New depside and rosmarinic acid derivatives from Perilla frutescens and their anti-inflammatory activity.

Two new depside derivatives 1 and 2 as well as a new pair of rosmarinic acid enantiomers 3a/b were isolated from the leaves of Perilla frutescens (L.) britt. The chemical structures of these compounds were identified based on detailed spectroscopic and physicochemical analyses (HR-ESI-MS, NMR) and comparison of literature data. Compounds 3a/b were obtained by chiral separation, and their absolute configurations were determined by comparison of experimental and calculated ECD spectra. Compounds 3a/b exhibited potential inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC50 values of 15.92 ± 3.32 µM and 48.72 ± 4.12 µM.

[Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis].

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1ß(IL-1ß) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1ß showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

Coupled Processes Involving Organic Matter and Fe Oxyhydroxides Control Geogenic Phosphorus Enrichment in Groundwater Systems: New Evidence from FT-ICR-MS and XANES.

The enrichment of geogenic phosphorus (P) in groundwater systems threatens environmental and public health worldwide. Two significant factors affecting geogenic P enrichment include organic matter (OM) and Fe (oxyhydr)oxide (FeOOH). However, due to variable reactivities of OM and FeOOH, variable strategies of their coupled influence controlling P enrichment in groundwater systems remain elusive. This research reveals that when the depositional environment is enriched in more labile aliphatic OM, its fermentation is coupled with the reductive dissolution of both amorphous and crystalline FeOOHs. When the depositional environment is enriched in more recalcitrant aromatic OM, it largely relies on crystalline FeOOH acting concurrently as electron acceptors while serving as "conduits" to help itself stimulate degradation and methanogenesis. The main source of geogenic P enriched by these two different coupled processes is different: the former is P-containing OM, which mainly contained unsaturated aliphatic compounds and highly unsaturated-low O compounds, and the latter is P associated with crystalline FeOOH. In addition, geological setting affects the deposition rate of sediments, which can alter OM degradation/preservation, and subsequently affects geochemical conditions of geogenic P occurrence. These findings provide new evidence and perspectives for understanding the hydro(bio)geochemical processes controlling geogenic P enrichment in alluvial-lacustrine aquifer systems.

Probiotics alleviate constipation and inflammation in late gestating and lactating sows.

Constipation and systemic inflammation are common in late pregnant and lactating sows, which cause health problems like uteritis, mastitis, dystocia, or even stillbirth, further influencing piglets' survival and growth. Probiotic supplementation can improve such issues, but the beneficial mechanism of relieving constipation and enhancing gut motility remains underexplored. This study aimed to investigate the effects and mechanism of probiotic supplementation in drinking water to late pregnant sows on constipation, inflammation, and piglets' growth performance. Seventy-four sows were randomly allocated to probiotic (n = 36) and control (n = 38) groups. Probiotic treatment significantly relieved sow constipation, enhanced serum IL-4 and IL-10 levels while reducing serum IL-1ß, IL-12p40, and TNF-α levels, and increased piglet daily gain and weaning weight. Furthermore, probiotic administration reshaped the sow gut bacteriome and phageome structure/diversity, accompanied by increases in some potentially beneficial bacteria. At 113 days of gestation, the probiotic group was enriched in several gut microbial bioactive metabolites, multiple carbohydrate-active enzymes that degrade pectin and starch, fecal butyrate and acetate, and some serum metabolites involved in vitamin and amino acid metabolism. Our integrated correlation network analysis revealed that the alleviation of constipation and inflammation was associated with changes in the sow gut bacteriome, phageome, bioactive metabolic potential, and metabolism.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

Probiotic Supplement for the Prevention of Gestational Diabetes: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Probiotic supplements may have some potential in preventing gestational diabetes, and this meta-analysis aims to explore the efficacy of probiotic supplements to prevent gestational diabetes. METHODS: PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of probiotic supplements on the incidence of gestational diabetes mellitus. Meta-analysis was performed using the fixed-effect or random-effect model as appropriate. RESULTS: Six RCTs were finally included in the meta-analysis. Overall, compared with control intervention in pregnant women, probiotic supplementation intervention showed no obvious impact on the incidence of gestational diabetes (OR=0.68; 95% CI=0.39 to 1.20; P=0.18), fasting plasma glucose (SMD=-0.05; 95% CI=-0.29 to 0.19; P=0.69), 2 h-OGTT (SMD=-0.07; 95% CI=-0.27 to 0.13; P=0.47), gestational age (SMD=0.04; 95% CI=-0.14 to 0.21; P=0.69) or preeclampsia (OR=1.22; 95% CI=0.83 to 1.78; P=0.31). CONCLUSIONS: Probiotic supplementation was confirmed to have no benefits for the prevention of gestational diabetes.

Treatment of tibial large bone defects: A comparative study of bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate versus bone transport alone with antibiotic-impregnated calcium sulphate.

PURPOSE: To compare the bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate versus bone transport alone with antibiotic-impregnated calcium sulphate for the treatment of tibial large bone defects. METHODS: A retrospective analysis was conducted by enroling 33 surgically treated patients with tibial large bone defects after the debridement for tibial infection or osteomyelitis who were admitted in Lower Limb Surgery Ward of Traumatic orthopaedic Department, Xi'an Honghui Hospital from January 2018 to January 2021. All the patients were categorized in Group A (transport over intramedullary nail, 12 cases) and Group B (transport alone, 21 cases) based on the surgery strategy. The collected clinical materials and data included gender, age, injury mechanism, smoking habits, comorbidity diseases, initial fracture type (open or close), bone defect size, surgical duration, intraoperative bleeding loss, resorption time of calcium sulphate, bone transport time, external fixation time, external fixation index, weight bearing time, complications and Paley bone and functional criteria. RESULTS: Thirty-three patients were enroled and successfully followed up with an average time of 15.25±4.31 months ranged from 8 to 21 months in Group A and an average time of 17.09±5.64 months ranged from 9 to 31 months in Group B. No significantly statistical differences of the demographic data were discovered between the two groups. There were no significantly statistical differences of the average bone defect size, intraoperative bleeding loss, resorption time of calcium sulphate and bone transport time between the two groups. However, the average surgical duration (P = 0.002) was significantly longer in Group A than Group B and the average external fixation time (P<0.001), external fixation index(P = 0.002) and weight bearing time (P = 0.030) were significantly shorter in Group A than Group B. No significantly statistical difference of excellent and good rate of bone outcomes and complication rate was observed, however, the excellent and good rate of functional outcomes (P = 0.041) was significantly higher in Group A than Group B. CONCLUSION: Compared with the conventional Ilizarov technique combining with antibiotic-impregnated calcium sulphate for large tibial bone defects, bone transport over an intramedullary nail in combination with antibiotic-impregnated calcium sulphate had favourable external fixation time, external fixation index, weight bearing time and clinical functional outcomes which effectively suppressed the infection and allowed patients earlier removal of the external fixator and weight bearing for rehabilitation.

Osthole Suppresses Knee Osteoarthritis Development by Enhancing Autophagy Activated via the AMPK/ULK1 Pathway.

Knee osteoarthritis (KOA) is an increasingly prevalent heterogeneous disease characterized by cartilage erosion and inflammation. As the main chemical constituent of Angelicae Pubescentis Radix (APR), an anti-inflammatory herbal medicine, the potential biological effects and underlying mechanism of osthole on chondrocytes and KOA progression remain elusive. In this study, the potential effect and mechanism of osthole on KOA were investigated in vitro and in vivo. We found that osthole inhibited IL-1ß-induced apoptosis and cartilage matrix degeneration by activating autophagy in rat chondrocytes. In addition, osthole could activate autophagy through phosphorylation of AMPK/ULK1, and AMPK serves as a positive upstream regulator of ULK1. Furthermore, KOA rats treated with osthole showed phosphorylation of the AMPK/ULK1 pathway and autophagy activation, as well as cartilage protection. Collectively, the AMPK/ULK1 signaling pathway can be activated by osthole to enhance autophagy, thereby suppressing KOA development. Osthole may be a novel and effective therapeutic agent for the clinical treatment of KOA.

Clinical Application Effects of Different Preoperative Blood Management Schemes in Older Patients with Delayed Intertrochanteric Fracture Surgery.

Introduction: Research on preoperative blood management in older patients with delayed surgery for intertrochanteric fracture is scarce, especially regarding hematopoiesis and hemostasis. We assessed the effectiveness of optimized blood management programs in older patients undergoing delayed surgery for intertrochanteric fractures. Methods: This retrospective study included 456 patients who underwent delayed surgery for intertrochanteric fractures. According to the optimized blood management plan, the patients were divided into four groups: group A was the control group; group B received 1 g of tranexamic acid (TXA) intravenously at admission; group C underwent sequential TXA treatment after admission until 1 day before surgery (1 g/day); and group D received iron supplements (200 mg/day) in addition to the treatment administered to group C, with or without recombinant human erythropoietin (rHuEPO; 40,000 IU). The primary outcomes were preoperative hidden blood loss (HBL), preoperative allogeneic blood transfusion (ABT) rate, hemoglobin (Hb) change, and actual Hb drop. Results: The Hb reduction, calculated HBL, and hospitalization duration in groups C and D were significantly lower than those in groups A and B. The preoperative ABT rates in groups C and D were significantly lower than those in groups A and B, with no significant difference between groups C and D. Discussion: The results of this study suggested that iron supplementation (with or without rHuEPO) combined with the sequential IV TXA scheme did not show a better clinical effect than the sequential IV TXA scheme in the management of patients undergoing delayed surgery for intertrochanteric fractures. Therefore, further evaluation is needed before recommending iron supplements and rHuEPO in older patients.

Anionic Cyanine J-Type Aggregate Nanoparticles with Enhanced Photosensitization for Mitochondria-Targeting Tumor Phototherapy.

Cyanines have been widely used as the photosensitizers (PSs) in the biomedical field, but controlling their molecular aggregates in nanoparticles (NPs) remains a major challenge. Moreover, the impact of aggregate behaviors of cyanines on the photosensitization is still unclear. Herein, the first anionic cyanine PSs based on a tricyanofuran end group have been designed by achieving supramolecular J-type aggregates in NPs via counterion engineering. Our results indicate that J-type aggregates in NPs can not only bring significantly red-shifted emission, negatively charged surface, and high photostability, but also enable a significant 5-fold increase in singlet oxygen generation efficiency compared to that in the nonaggregate state, providing strong experimental evidence for the superiority of J-aggregates in enhancing photosensitization. Thus, combined with the mitochondria-targeting ability, the J-type aggregate NPs show remarkable in vivo antitumor phototheranostic efficacy, making them have a potential for clinical use.

Bifidobacterium lactis Probio-M8 Adjuvant Treatment Confers Added Benefits to Patients with Coronary Artery Disease via Target Modulation of the Gut-Heart/-Brain Axes.

Accumulating evidence suggests that gut dysbiosis may play a role in cardiovascular problems like coronary artery disease (CAD). Thus, target steering the gut microbiota/metabolome via probiotic administration could be a promising way to protect against CAD. A 6-month randomized, double-blind, placebo-controlled clinical trial was conducted to investigate the added benefits and mechanism of the probiotic strain, Bifidobacterium lactis Probio-M8, in alleviating CAD when given together with a conventional regimen. Sixty patients with CAD were randomly divided into a probiotic group (n = 36; received Probio-M8, atorvastatin, and metoprolol) and placebo group (n = 24; placebo, atorvastatin, and metoprolol). Conventional treatment significantly improved the Seattle Angina Questionnaire (SAQ) scores of the placebo group after the intervention. However, the probiotic group achieved even better SAQ scores at day 180 compared with the placebo group (P < 0.0001). Moreover, Probio-M8 treatment was more conducive to alleviating depression and anxiety in patients (P < 0.0001 versus the placebo group, day 180), with significantly lower serum levels of interleukin-6 and low-density lipoprotein cholesterol (P < 0.005 and P < 0.001, respectively). In-depth metagenomic analysis showed that, at day 180, significantly more species-level genome bins (SGBs) of Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, and Butyricicoccus porcorum were detected in the probiotic group compared with the placebo group, while the abundances of SGBs representing Flavonifractor plautii and Parabacteroides johnsonii decreased significantly among the Probio-M8 receivers (P < 0.05). Furthermore, significantly more microbial bioactive metabolites (e.g., methylxanthine and malonate) but less trimethylamine-N-oxide and proatherogenic amino acids were detected in the probiotic group than placebo group during/after intervention (P < 0.05). Collectively, we showed that coadministering Probio-M8 synergized with a conventional regimen to improve the clinical efficacy in CAD management. The mechanism of the added benefits was likely achieved via probiotic-driven modulation of the host's gut microbiota and metabolome, consequently improving the microbial metabolic potential and serum metabolite profile. This study highlighted the significance of regulating the gut-heart/-brain axes in CAD treatment. IMPORTANCE Despite recent advances in therapeutic strategies and drug treatments (e.g., statins) for coronary artery disease (CAD), CAD-related mortality and morbidity remain high. Active bidirectional interactions between the gut microbiota and the heart implicate that probiotic application could be a novel therapeutic strategy for CAD. This study hypothesized that coadministration of atorvastatin and probiotics could synergistically protect against CAD. Our results demonstrated that coadministering Probio-M8 with a conventional regimen offered added benefits to patients with CAD compared with conventional treatment alone. Our findings have provided a wide and integrative view of the pathogenesis and novel management options for CAD and CAD-related diseases.

Size-Transformable Bicomponent Peptide Nanoparticles for Deep Tumor Penetration and Photo-Chemo Combined Antitumor Therapy.

The suitable size of multifunctional nanomedicines strongly influences their physicochemical properties and actions in biological systems, for example, prolonged blood circulation time, efficient tumor accumulation, and deep tumor penetration. However, it is still a great challenge to construct size-transformable nanoparticles (NPs) for both efficient accumulation and penetration throughout tumor tissue. Herein, a size-transformed multifunctional NP is developed through a simple bicomponent assembling strategy for enhanced tumor penetration and efficient photo-chemo combined antitumor therapy, due to the acidic tumor microenvironment and near infrared-laser irradiation induced size-shrink. This multifunctional bicomponent NP (PP NP) driven by electrostatic interaction is composed of negatively charged peptide amphiphile (PA1) and positively charged peptide prodrug (PA2). PP NPs (≈170 nm) have been proven to improve blood circulation time and stability in biological environments. Interestingly, PP NPs can reassemble small NPs (<30 nm) by responding to acidic tumor microenvironment and near-infrared laser irradiation, which facilitates deep tumor penetration and improves cellular internalization. By integrating fluorescence imaging, tumor targeting, deep tumor penetration, and combined photo-chemotherapy, PP NPs exhibit excellent in vivo antitumor efficacy. This study might provide an insight for developing a bicomponent assembling system with efficient tumor penetration and multimode for antitumor therapy.

[Systematic review and sequential analysis of Tanshinone â ¡_A Sodium Sulfonate Injection combined with enalapril in treatment of acute exacerbation of pulmonary heart disease].

To systematically evaluate the clinical efficacy and safety of Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril in the treatment of patients with acute exacerbation of pulmonary heart disease. The randomized controlled trial(RCT) on Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril for acute exacerbation of pulmonary heart disease was screened from EMbase, PubMed, Web of Science, Cochrane Library, VIP, CNKI, and Wanfang from inception to March 20, 2022. Meta-analysis of each index was performed in RevMan 5.3 and TSA 0.9. Finally, 41 RCTs involving 3 865 patients were included. Meta-analysis showed that the observation group had higher total response rate(RR=1.21, 95%CI[1.18, 1.24], P<0.000 01), lower plasma viscosity(MD=-0.25, 95%CI[-0.34,-0.16], P<0.000 01), lower whole blood viscosity(MD=-0.99, 95%CI[-1.14,-0.85], P<0.000 01), and lower hematokrit(MD=-9.03, 95%CI[-10.57,-7.50], P<0.000 01) than the control group. The incidence of adverse effects showed no significant difference between groups(RR=1.42, 95%CI[0.82, 2.45], P=0.21). Sequential analysis showed that Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril exerted definite efficacy in the treatment of acute exacerbation of pulmonary heart disease, and the possibility of false positives was excluded. Based on the existing evidence, Tanshinone Ⅱ_A Sodium Sulfonate Injection combined with enalapril can improve the total response rate and reduce plasma viscosity, whole blood viscosity, and hematocrit, demonstrating good safety in patients with acute exacerbation of pulmonary heart disease. In the future, more RCT with large sample size, rigorous design, and in accordance with international norms are needed to further validate the results.

Antibiotic calcium sulfate-loaded hybrid transport versus traditional Ilizarov bone transport in the treatment of large tibial defects after trauma.

BACKGROUND: The purpose of this study was to compare the clinical effects of antibiotic calcium sulfate-loaded hybrid transport (ACSLHT) and traditional Ilizarov bone transport (TIBT) in the treatment of large tibial defects after trauma. METHODS: Eighty-five patients with large tibial defects after trauma were selected for retrospective study. The range of tibial defects was 6-22 cm. After thorough debridement and infection controlled, bone transport technique was used to reconstruct tibial defects. Forty-four patients were treated with ACSLHT technique (the ACSLHT group), while the other 41 were treated with TIBT technique (the TIBT group). Time in external fixator was evaluated by EFI score. Enneking score was used to evaluate limb functions. SAS score was used to evaluate postoperative anxiety status. In addition, complication incidence was compared, including axis deviation, docking site nonunion, infection recurrence and so on. RESULTS: There was no significant difference in preoperative general data between ACSLHT and TIBT group. EFI score in ACSLHT and TIBT group was 0.6 ± 0.1 cm/month and 1.7 ± 0.3 cm/month, respectively (P < 0.05). Enneking score of ACSLHT and TIBT group was 86.5% and 75.1% (P < 0.05). SAS score of ACSLHT group was significantly lower than that of TIBT group (P < 0.05). Complication incidence in ACSLHT group was significantly lower than that in TIBT group (P < 0.05). CONCLUSIONS: Compared with TIBT group, ACSLHT group had shorter time in external fixator, better limb functions, lower postoperative anxiety score and lower complication incidence which is worth of clinical promotion.

Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes.

BACKGROUND: A crosstalk exists between diabetes and Alzheimer's disease (AD), and diabetic encephalopathy displays AD-like disorders. Sarsasapogenin (Sar) has strong anti-inflammatory efficacy, showing neuroprotection and memory-enhancement effects. PURPOSE: This study aims to verify the ameliorative effects of Sar on diabetic encephalopathy in vivo and in vitro, and to clarify the mechanisms from attenuation of AD-like pathology. METHODS: Streptozotocin-induced type 1 diabetic rats and high glucose-cultured SH-SY5Y cells were used in this study. After Sar treatment (20 and 60 mg/kg) for consecutive 9 weeks, Morris water maze and novel object recognition tasks were performed. Hematoxylin-eosin staining was used for examining loss of neurons in CA1 area and ki67 expression for reflecting neurogenesis in DG area of hippocampus. Aß production pathway and tau phosphorylation kinase cascade were examined in these two models. RESULTS: Sar improved learning and memory ability, loss of neurons and reduction of neurogenesis in the hippocampus of diabetic rats. Moreover, Sar suppressed Aß overproduction due to up-regulation of BACE1 in protein and mRNA and tau hyperphosphorylation from inactivation of AKT/GSK-3ß cascade in the hippocampus and cerebral cortex of diabetic rats and high glucose-cultured SH-SY5Y cells, and PPARγ antagonism abolished the effects of Sar on key molecules in the two pathways. Additionally, it was found that high glucose-stimulated Aß overproduction was prior to tau hyperphosphorylation in neurons. CONCLUSION: Sar alleviated diabetic encephalopathy, which was obtained through inhibitions of Aß overproduction and tau hyperphosphorylation mediated by the activation of PPARγ signaling. Hence, Sar is a good candidate compound for AD-like disorders.

Phosphorus cycling in freshwater lake sediments: Influence of seasonal water level fluctuations.

Freshwater lakes experience drastic water level fluctuations because of climate change and human activities. However, the influence of such fluctuations on phosphorus cycling in sediments has rarely been investigated. We conducted a geochemical investigation on the phosphorus cycle in a shallow freshwater lake, Dongting Lake; under the influence of human activities and climate change, its water regime undergoes drastic changes. Irrespective of the permanent inundation zone (PIZ) or seasonal inundation zone (SIZ), the phosphorus cycle in sediments was found to be dominated by the reductive dissolution of iron (Fe) (oxyhydr)oxides, degradation of organic matters, and conversion between authigenic phosphorus (Ca-P) and detrital phosphorus in individual seasons. From winter to summer, with increasing water level, the content of Fe-bound phosphorus and organic phosphorus increase due to the deposition of suspended matter, thus increasing total phosphorus in PIZ. Moreover, the rising water level also reduces the dissolved oxygen content and promotes the reductive dissolution of Fe (oxyhydr)oxides. The mineralization of increased organic matter can release CO2 and reduce pH in the vicinity, which can further result in the acidic dissolution of detrital apatite. In turn, most of the released phosphorus can be adsorbed or co-precipitated with calcium minerals, resulting in the significant increase of Ca-P. The mechanisms of phosphorus transformation in SIZ are similar to those in PIZ, but most of the increased organic matter and total P in a core from SIZ are attributable to the decomposition of plant matter. Therefore, the water level rise not only changes the conservative speciation of phosphorus in sediments to active speciation, but also triggers the release of phosphorus adsorbed to oxides and further increases the risk of phosphorus release from sediments to overlying water. Thus, our findings have major implications for freshwater shallow lakes and their P-driven productivity.

Sarsasapogenin ameliorates diabetes-associated memory impairment and neuroinflammation through down-regulation of PAR-1 receptor.

Sarsasapogenin (Sar), a natural steroidal compound, shows neuroprotection, cognition-enhancement, antiinflammation, antithrombosis effects, and so on. However, whether Sar has ameliorative effects on diabetes-associated cognitive impairment remains unknown. In this study, we found that Sar ameliorated diabetes-associated memory impairment in streptozotocin-induced diabetic rats, evidenced by increased numbers of crossing platform and percentage of time spent in the target quadrant in Morris water maze tests, and suppressed the nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) inflammasome in hippocampus and cerebral cortex. Furthermore, Sar inhibited advanced glycation end-products and its receptor (AGEs/RAGE) axis and suppressed up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) in cerebral cortex. On the other hand, Sar mitigated high glucose-induced neuronal damages, NLRP1 inflammasome activation, and PAR-1 up-regulation in high glucose-cultured SH-SY5Y cells, but did not affect thrombin activity. Moreover, the effects of Sar were similar to those of a selective PAR-1 antagonist vorapaxar. Further studies indicated that activation of the NLRP1 inflammasome and NF-κB mediated the effect of PAR-1 up-regulation in high glucose condition by using PAR-1 knockdown assay. In summary, this study demonstrated that Sar prevented memory impairment caused by diabetes, which was achieved through suppressing neuroinflammation from activated NLRP1 inflammasome and NF-κB regulated by cerebral PAR-1. HIGHLIGHTS: Sarsasapogenin ameliorated memory impairment caused by diabetes in rats. Sarsasapogenin mitigated neuronal damages and neuroinflammation by down-regulating cerebral PAR-1. The NLRP1 inflammasome and NF-κB signaling mediated the pro-inflammatory effects of PAR-1. Sarsasapogenin was a pleiotropic neuroprotective agent and memory enhancer in diabetic rodents.

Probiotic consumption relieved human stress and anxiety symptoms possibly via modulating the neuroactive potential of the gut microbiota.

Stress has been shown to disturb the balance of human intestinal microbiota and subsequently causes mental health problems like anxiety and depression. Our previous study showed that ingesting the probiotic strain, Lactobacillus (L.) plantarum P-8, for 12 weeks could alleviate stress and anxiety of stressed adults. The current study was a follow-up work aiming to investigate the functional role of the gut metagenomes in the observed beneficial effects. The fecal metagenomes of the probiotic (n = 43) and placebo (n = 36) receivers were analyzed in depth. The gut microbiomes of the placebo group at weeks 0 and 12 showed a significantly greater Aitchison distance (P < 0.001) compared with the probiotic group. Meanwhile, the Shannon diversity index of the placebo group (P < 0.05) but not the probiotic group decreased significantly at week 12. Additionally, significantly more species-level genome bins (SGBs) of Bifidobacterium adolescentis, Bifidobacterium longum, and Fecalibacterium prausnitzii (P < 0.01) were identified in the fecal metagenomes of the probiotic group, while the abundances of SGBs representing the species Roseburia faecis and Fusicatenibacter saccharivorans decreased significantly (P < 0.05). Furthermore, the 12-week probiotic supplementation enhanced the diversity of neurotransmitter-synthesizing/consuming SGBs and the levels of some predicted microbial neuroactive metabolites (e.g., short-chain fatty acids, gamma-aminobutyric acid, arachidonic acid, and sphingomyelin). Our results showed a potential link between probiotic-induced gut microbiota modulation and stress/anxiety alleviation in stressed adults, supporting that the gut-brain axis was involved in relieving stress-related symptoms. The beneficial effect relied not only on microbial diversity changes but more importantly gut metagenome modulations at the SGB and functional gene levels.

Efficacy and safety of retention enema with traditional Chinese medicine for ulcerative colitis: A meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy and safety of retention enema with traditional Chinese medicine (TCM) for ulcerative colitis (UC) through a meta-analysis of published studies. METHODS: Literatures were retrieved from five electronic databases. Quality evaluation and meta-analysis were respectively conducted using the Cochrane collaboration and RevMan5.3. Overall quality of evidence was evaluated using GRADE system. Effect sizes were pooled using random effect models. RESULTS: Seventeen RCTs were included. Compared with routine pharmacotherapies (RPs), TCM enema exhibited a statistically significant difference in clinical efficacy and reduction of the recurrence rate. The results of qualitative description for other endpoints, such as improvements in anabrosis, ulcer, diarrhea, and hematochezia, suggested that TCM enema had better efficacy than RPs. Furthermore, the incidence of side effects in TCM was lower than that in RPs. CONCLUSION: This meta-analysis confirmed the efficacy and safety of TCM enema for improving UC symptoms. However, further well-designed researches are needed.

Tumor targeted combination therapy mediated by functional macrophages under fluorescence imaging guidance.

Imaging-guiding and targeted drug delivery to tumors are essential for precision cancer therapy, which is a challenging goal to achieve extraordinary therapeutic efficacy. Functional live cells-based delivery systems are expected to play an important role in imaging-guiding and targeted drug delivery. Herein, we fabricated a delivery system mediated by IR-820 conjugated macrophages for tumor targeted combination therapy under fluorescence imaging guidance. The functional macrophages by nature could cross the barriers and recruit into tumors, and serve as host cells to targeted deliver drugs to tumors. The pH-sensitive doxorubicin nanoparticles were engulfed by the macrophages to enhance the drug loading and decrease the damage on host cells. IR-820 was anchored into macrophages cytoplasm to achieve the dual function of photothermal therapy and fluorescence imaging guidance. With Balb/C mice bearing murine breast tumor (4 T1) as models, the functional macrophages for their innate tumor tropism could targeted transport these therapeutic drugs into tumor site to exert efficient chemo-photothermal combination therapy. Moreover, fluorescence imaging-guided drug delivery was employed as the visible strategy to provide the optimized therapeutic window based on the fluorescence of IR-820. The multi-functional macrophages-mediated delivery system would provide a potential for precise and targeted delivery of combination therapy.