Sishen Pill and its active phytochemicals in treating inflammatory bowel disease and colon cancer: an overview.

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

Predictive models for perceived convenience of accessing outdoor activities among elderly with physical disabilities in rural China.

BACKGROUND: The elderly, especially those with physical disabilities, often encounter barriers that prevent them from accessing outdoor activities. Their perceptions of the convenience of accessing outdoor activities may be influenced by various factors including their health, the social context, and/or planned behavior. This study aimed to develop predictive models that identify the principal determinants of perceived convenience among this demographic, and it also examined the disparities observed between genders. METHODS: This was a cross-sectional survey of 1216 community-dwelling older people with physical disabilities in rural China. Grounded on the rehabilitation concepts and the theory of planned behavior, structural equation models integrated health and social behavior factors were constructed to predict perceived convenience of accessing outdoor activities. The standardized coefficients explained the contributions of various factors to the variance. RESULTS: The final structural models demonstrated good fit for both female and male participants. Perceptions of the convenience of accessing outdoor activities among both women and men were directly impacted by their physical functioning and their intention to participate, and indirectly by medical expenditure, subjective norms, pain, and role limitation in emotional interactions. Positive mental health was more influential for women, while men were more influenced by subjective norms. CONCLUSIONS: Structural equation models have effectively predicted the self-reported convenience of accessing outdoor activities, underscoring the importance of functional and behavioral rehabilitation. Furthermore, gender-sensitive rehabilitation programs are advised to promote engagement in outdoor activities among elderly individuals with physical disabilities.

Pharmacodynamic components and mechanisms of ginger (Zingiber officinale) in the prevention and treatment of colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginger is a "medicine-food homology" natural herb and has a longstanding medicinal background in treating intestinal diseases. Its remarkable bioactivities, including anti-inflammatory, antioxidant, immunoregulatory, flora regulatory, intestinal protective, and anticancer properties, make it a promising natural medicine for colorectal cancer (CRC) prevention and treatment. AIM OF THE REVIEW: The purpose is to review the relevant literature on ginger and pharmacodynamic components for CRC prevention and treatment, summarize the possible mechanisms of ginger from clinical studies and animal and in vitro experiments, to provide theoretical support for the use of ginger preparations in the daily prevention and clinical treatment of CRC. MATERIALS AND METHODS: Literatures about ginger and CRC were searched from electronic databases, such as PubMed, Web of Science, ScienceDirect, Google Scholar and China National Knowledge Infrastructure (CNKI). RESULTS: This article summarizes the molecular mechanisms of ginger and its pharmacodynamic components in the prevention and treatment of CRC, including anti-inflammatory, antioxidant, immunoregulatory, flora regulatory, intestinal protective, inhibit CRC cell proliferation, induce CRC cell cycle blockage, promote CRC cell apoptosis, suppress CRC cell invasion and migration, enhance the anticancer effect of chemotherapeutic drugs. CONCLUSIONS: Ginger has potential for daily prevention and clinical treatment of CRC.

Molecular mechanisms of Chengshi Beixie Fenqing Decoction based on network pharmacology: pivotal roles of relaxin signaling pathway and its associated target proteins against Benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common disease that affects the quality of life of middle-aged and older men. We investigated the therapeutical effects of Chengshi Beixie Fenqing Decoction (CBFD), a classic traditional Chinese medicine prescription, on BPH through in vivo model and network pharmacology. Bioactives in CBFD were detected through UPLC-Q-Tof-MS/MS and GC-MS, and filtered by the modified Lipinski's rule. Target proteins associated with the filtered compounds and BPH are selected from public databases. Venn diagram identified the overlapping target proteins between the bioactives-interacted target proteins and the BPH-targeted proteins. The bioactive-protein interactive networking of BPH was analyzed through the KEGG pathway on STRING to identify potential ligand-target and visualized the rich factors on the R packet. After that, the molecular docking test (MDT) was performed between bioactives and target proteins. It showed that the mechanism of CBFD against BPH was related to 104 signaling pathways of 42 compounds. AKT1, 6-demethyl-4'-methyl-N-methylcoclaurine and relaxin signaling pathways were selected as a hub target, key bioactivitie and hub signaling pathway, respectively. In addition, three major compounds, 6-demethyl-4'-methyl-N-methylcoclaurine, isoliensinine and liensinine, had the highest affinity on MDT for the three crucial target proteins, AKT1, JUN and MAPK1. These proteins were associated with the relaxin signaling pathway, which regulated the level of nitric oxide and is implicated in both BPH development and CBFD. We concluded that the three key bioactivities found in Plumula nelumbinis of CBFD may contribute to improving BPH condition by activating the relaxin signaling pathways.Communicated by Ramaswamy H. Sarma.

[Effects of Balanced Fertilization and Straw Mulching on Soil Nutrients and Stoichiometry in Purple Soil Slope].

To explore the effects of long-term balanced fertilization and straw mulching on soil nutrients and stoichiometric ratios in purple soil sloping cropland, nine plots (length 7 m×width 3 m) were established in Dianjiang County as the research sample area of long-term farmland nitrogen and phosphorus loss monitoring. The following three treatments were set up:conventional mode (CK), balanced fertilization mode (M1), and balanced fertilization+straw mulching mode (M2), with three replications for each treatment to compare the contents of carbon (C), nitrogen (N), phosphorus (P), and potassium (K) and their stoichiometric changes under different treatments from 2018 to 2020. The results showed:K contents showed significant differences among the three treatments in 2018, in the order of CK>M2>M1. NO3--N and NH4+-N contents showed significant differences among the three treatments in 2019, both in the order of M1>M2>CK. Other nutrient contents showed no significant difference among different treatments each year. Soil C and N contents showed non-significant differences among different years. The total K contents of CK, M1, and M2 in 2018 were significantly higher than that in other years and were 78.26% and 98.79%, 19.13% and 35.4%, and 54.49% and 41.76% higher than that in 2019 and 2020, respectively. The total P content in the CK and M2 treatments decreased with years, and that of CK and M2 in 2018 was 20.29% and 10.67% and 39.68% and 17.33% higher than that in 2019 and 2020, respectively. The available potassium (AK) content of the three treatments showed non-significant differences among different years, whereas the contents of nitrate nitrogen (NO3--N), ammonium nitrogen (NH4+-N), and available phosphorus (AP) showed significant differences among the different treatments, with all being the highest in 2020. Soil C:P, C:K, N:P, N:K, and P:K ratios of each treatment showed significant differences among different years (P<0.05). Soil C:K, N:K, and AN:AP ratios all showed significant differences among different fertilization modes in 2018 and 2019, respectively (P<0.05). There was a significantly linearly positive relationship between soil C and N concentration and soil P and K concentration. There were very significant linear positive correlations between soil C:K and C:P, N:K, N:P, and P:K; N:K with C:P, P:K, and N:P; and N:P with C:P, N:P, and C:P. Soil P concentration was highly significantly linearly negatively correlated with C:K and N:K ratios. There were significant positive correlations between soil NO3--N, NH4+-N, AN:AP, and AN:AK; NH4+-N, AN:AP, and AN:AK; and AN:AP and AN:AK. The results suggested that balanced fertilization and straw mulching was a more suitable management mode for purple soil sloping cropland.

Protein-coated cobalt oxide-hydroxide nanospheres deliver photosensitizer IR780 iodide for near-infrared light-triggered photodynamic/photothermal/chemodynamic therapy against colon cancer.

Phototherapy has garnered worldwide attention for its minimal invasiveness, controllability, and spatial selectivity in treating cancer. One promising approach involves the use of near-infrared dye IR780, which demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) effects under 808 nm laser irradiation. However, this hydrophobic dye's toxicity and limited tumor targeting ability severely hamper its suitability for cancer applications. Herein, a biocompatible nanoplatform CoOOH-IR780@BSA (CoIRB) is developed to efficiently deliver IR780 and provide multi-mode treatments for colon tumors. Due to the nanocarrier coating, CoIRB nanoparticles demonstrated reliable dispersion and stability, and their biotoxicity was substantially reduced for safer blood circulation, which overcame the biological barrier of IR780. The nanoplatform has also shown considerable results in phototherapy in vivo and in vitro experiments, with successful inhibition of MC38 tumor growth through intravenous administration. Additionally, the introduction of cobalt ions could induce Fenton-like reactions to activate the production of toxic hydroxyl radicals (˙OH), exerting an assisted chemodynamic therapy (CDT) effect. Notably, these nanodrugs also exhibited potential as scavengers of reductive glutathione (GSH) and hydrogen sulfide (H2S), leading to amplifying oxidative damage of reactive oxygen species (ROS). Overall, the versatile therapeutic platform, CoIRB, has opened up considerable prospects as a biotherapeutic option for combining PDT/PTT/CDT against colon cancer.

Proteins and signaling pathways response to Wenjingtongluo drug-contained serum in IHUVECs: an explorative proteomic study.

Angiogenesis is a dynamic and complex process leading to the development of new vessels from pre-existing vessels, which played a major role in pathological processes in many diseases. The present study aimed to investigate the effect of drug-contained serum of Traditional Chinese medicine (TCM) Wenjingtongluo decoction (WJLTD) on antiangiogenesis in Immortalized Human Umbilical Vascular Endothelial cells (IHUVECs), and elucidate the possible mechanisms based on proteomic analysis. Cells were treated with the drug-contained serum of the Drug-contained Serum (DS) of WJLTD and the blank serum (BS). The antiangiogenesis capacity of DS was evaluated using wound healing assay, Transwell, and tube formation assay. We performed three biological replicates to compare large-scale differential protein expression between two groups by tandem mass tag (TMT) labeling technology based on liquid chromatography-mass spectrometry analysis (LC-MS/MS). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed for the general characterization of overall enriched proteins. For validation of the results of TMT, the candidate proteins were verified by parallel reaction monitoring (PRM) analysis. The results showed that 4% DS could inhibit the migration process of IHUVECs according to wound healing assay and Transwell. And tube formation ability was also dramatically inhibited (p<0.001). TMT analysis revealed 148 differentially expressed proteins between two groups that were identified and quantified. The further validation results of the two candidate proteins, Ferritin heavy chain (FTH1) and Ferritin light chain (FTL) from the Ferroptosis pathway, which played an important role in DS treatment, were consistent with those of LC-MS/MS. In conclusion, this is the first proteomics-based study to report the mechanism underlying DS treatment for angiogenesis. Further functional verification of the potential signaling pathways and the enriched proteins is warranted.

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders.

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet-induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.

Effects of linseed oil supplementation duration on fatty acid profile and fatty acid metabolism-related genes in the muscles of Chinese crested white ducks.

Meat rich in polyunsaturated fatty acids is considered beneficial to health. Supplementing the diet with linseed oil promotes the deposition of polyunsaturated fatty acids (PUFAs) in poultry, a conclusion that has been confirmed multiple times in chicken meat. However, fewer studies have focused on the effects of dietary fatty acids on duck meat. Therefore, this study aims to evaluate the effects of the feeding time of a linseed oil diet on duck meat performance and gene expression, including meat quality performance, plasma biochemical indicators, fatty acid profile, and gene expression. For this study, we selected 168 Chinese crested ducks at 28 days old and divided them into three groups, with 56 birds in each group. The linseed oil content in the different treatment groups was as follows: the control group (0% flaxseed oil), the 14d group (2% linseed oil), and the 28d group (2% linseed oil). Ducks in the two experimental groups were fed a linseed oil diet for 28 and 14 days at 28 and 42 days of age, respectively. The results showed that linseed oil had no negative effect on duck performance (slaughter rate, breast muscle weight, and leg muscle weight) or meat quality performance (pH, meat color, drip loss, and shear force) (P > 0.05). The addition of linseed oil in the diet increased plasma total cholesterol and high-density lipoprotein cholesterol levels (P < 0.05), while decreasing triglyceride content (P < 0.05). Furthermore, the supplementation of linseed oil for four weeks affected the composition of muscle fatty acids. Specifically, levels of α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were increased (P < 0.05), while eicosatetraenoic acid content was negatively correlated with flaxseed oil intake (P < 0.05). qRT-PCR analysis further revealed that the expression of FATP1, FABP5, and ELOVL5 genes in the breast muscle, as well as FABP3 and FADS2 genes in the thigh muscle, increased after four weeks of linseed oil supplementation (P < 0.05). However, after two weeks of feeding, CPT1A gene expression inhibited fatty acid deposition, suggesting an increase in fatty acid oxidation (P < 0.05). Overall, the four-week feeding time may be a key factor in promoting the deposition of n-3 PUFAs in duck meat. However, the limitation of this study is that it remains unknown whether longer supplementation time will continue to affect the deposition of n-3 PUFAs. Further experiments are needed to explain how prolonged feeding of linseed oil will affect the meat quality traits and fatty acid profile of duck meat.

Hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally advanced gastric cancer after D2 radical resection: a randomized-controlled study.

BACKGROUND: Currently, there is a lack of an effective strategy for the prevention of peritoneal metastasis (PM) from locally advanced gastric cancer (AGC). This randomized-controlled study aimed to evaluate the outcome of D2 radical resection with hyperthermic intraperitoneal chemotherapy (HIPEC) plus systemic chemotherapy versus systemic chemotherapy alone in locally AGC patients. METHODS: All enrolled patients were randomly assigned to receive HIPEC plus systemic chemotherapy (HIPEC group) or systemic chemotherapy alone (non-HIPEC group) after radical gastrectomy. HIPEC was performed intraperitoneally with cisplatin (40 mg/m2) within 72 h after surgery, while systemic chemotherapy based on the SOX regimen (S-1 combined with oxaliplatin) was administered 4-6 weeks after radical surgery. Patterns of recurrence, adverse events, 3-year disease-free survival (DFS), and overall survival (OS) were analyzed. RESULTS: A total of 134 patients were enrolled in the present study. The 3-year DFS rate was 73.8% in the HIPEC group, which was significantly higher than that in the non-HIPEC group (61.2%, P = 0.031). The 3-year OS rate was 73.9% in the HIPEC group and 77.6% in the non-HIPEC group, with no significant difference (P = 0.737). PM was the most common distant metastasis in both groups. The occurrence rate of PM in the HIPEC group was statistically lower than that in the non-HIPEC group (20.9% vs. 40.3%, P = 0.015). Grade 3 or 4 adverse events occurred in 19 (14.2%) patients, and there was no significant difference between the two groups. CONCLUSION: Radical surgery followed by HIPEC combined with systemic chemotherapy is a safe and feasible strategy for locally AGC patients and could effectively improve DFS and reduce the occurrence of PM. However, more prospective randomized studies with a large sample size are warranted. TRIAL REGISTRATION: This study was registered with www.medresman.org.cn as ChiCTR2200055966 on 10/12/2016.

Effects of Variation in Tamarix chinensis Plantations on Soil Microbial Community Composition in the Middle Yellow River Floodplain.

Floodplains have important ecological and hydrological functions in terrestrial ecosystems, experience severe soil erosion, and are vulnerable to losing soil fertility. Tamarix chinensis Lour. plantation is the main vegetation restoration measure for maintaining soil quality in floodplains. Soil microorganisms are essential for driving biogeochemical cycling processes. However, the effects of sampling location and shrub patch size on soil microbial community composition remain unclear. In this study, we characterized changes in microbial structure, as well as the factors driving them, in inside- and outside-canopy soils of three patch sizes (small, medium, large) of T. chinensis plants in the middle Yellow River floodplain. Compared with the outside-canopy soils, inside-canopy had higher microbial phospholipid fatty acids (PLFAs), including fungi, bacteria, Gram-positive bacteria (GP), Gram-negative bacteria (GN), and arbuscular mycorrhizal fungi. The ratio of fungi to bacteria and GP to GN gradually decreased as shrub patch size increased. Differences between inside-canopy and outside-canopy soils in soil nutrients (organic matter, total nitrogen, and available phosphorus) and soil salt content increased by 59.73%, 40.75%, 34.41%, and 110.08% from small to large shrub patch size. Changes in microbial community composition were mainly driven by variation in soil organic matter, which accounted for 61.90% of the variation in inside-canopy soils. Resource islands could alter microbial community structure, and this effect was stronger when shrub patch size was large. The results indicated that T. chinensis plantations enhanced the soil nutrient contents (organic matter, total nitrogen, and available phosphorus) and elevated soil microbial biomass and changed microbial community composition; T. chinensis plantations might thus provide a suitable approach for restoring degraded floodplain ecosystems.

A multifunctional nanotheranostic agent based on Lenvatinib for multimodal synergistic hepatocellular carcinoma therapy with remarkably enhanced efficacy.

Lenvatinib (LT), a first-line molecular targeted therapeutic drug for hepatocellular carcinoma (HCC), has been replacing the status of Sorafenib (SF) as the clinically preferred and irreplaceable treatment for a decade. To overcome the low drug utilization and limited single efficacy of LT, ultrasmall copper sulfide nanocrystals (Cu2-xS NCs), and ultrasmall gold nanoparticle (AuNPs) were evenly wrapped into galactosamine conjugated poly(lactide-co-glycolide) (PLGA) as the drug delivery nanoparticles (CAL@PG) by nanoprecipitation. The CAL@PG NPs exhibited excellent stability under physiological conditions, whereas they released LT rapidly in the unique tumor microenvironment (TME) and high temperature, which could be provided by the near-infrared-II (NIR-II) photothermal effect of Cu2-xS NCs. Moreover, the temperature elevation, regenerated hydrogen peroxide (H2O2), and lower pH of TME could substantially boost the reaction potency of copper Fenton-like chemistry. More importantly, this combined therapy significantly improved the efficacy of LT, provided a multifunctional LT delivery system, and enriched the nanoparticle-augmented multimodal synergistic HCC therapy modality.

[Dryness-alleviating effect of processed Aurantii Fructus from Lingnan based on correlation of fecal metabolomics and dryness].

With the approach of untargeted metabolomics and correlation analysis, this study aimed to explore the mechanism of Aurantii Fructus from Lingnan region in alleviating dryness by analyzing the different effects of raw Aurantii Fructus(RAF) and processed Aurantii Fructus(PAF) on fecal endogenous metabolism in normal rats. Eighteen Sprague-Dawley(SD) rats were randomly divided into a control group(C), an RAF group(10 g·kg~(-1)), and a PAF group(10 g·kg~(-1)). After seven days of administration, the effects of RAF and PAF on dryness-related indexes were compared, including water intake, fecal water content, salivary secretion, the expression of AQP5, VIP, and 5-HT in the submandibular gland, as well as the expression of AQP3, VIP, and 5-HT in the colon. The fecal samples in each group were determined by LC-MS. Multivariate statistical analysis and Pearson correlation coefficient were used for screening the differential metabolites and metabolic pathways in alleviating dryness of RAF. The results indicated that both RAF and PAF showed certain dryness, and the dryness of RAF was more significant. Moreover, PAF could alleviate dryness of RAF to a certain extent by reducing the water intake, fecal water content, and the expression of AQP3, VIP, and 5-HT in the colon and increasing the salivary secretion and the levels of AQP5, VIP, and 5-HT in the submandibular gland. According to the analysis of fecal metabolomics, 99 and 58 metabolites related to dryness were found in RAF and PAF respectively, where 16 of them played an important role in alleviating dryness of RAF. Pathway analysis revealed that the mechanism of PAF in alleviating dryness of RAF was presumably related to the regulation of riboflavin metabolism, purine metabolism, arginine biosynthesis, pyrimidine metabolism, alanine metabolism, aspartate metabolism, glutamate metabolism, and retinol metabolism pathways. This study suggested that PAF might alleviate dryness of RAF by affecting the metabolic levels of the body, which provides a new basis for further clarifying the processing mechanism of PAF.

L-Ascorbic Acid 2-Phosphate Attenuates Methylmercury-Induced Apoptosis by Inhibiting Reactive Oxygen Species Accumulation and DNA Damage in Human SH-SY5Y Cells.

Methylmercury (MeHg) is a toxin that causes severe neuronal oxidative damage. As vitamin C is an antioxidant well-known to protect neurons from oxidative damage, our goal was to elucidate its protective mechanism against MeHg-induced oxidative stress in human neuroblastomas (SHSY5Y). We treated cells with MeHg, L-ascorbic acid 2-phosphate (AA2P), or both, and used MTT, flow cytometry, and Western blot analyses to assess cell damage. We found that MeHg significantly decreased the survival rate of SH-SY5Y cells in a time- and dose-dependent manner, increased apoptosis, downregulated PAR and PARP1 expression, and upregulated AIF, Cyto C, and cleaved Caspase-3 expression. A time course study showed that MeHg increased reactive oxygen species (ROS) accumulation; enhanced apoptosis; increased DNA damage; upregulated expression ofγH2A.X, KU70, 67 and 57 kDa AIF, CytoC, and cleaved Caspase-3; and downregulated expression of 116 kDa PARP1, PAR, BRAC1, and Rad51. Supplementation with AA2P significantly increased cell viability and decreased intrinsic ROS accumulation. It also reduced ROS accumulation in cells treated with MeHg and decreased MeHg-induced apoptosis. Furthermore, AA2P conversely regulated gene expression compared to MeHg. Collectively, we demonstrate that AA2P attenuates MeHg-induced apoptosis by alleviating ROS-mediated DNA damage and is a potential treatment for MeHg neurotoxicity.

Pollen-feeding behavior of diverse insects on Geranium delavayi, a flower with large, accessible pollen grains.

PREMISE: Why have pollen grains evolved to be exceptionally large in some species? Pollen-feeding hypothesis suggests that if the proportion of pollen amounts for feeding is reduced in a flower, the low allocation to pollen number would allow pollen grains to be larger. METHODS: To examine whether species with large pollen grains experience low pollen consumption, the behavior of insects feeding on nectar and pollen was observed and pollen transfer efficiency was estimated for four visitor types in Geranium delavayi. To see whether bees actively collected pollen, the numbers of grains in pollen baskets and on the body were compared. Both nutritional value (total protein and lipid) and chemical defense (phenolic metabolites) in pollen against pollen feeders were measured. RESULTS: Bumblebees and honeybees foraged for nectar, rarely groomed pollen into corbiculae, and had >5× higher pollen transfer efficiency than smaller solitary bees and flies, which were pollen eaters that removed more pollen but deposited less. Pollen grains were characterized by low protein and high lipid content with a low protein-lipid ratio, an unfavorable combination for bumblebees. Three secondary metabolites were significantly higher in pollen grains (7.77 mg/g) than in petals (1.08 mg/g) or in nectar (0.44 mg/g), suggesting stronger chemical defense in pollen. CONCLUSIONS: Our results indicated that large bees took nectar but little of the nutritionally poor and highly toxic pollen. These data support one prediction of the pollen-feeding hypothesis, that species with few and large pollen grains would also have low pollen-consumption rates.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

A Case-Control Study of the Effects of Implementing the Registered Nurses' Association of Ontario Guidelines for the Assessment and Management of Postoperative Pain and the Use of Relaxation Therapy in 312 Patients with Bone and Soft-Tissue Malignancy.

BACKGROUND The present study aimed to investigate the effects of implementing the Registered Nurses' Association of Ontario (RNAO) guidelines for the management of postoperative pain and the use of Jacobson's relaxation technique (JRT) in patients with bone and soft-tissue malignancy at a single center in China. MATERIAL AND METHODS A total of 312 patients were recruited and randomly divided into 2 groups. In the intervention group, the RNAO pain-management technique of JRT was adopted, while the control group received the standard institutional nursing management. Pain scores after the operation, according to the Numerical Rating Scale (NRS) combined with the Wong-Baker Faces Pain Rating Scale and Short-Form McGill Pain Questionnaire, were compared between the 2 groups. Nursing satisfaction was compared as well. RESULTS At 6, 24, and 72 h after the operation, the NRS scores combined with the Wong-Baker Faces Pain Rating Scale in the intervention group were significantly lower than those in the control group (P<0.001); 72 h after the operation, the Pain Rating Index, Visual Analogue Scale, present pain intensity, and total scores for the intervention group were significantly lower than those for the control group (P<0.001 for all 4 scores). The scores reported from the patients for nursing response and consequent care (P<0.001), nursing competence (P=0.029), and surgical pain-control satisfaction (P<0.001) in the intervention group were also significantly higher than those in the control group. CONCLUSIONS JRT can improve postoperative pain-control and nursing satisfaction in patients with malignant bone and soft-tissue tumors. These data suggest a benefit for application of JRT in clinical care.

Clinical Effect of Tongmai Fuming Decoction on Neovascular Ophthalmopathy.

Background: The incidence of neovascular eye disease is increasing year by year, seriously threatening human vision health and becoming an urgent public health problem. Tongmai fuming decoction as an experienced prescription can treat ischemic eye disease. Objective: To investigate the therapeutic effect of Tongmai fuming decoction combined with anti-VEGF therapy on neovascular ophthalmopathy. Methods: 52 patients (62 eyes) with neovascular ophthalmopathy who met the inclusion criteria from January 2018 to July 2020 were randomly divided into the control and observation groups. The control group was given an intravitreal injection of antivascular endothelial growth factor (VEGF) drugs once a day combined with on-demand treatment. The observation group was treated with traditional Chinese medicine Tongmai fuming decoction in addition to the treatment of anti-VEGF drugs. The best-corrected visual acuity (BCVA) was examined before and after treatment, and optical coherence tomography angiography (OCTA) was used to examine the mean retinal thickness and neovascularization in the macular area. Patients were followed for one year and the number of anti-VEGF injections was recorded. Results: After treatment, the average thickness of BCVA and macular retina in the two groups significantly improved. The BCVA of the control group was 0.59 ± 0.39 3 months after treatment, and that of the experimental group was 0.42 ± 0.25 3 months after treatment. The average thickness of the macular retina in the control group was 304.8 ± 79.7 3 months after treatment, and that in the experimental group was 267.7 ± 64.6 3 months after treatment; The average number of injections of anti-VEGF therapy in the control group was 2.32 ± 1.15 times, and that in the experimental group was 1.74 ± 0.76 times. There was a significant difference between the two groups. Conclusion: Tongmai fuming decoction and anti-VEGF therapy have a synergistic effect in the treatment of neovascular ophthalmopathy, which can reduce the treatment times of anti-VEGF drugs.

Photoaffinity Labeling-Based Chemoproteomic Strategy Reveals RBBP4 as a Cellular Target of Protopanaxadiol against Colorectal Cancer Cells.

Protopanaxadiol (PPD), a main ginseng metabolite, exerts powerful anticancer effects against multiple types of cancer; however, its cellular targets remain elusive. Here, we synthesized a cell-permeable PPD probe via introducing a bifunctional alkyne-containing diazirine photo-crosslinker and performed a photoaffinity labeling-based chemoproteomic study. We identified retinoblastoma binding protein 4 (RBBP4), a chromatin remodeling factor, as an essential cellular target of PPD in HCT116 colorectal cancer cells. PPD significantly decreased RBBP4-dependent trimethylation at lysine 27 of histone H3 (H3K27me3), a crucial epigenetic marker that correlates with histologic signs of colorectal cancer aggressiveness, and PPD inhibition of proliferation and migration of HCT116 cells was antagonized by RBBP4 RNA silencing. Collectively, our study highlights a previously undisclosed anti-colorectal cancer cellular target of the ginseng metabolite and advances the fundamental understanding of RBBP4 functions via a chemical biology strategy.

Multifunctional phototheranostic nanoplatform based on polydopamine-manganese dioxide-IR780 iodide for effective magnetic resonance imaging-guided synergistic photodynamic/photothermal therapy.

Multifunctional phototheranostics combining diagnostic and therapeutic modalities may provide a revolutionary opportunity for cancer treatment. As a promising tumor phototheranostic molecule, IR780 iodide (IR780) shows excellent photodynamic and photothermal performance under near-infrared laser irradiation; however, its hydrophobicity and instability limit its further use in organisms. This work demonstrates the design and development of a multifunctional nanoplatform (PMIDA, referring to polydopamine (PDA)-manganese dioxide (MnO2)-IR780) for imaging-guided phototherapy. The good biocompatibility of PDA greatly improves the water solubility and photostability of IR780, and its excellent photothermal properties make PMIDA a dual photothermal therapy (PTT). MnO2-induced generation of oxygen in the tumor microenvironment improves the hypoxia effect and photodynamic therapy (PDT) of IR780. Moreover, Mn2+ serves as a decent T1-weighted magnetic resonance imaging (MRI) probe to guide treatment. Notably, in relevant cellular assays, PMIDA shows high photodynamic and photothermal effects contributing to the final therapeutic effect. The MRI-guided PDT/PTT synergistic therapy effect in vivo is demonstrated by precise tumor diagnosis and complete tumor elimination outcomes. Based on these experiments, PMIDA nanoparticles display promising effects in facilitating intravenous injection of IR780 and achieving magnetic resonance imaging (MRI)-guided phototheranostic efficacy for tumor treatment.