosis in L6H4-treated rats. Electron microscopy revealed improved ultrastructural features of hepatocytes. Immunohistochemistry demonstrated downregulation of TGF-ß1 and TIMP-2 expression and restoration of MMP-2 expression in the liver tissue of L6H4-treated rats. Correlation analysis showed a significant positive correlation between TGF-ß1 and TIMP-2 expression. Conclusion: The findings suggest that L6H4 has therapeutic potential in attenuating liver fibrosis and alleviating insulin resistance in streptozotocin-induced diabetic rats. The hepatoprotective effect of L6H4 may be attributed to its anti-inflammatory properties and its ability to target molecules involved in fibrosis. Further research is warranted to explore the potential of L6H4 as a treatment option for nonalcoholic fatty liver disease and type 2 diabetes.

YuPingFengSan ameliorates LPS-induced acute lung injury and gut barrier dysfunction in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Yupingfengsan (YPFS) is a traditional Chinese medicine decoction. YPFS comprises Astragalus mongholicus Bunge (Huangqi), Atractylodes rubra Dekker (Baizhu), and Saposhnikovia divaricata (Turcz.ex Ledeb.) Schischk (Fangfeng). YPFS is commonly used to treat chronic obstructive pulmonary disease, asthma, respiratory infections, and pneumonia, but the mechanism of action remains unclear. AIM OF THE STUDY: Acute lung injury (ALI) and its severe form of acute respiratory distress syndrome (ARDS) cause morbidity and mortality in critical patients. YPFS is a commonly used herbal soup to treat respiratory and immune system diseases. Nevertheless, the effect of YPFS on ALI remains unclear. This study aimed to investigate the effect of YPFS on lipopolysaccharide (LPS)-induced ALI in mice and elucidate its potential molecular mechanisms. MATERIALS AND METHODS: The major components of YPFS were detected by High-performance liquid chromatography (HPLC). C57BL/6J mice were given YPFS for seven days and then treated with LPS. IL-1ß, IL-6, TNF-α, IL-8, iNOS, NLRP3, PPARγ, HO-1, ZO-1, Occludin, Claudin-1, AQP3, AQP4, AQP5, ENaCα, ENaCß, EnaCγ mRNA in lung and ZO-1, Occludin, Claudin-1, AQP3, AQP4, AQP5, ENaCα, ENaCß, and EnaCγ mRNA in colon tissues were measured by Real-Time Quantitative PCR (RT-qPCR). The expressions of TLR4, MyD88, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), ASC, MAPK signaling pathway, Nrf2, and HO-1 in the lung were detected by Western blot. Plasma inflammatory factors Interleukin (IL)-1ß, IL-6, and Tumor Necrosis Factor-α (TNF-α) were determined by Enzyme-linked Immunosorbent Assay (ELISA). Lung tissues were processed for H & E staining, and colon tissues for HE, WGA-FITC, and Alcian Blue staining. RESULTS: The results showed that YPFS administration alleviated lung injury and suppressed the production of inflammatory factors, including IL-1ß, IL-6, and TNF-α. Additionally, YPFS reduced pulmonary edema by promoting the expressions of aquaporin and sodium channel-related genes (AQP3, AQP4, AQP5, ENaCα, ENaCß, and EnaCγ). Further, YPFS intervention exhibited a therapeutic effect on ALI by inhibiting the activation of the NLRP3 inflammasome and MAPK signaling pathways. Finally, YPFS improved gut barrier integrity and suppressed intestinal inflammation in LPS-challenged mice. CONCLUSIONS: YPFS protected mice against LPS-induced ALI by attenuating lung and intestinal tissue damage. This study sheds light on the potential application of YPFS to treat ALI/ARDS.

Molecular and spatial profiling of the paraventricular nucleus of the thalamus.

The paraventricular nucleus of the thalamus (PVT) is known to regulate various cognitive and behavioral processes. However, while functional diversity among PVT circuits has often been linked to cellular differences, the molecular identity and spatial distribution of PVT cell types remain unclear. To address this gap, here we used single nucleus RNA sequencing (snRNA-seq) and identified five molecularly distinct PVT neuronal subtypes in the mouse brain. Additionally, multiplex fluorescent in situ hybridization of top marker genes revealed that PVT subtypes are organized by a combination of previously unidentified molecular gradients. Lastly, comparing our dataset with a recently published single-cell sequencing atlas of the thalamus yielded novel insight into the PVT's connectivity with the cortex, including unexpected innervation of auditory and visual areas. This comparison also revealed that our data contains a largely non-overlapping transcriptomic map of multiple midline thalamic nuclei. Collectively, our findings uncover previously unknown features of the molecular diversity and anatomical organization of the PVT and provide a valuable resource for future investigations.

Effects of mowing on Pb accumulation and transport in Cynodon dactylon (L.) Pers.

Bermudagrass is a perennial herb with the potential to remediate Pb pollution in soils, and it has mechanical resistance to shearing. However, the effects of mowing on Pb absorption and accumulation in bermudagrass are still unclear. In this study, we investigated the effects of different quantities (0, 1, 2, 4 applications) of mowing treatments under 200 mg L-1 Pb application on Pb accumulation and transport in bermudagrass and explored the related mechanisms. Compared to the Pb treatment, all of the mowing treatments greatly decreased root Pb concentration/accumulation, significantly enhanced Pb concentrations/accumulations in stubble stems and stubble leaves, and ultimately promoted Pb enrichment and transport. Of the treatments in this study, two applications of mowing best promoted Pb enrichment, and four applications of mowing best promoted Pb transport efficiency. Furthermore, mowing mediated the microdistribution and physiological patterns of Pb in bermudagrass and affected the Pb transport by changing the subcellar distribution patterns and chemical forms of Pb in various tissues. Additionally, mowing promoted the transport of all mineral elements and showed a synergistic relationship with Pb absorption and transport. The change in mineral element metabolism patterns may be an important reason why mowing promoted Pb accumulation in bermudagrass. Our study provides the first comprehensive evidence regarding mowing facilitating the absorption, accumulation and transport of Pb in bermudagrass. Moderate mowing may be an effective strategy to assist in soil Pb remediation using bermudagrass.

Associations between plant-based diets, plant foods and botanical supplements with gestational diabetes mellitus: a systematic review protocol.

INTRODUCTION: Gestational diabetes mellitus (GDM) is one of the most common health complications during pregnancy. Medical nutrition therapy is the mainstay of treatment for GDM, however, there is no current consensus on optimal dietary approaches to prevent or control hyperglycaemia in pregnancy. The aim of this systematic review is to assess the relationships between plant-based dietary patterns, plant foods and botanical dietary supplements with GDM and maternal glycaemic biomarkers. METHODS AND ANALYSIS: A predefined search strategy was used on 16 June 2021, to search PubMed, Embase and CINAHL Plus with Full Text (EBSCOhost), as well as ClinicalTrials.gov, for studies published as original articles in English. Articles will be included if they are human observational studies or clinical trials and will be excluded if they are review articles or conference abstracts. We will use Cochrane's risk of bias tools for interventions that are parallel arm (Risk of Bias tool for randomised trials version 2 (RoB 2)) and single arm, non-randomised intervention studies (Risk of Bias In Non-randomised Studies-of Interventions (ROBINS-I)). For observational, case-control and cross-sectional studies, we will use the National Heart, Lung and Blood Institute's quality assessment tools. Data will be synthesised in a narrative format describing significant results as well as presenting the results of the quality assessment of studies. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval as primary data will not be collected. The review will be published in a peer-reviewed journal and disseminated electronically and in print. PROSPERO REGISTRATION NUMBER: CRD42022306915.

Allium vegetable intake associated with the risk of incident gastric cancer: a continuous follow-up study of a randomized intervention trial.

BACKGROUND: Allium vegetable components have antibacterial, antioxidative, and immune modulation properties, thus potentially exhibiting antitumor effects. Despite evidence from case-control studies, prospective studies linking allium vegetables with gastric cancer (GC) have been sparse. OBJECTIVE: In a prospective study, we examined whether allium vegetable intake would change the risk of GC occurrence and whether the associations would be modified by vitamin supplementation, garlic supplementation, and Helicobacter pylori (H. pylori) treatment. METHODS: The study was conducted on the basis of the Shandong Intervention Trial, a randomized, placebo-controlled, factorial-designed trial (1995-2003) in a well-recognized high-risk area for GC in China. Participants were continuously followed up to December 2017 for 22.3 y (1995-2017). A total of 3229 subjects were included, with information on the intake of allium vegetables (garlic vegetables and scallions), collected by structured questionnaires in 1994. The associations of total and individual allium vegetable intake with the risk of GC were examined, respectively. RESULTS: During the follow-up, 144 incident cases of GC were identified. Garlic vegetable intake was associated with a decreased risk of incident GC (P-trend = 0.02; OR: 0.83; 95% CI: 0.70, 0.98, per 1 kg/y increment), whereas scallion intake showed no association (P-trend = 0.80). An inverse association of the risk of GC with total allium vegetable and garlic vegetable intake was particularly stronger among those receiving the placebo for vitamin supplementation or garlic supplementation, indicating potential effect modifications by nutritional supplementation on allium vegetable intake and the risk of developing GC. Similar findings were found for analyses of the combined prevalence of dysplasia or GC. CONCLUSIONS: We found a significant reduction in the risk of developing GC with increasing dietary intake of allium vegetables, particularly garlic vegetables. The findings add to the literature on the potential inverse association of garlic vegetable intake with the risk of GC, therefore holding public health implications for dietary recommendations. This trial was registered at clinicaltrials.gov as NCT00339768.

Electron-transfer pathways insights into contaminants oxidized by Cu-OOSO3- intermediate: Effects of oxidation states of Cu and solution pH values.

The copper-peroxy complex (Cu-OOSO3-) metastable intermediate has been confirmed to oxidize contaminants via a single-electron-transfer pathway or an oxygen-atom-transfer pathway. And the effects of Cu oxidation states and reaction pH conditions on the intermediate properties have not been explored in depth. Here, copper oxide (CuOx) catalysts with different Cu oxidation states were synthesized by a simple precipitation method by controlling the reaction temperature from 0 to 45 °C. CuOx displayed a strong catalytic dependence on the Cu oxidation state, and CuOx-30 with Cu average valence on the catalyst surface of 1.61 was more reactive for catalytic degradation of bisphenol A with peroxymonosulfate (PMS). Notably, CuOx-30, with the best electron-accepting ability, was easier to bonding with PMS to form the Cu-OOSO3- reactive complex, and the generated intermediate exhibited the strongest capacity to obtain electrons from contaminants. Moreover, the electron-transfer pathways were closely related to the average valence of Cu, and the contribution of the oxygen-atom-transfer pathway changed volcanic with increasing Cu valence. Meanwhile, the reaction predominantly involved the oxygen-atom-transfer pathway under acidic conditions (pH=3), while the contribution of the single-electron-transfer pathway raised with increasing pH values. Hence, this work was devoted to providing new insights into the CuOx-inducing PMS activation and vital supplementary to the properties of the Cu-OOSO3- intermediate.

Ligusticum chuanxiong promotes the angiogenesis of preovulatory follicles (F1-F3) in late-phase laying hens.

Ligusticum chuanxiong (CX) is a traditional Chinese medicine that is widely planted throughout the world. CX is one of the most important and commonly used drugs to enhance blood circulation. The preovulatory follicles in laying hens have a large number of blood arteries and meridians that feed the follicles' growth and maturation with nutrients, hormones, and cytokines. With the extension of laying time, preovulatory follicles angiogenesis decreased gradually. In this study, we studied the mechanism of CX on preovulatory follicles angiogenesis in late-phase laying hens. The results show that CX extract can increase the angiogenesis of preovulatory follicles (F1-F3) of late-phase laying hens. CX extract can promote vascular endothelial growth factor receptor 2 (VEGFR2) phosphorylation in preovulatory follicles theca layers, promote the proliferation, invasion and migration through PI3K/AKT and RAS/ERK signaling pathways in primary follicle microvascular endothelial-like cells (FMECs). In addition, CX extract can up-regulate the expression of hypoxia inducible factor α (HIF1α) in granulosa cells (GCs) and granulosa layers through PI3K/AKT and RAS/ERK signaling pathways, thereby promoting the secretion of vascular endothelial growth factor A (VEGFA). In conclusion, the current study confirmed the promoting effect of CX extract on the preovulatory follicles angiogenesis, which sets the stage for the design of functional animal feed for late-phase laying hens.

Precisely designed Fex (x = 1-2) cluster nanocatalysts for effective nanocatalytic tumor therapy.

Atomically dispersed metal clusters are considered as promising nanocatalysts due to their excellent physicochemical properties. Here, we report a novel strategy for precisely designing Fex (x = 1-2) cluster nanocatalysts (Fe1-N-C and Fe2-N-C) with dual catalytic activity, which can catalyze H2O2 into reactive oxygen species (ROS) and oxidize glutathione (GSH) into glutathione disulfide simultaneously. The adsorption energies of Fe-N sites in Fe2-N-C for GSH and H2O2 intermediates were well controlled due to the orbital modulation of adjacent Fe sites, contributing to the higher dual catalytic activity compared to Fe1-N-C. Additionally, tamoxifen (TAM) was loaded into Fe2-N-C (Fe2@TDF NEs) to down-regulate the intracellular pH for higher Fenton-like catalytic efficiency and ROS production. The generated ROS could induce apoptosis and lipid peroxidation, triggering ferroptosis. Meanwhile, upregulation of ROS and lipid peroxidation, along with GSH depletion and GPX4 downregulation could promote the apoptosis and ferroptosis of tumor cells. In addition, the lactic acid accumulation effect of TAM and the high photothermal conversion ability of Fe2@TDF NEs could further enhance the catalytic activity to achieve synergistic antitumor effects. As a result, this work highlights the critical role of adjacent metal sites at the atomic-level and provides a rational guidance for the design and application of nanocatalytic antitumor systems.