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Purpose. To explore the clinical application of Baihe Dihuang Decoction. To provide certain data support and theoretical basis for the clinical application of Baihe Dihuang Decoction in the future. Methods. With “Baihe Rehmannia Tang” as the search term, the search was carried out on CNKI, VIP, Wanfang, PubMed and other databases. The statistical analysis of Baihe Dihuang decoction for treating diseases was obtained. Meta-analysis of the data was performed using RevMan 5.3 software to analyze the main therapeutic indicators of the disease. Results. According to the 83 valid literature that can be found, it is shown that 17 are used for the treatment of depression, 14 are used for the treatment of menopausal syndrome, 24 are used for the treatment of insomnia, and 28 are used for the treatment of other diseases. Conclusion. In the treatment of depression, menopausal syndrome, and insomnia combined with Baihe Dihuang Decoction can have a better therapeutic effect and diminish the incidence of adverse reactions. It provides a theoretical basis for the study and experimental study of its active components.

The recent rapid development in the field of extracellular vesicles (EVs) based nanotechnology has provided unprecedented opportunities for nanomedicine platforms. As natural nanocarriers, EVs such as exosomes, exosome-like nanoparticles and outer membrane vesicles (OMVs), have unique structure/composition/morphology characteristics, and show excellent physical and chemical/biochemical properties, making them a new generation of theranostic nanomedicine. Here, we reviewed the characteristics of EVs from the perspective of their formation and biological function in inflammatory bowel disease (IBD). Moreover, EVs can crucially participate in the interaction and communication of intestinal epithelial cells (IECs)-immune cells-gut microbiota to regulate immune response, intestinal inflammation and intestinal homeostasis. Interestingly, based on current representative examples in the field of exosomes and exosome-like nanoparticles for IBD treatment, it is shown that plant, milk, and cells-derived exosomes and exosome-like nanoparticles can exert a therapeutic effect through their components, such as proteins, nucleic acid, and lipids. Moreover, several drug loading methods and target modification of exosomes are used to improve their therapeutic capability. We also discussed the application of exosomes and exosome-like nanoparticles in the treatment of IBD. In this review, we aim to better and more clearly clarify the underlying mechanisms of the EVs in the pathogenesis of IBD, and provide directions of exosomes and exosome-like nanoparticles mediated for IBD treatment.

As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (

Plant-derived exosome-like nanoparticles (PDENs) have been paid great attention in the treatment of ulcerative colitis (UC). As a proof of concept, we show that Portulaca oleracea L-derived exosome-like nanoparticles (PELNs) are isolated and identified from edible Portulaca oleracea L with desirable nano-size (~ 160 nm) and a negative zeta potential value (-31.4mV). Moreover, we find that oral administration of PELNs can suppress the expressions of pro-inflammation cytokines (TNF-α, IL-6, IL-12, and IL-1β), and increase the levels of anti-inflammatory cytokine (IL-10) in dextran sulphate sodium (DSS)-induced mice and PHLPP2−/− mice spontaneous colitis contributing to alleviate colitis. Furthermore, orally administered PELNs can display great stability in gastrointestinal tract environment, and specifically targeted to desired inflammatory site in mice colitis. In addition, oral administration of PELNs can effectively maintain the diversity and balance of gut microbiota, and specifically induce the differentiation of double-positive CD4+CD8+T cells (DP CD4+CD8+T cells). In summary, our findings suggest that orally administered PELNs brings a novel and natural colon-targeted agent, and open a new therapeutic avenue in the management of UC.

[Zn(3-tba)2], 1, a 1-D coordination polymer synthesised as 1 DMA, 1α, transformed to a nonporous form, 1β, upon activation. 1β underwent further transformation to the dimeric complex [Zn(3-tba)2(H2O)2], 2, above 40% RH. The reverse transformations, 2 to 1β and 1β to 1α, were accomplished by heating and exposure to DMA, respectively, and were single-crystal-to-single-crystal phase changes. Single crystal X-ray diffraction revealed that the second transformation resulted from Zn–carboxylate bond breakage and concomitant coordination of water molecules. Other solvent molecules did not induce a phase change

To investigate the efficacy, safety, and mechanism of topical application of aloe vera gel (AVG) to treat diabetic chronic cutaneous ulcers in Bama miniature pigs.The Bama miniature pig model of diabetic chronic skin wounds was constructed and the model pigs were randomly assigned to AVG daily administration group (AVG QD), aloe vera gel every-other-day administration group (AVG QOD), and diabetic control group (DC). A non-diabetic chronic skin wounds model pig was set as the non-diabetic control group (NDC). Treatment efficacy was evaluated based on the amount of time needed for complete healing of the wounds, healing rates, granulation growth rates, and skin histopathological changes. Safety was evaluated according to whether adverse reactions were observed. In addition, the dynamic changes of the relative expression levels of miR21, miR29a, miR126, miR146a, miR155, and miR210 in wound granulation tissues were examined.1) Efficacy and safety: The amount of time needed for complete healing of the wounds was shorter in the NDC group than those of the three other groups, DC group, AVG QD group, and AVG QOD group (allAVG topical application can shorten the time needed for complete healing of diabetic chronic wounds in Bama minipigs. The wound healing speed of the alternate-day treatment group was faster than that of the daily treatment group. No adverse reactions were observed over the course of the treatment. The mechanism may be related to the up-regulation of the expressions of miR21, miR126, and miR210 and the down-regulation of miR29a and miR155 in wound granulation tissue.

The construction of carbon-heteroatom bonds is one of the most active areas of research in organic chemistry because the function of organic molecules is often derived from the presence of heteroatoms. Although considerable advances have recently been achieved in radical-involved catalytic asymmetric C-N bond formation, there has been little progress in the corresponding C-O bond-forming processes. Here, we describe a photoinduced copper-catalyzed cross-coupling of readily available oxime esters and 1,3-dienes to generate diversely substituted allylic esters with high regio- and enantioselectivity (>75 examples; up to 95% ee). The reaction proceeds at room temperature under excitation by purple light-emitting diodes (LEDs) and features the use of a single, earth-abundant copper-based chiral catalyst as both the photoredox catalyst for radical generation and the source of asymmetric induction in C-O coupling. Combined experimental and density functional theory (DFT) computational studies suggest the formation of π-allylcopper complexes from redox-active oxime esters as bifunctional reagents and 1,3-dienes through a radical-polar crossover process.

The Ir

Atom transfer radical addition (ATRA) reaction of alkenes has had a tremendous impact on the field of radical difunctionalizations of alkenes. Particularly in the three-component photo-ATRA-type processes, a rich chemical space and structural diversity could be achieved by smart combination of redox-active radical precursors and the third coupling components (e.g., halides, C-, N-, and O-nucleophiles) under mild con-ditions. However, the inherent complicated mechanisms involving radical chain or outer-sphere SET of the incipient radical intermediates render dearth of general catalytic methods for highly enantioselective variants, especially these regarding asymmetric intermolecular C-O bond formation. Here, we report a visible-light-induced copper-catalyzed asymmetric three-component photo-ATRA-type reaction of alkenes with oxime esters and carboxylic acids. In this process, a highly enantioselective intermolecular C-O cross-coupling between incipient sp3-hybridized carbon radicals and carboxylic acids was enabled by aryl π-bond-engaged [σ + π]-copper complex. This three-component photo-ATRA-type reaction exhibits broad substrate scope and high functional group tolerance with respect to each component, giving the desired cross-coupled products with generally good yields and excellent enantioselectivity (>70 examples; up to 97% ee). Combined experimental and computational studies are also performed to gain insight into the mechanism. This finding provides a new platform for the development of other enantioselective benzylic-type radical-based cross-coupling reactions.

A three-dimensional (3D) metal–organic framework [(CH3)2NH2][Zn2(DMTDC)2(3-mtz)]·4DMF·3H2O (Zn-MOF) has been solvothermally synthesized by using mixed ligands of 3-methyl-1,2,4-triazole (3-Hmtz) and a thiophene-functionalized dicarboxylate ligand, 3,4-dimethylthieno[2,3-b]thiophene-2,5-dicarboxylic acid (H2DMTDC). Zn-MOF exhibits a uninodal 6-connected pcu α-Po topology structure and possesses an anionic framework with large 1D-trapezoidal channels. Gas adsorption studies reveal that the activated Zn-MOF-a displays selective adsorption of CO2 over N2 at 273 K and 298 K as well as a high isosteric heat of CO2 adsorption. Moreover, Zn-MOF shows selective adsorption of the cationic dyes over the anionic and neutral dyes, and can be used as a fast-response and sensitive probe for the detection of Fe3+ by fluorescence quenching after encapsulation of Tb3+ into the pores by postsynthetic cation exchange.

As a main digestive organ and an important immune organ, the intestine plays a vital role in resisting the invasion of potential pathogens into the body. Intestinal immune dysfunction remains important pathogenesis of inflammatory bowel disease (IBD). In this review, we explained the interactions among symbiotic flora, intestinal epithelial cells, and the immune system, clarified the operating mechanism of the intestinal immune system, and highlighted the immunological pathogenesis of IBD, with a focus on the development of immunotherapy for IBD. In addition, intestinal fibrosis is a significant complication in patients with long-term IBD, and we reviewed the immunological pathogenesis involved in the development of intestinal fibrogenesis and provided novel antifibrotic immunotherapies for IBD.

Polyoxometalates (POMs) have a broad array of applied platforms with well-characterized catalysis including photocatalysis to achieve aliphatic C(sp

Background Permethrin is one of the pyrethroid insecticides, which is widely used in agriculture and public health. Although acute toxicity of the insecticide has been studied, the chronic toxicity upon the long-term exposure has not been clear yet. The purpose of the current study is to investigate the organ toxicities of permethrin following its long-term low-dose exposure. Methods Male Wistar rats were daily administrated orally with permethrin (75 mg/kg body weight/day, gavage) for 90 days, and then the samples of biofluids (blood and urine) and organs including liver and kidney were collected. The serum and urine samples were measured by biochemical assay and the tissues of kidney and liver were examined and analyzed by histopathological method. Results The results showed that no change was found in serum and urine biochemical parameters for the toxicity; however, significant changes including hyperchromatic nuclei swollen in the hepatic parenchymal cells and the swelling proximal tubules in the kidneys were observed in the tissue structures of liver and kidneys in the histopathological sections. Conclusion These results indicate that low-dose long-term exposure of permethrin can cause chronic toxicity with slight liver and kidney damage.

Background This study aims to establish an in vitro monitoring approach to evaluate the pesticide exposures. We studied the in vitro cytotoxicity of three different body fluids of rats to the respective corresponding tissue-derived cells. Methods Wistar rats were orally administrated daily with three different doses of chlorpyrifos (1.30, 3.26, and 8.15 mg/kg body weight/day, which is equal to the doses of 1/125, 1/50, and 1/20 LD50, respectively) for consecutive 90 days. Blood samples as well as 24-hour urine and fecal samples were collected and processed. Then, urine, serum, and feces samples were used to treat the correspondent cell lines, i.e., T24 bladder cancer cells, Jurkat lymphocytes, and HT-29 colon cancer cells respectively, which derived from the correspondent tissues that could interact with the respective corresponding body fluids in organism. Cell viability was determined by using MTT or trypan blue staining. Results The results showed that urine, serum, and feces extract of the rats exposed to chlorpyrifos displayed concentration- and time-dependent cytotoxicity to the cell lines. Furthermore, we found that the cytotoxicity of body fluids from the exposed animals was mainly due to the presence of 3, 4, 5-trichloropyrindinol, the major toxic metabolite of chlorpyrifos. Conclusions These findings indicated that urine, serum, and feces extraction, especially urine, combining with the corresponding tissue-derived cell lines as the in vitro cell models could be used to evaluate the animal exposure to pesticides even at the low dose with no apparent toxicological signs in the animals. Thus, this in vitro approach could be served as complementary methodology to the existing toolbox of biological monitoring of long-term and low-dose exposure to environmental pesticide residues in practice.

A 76 year-old woman with 8-year history of diabetes mellitus and hypertension was admitted with gangrene of left great toe, 3rd, 4th and 5th toes. Twenty months ago, She started to receive hemodialysis due to end-stage renal disease. She did not have any history of reactive airway disease nor bradycardia that would contraindicate the use of topical beta-blocker. The X-ray of left lower limb and foot showed calcification of left superficial femoral artery, popliteal artery, anterior tibial artery, posterior tibial artery, dorsal foot artery and digital artery, as well as osteolytic destruction at distal end of metatarsal bone, and lateral dislocation of the 4th and 5th toes. Color Doppler ultrasound of bilateral lower extremity arteries showed obvious calcification of bilateral superficial femoral arteries, thrombosis of left popliteal artery, severe stenosis of left anterior tibial artery, occlusion of left posterior tibial artery, right anterior tibial artery and posterior tibial artery. Computed tomographic angiography (CTA) of bilateral lower limb arteries revealed moderate stenosis of left superficial femoral artery, occlusion of left popliteal artery, left posterior tibial artery and dorsal pedal artery, occulusion of right posterior tibial artery, but right dorsal pedal artery was visible.Diagnosis of diabetic foot (left, grade 4) and diabetic lower extremity arterial occlusion (left, stage 4) was made. Based on multidisciplinary team (MDT) discussion, the patient was unable to undergo vascular bypass surgery, and left lower extermity amputation also was not suitable because of right atrial thrombosis. Therefore, conservative treatment was recommended. The specific scheme used clopidogrel for antiplatelet agglutination, Low Molecular Weight Heparin (Clexane) and warfarin for anticoagulation, lipo-alprostadil for vasodilation, as well as local debridement and ultrasonic debridement. The treatments were given for up to 9 weeks, but with no significant clinical response. So the patient was treated with vacuum-assisted closure and autologous platelet-rich gel therapy for the next 7 weeks, then applied with 1 drop of timolol maleate 0.5% ophthalmic solution per cm

Meloidogyne enterolobii, an aggressive plant-parasitic nematode, has been causing great yield loss worldwide in recent years. With no resistant Chinese cabbage cultivar available currently, a biological control strategy is needed to offer an eco-friendly option for sustainable farming. In this study, the nematode suppression efficacy of two newly isolated fungi, Paraboeremia taiwanensis and Samsoniella sp., were evaluated against M. enterolobii and compared to the known biological control agents Hyalorbilia oviparasitica strain DoUCR50 and Purpureocillium lilacinum strain 251 (PL251). Both P. taiwanensis and Samsoniella sp. reduced 29%&ndash, 63% disease severity as effectively as the commercial product PL251 on Chinese cabbage in greenhouse trails. The in vitro egg infection rate was 47.83% by P. taiwanensis and 47.50% for Samsoniella sp., respectively. A special protocol for scanning electron microscope observation of the fungi-infected nematodes was established in this study, and the egg parasitism of the four fungi against M. enterolobii was further confirmed. For all fungi examined in this study, fungal hyphae were seen apparently penetrating into M. enterolobii eggs without destructive damage of the overall outer eggshell and the hyphae continued to grow within eggs after 6 days of infection. The results of this study imply a similar egg-parasitism mechanism for P. taiwanensis, Samsoniella sp., H. oviparasitica DoUCR50, and P. lilacinum PL251. It further enlightens the application potential of nematophagous fungi as biocontrol agents against plant-parasitic nematodes in vegetable crop management.

Carbamates and pyrethroids are widely used pesticides. However, their joint toxicity at low doses with long-term exposure remains unknown. Therefore, we investigated the subchronic joint hepatotoxicity of the two representative pesticides within these two classes, i.e., propoxur (PR) and permethrin (PE) in rats. The male Wistar rats were orally treated with three different doses of PR, PE and their mixtures for 90 consecutive days. Liver weight, serum clinical chemistry parameters and histopathological changes were measured to access the hepatotoxicity. In addition, oxidative stress markers in liver were measured using biochemical assays. The results showed that PR reduced liver weight and lead to prominent liver histological changes. Moreover, PR dose-dependently induced lipid peroxidation and reduced superoxide dismutase activity. In contrast, PE induced a relatively mild hepatotoxicity. Intriguingly, the mixture of PR and PE did not reduce liver weight or increase serum aspartate transaminase activity. In addition, the mixture did not reduce the antioxidant enzyme activity as PR did. Thus, these results showed that PR induced prominent hepatotoxicity with subchronic exposure, and there is a potential antagonistic interaction between PR and PE on the oxidative damage in liver of rats.

Background: Permethrin is a type of widely used pyrethroid pesticide. Although acute toxicity of permethrin has been well-characterised, the non-acute toxicity of permethrin upon long-term ...

As a major kind of carbamate insecticide, propoxur plays an important role in agriculture, veterinary medicine, and public health. The acute toxicity of propoxur is mainly neurotoxicity due to the inhibition of cholinesterase. However, little is known regarding the toxicity of propoxur upon long-term exposure at low dose. In this study, Wistar rats were orally administrated with low dose (4.25 mg/kg body weight/day) for consecutive 90 days. And the urine samples in rats treated with propoxur for 30, 60, and 90 days were collected and analyzed by employing 1H NMR-based metabolomics approach. We found that propoxur caused significant changes in the urine metabolites, including taurine, creatinine, citrate, succinate, dimethylamine, and trimethylamine-N-oxide. And the alteration of the metabolites was getting more difference compared with that of the control as the exposure time extending. The present study not only indicated that the changed metabolites could be used as biomarkers of propoxur-induced toxicity but also suggested that the time-course alteration of the urine metabolomic profiles could reflect the progressive development of the toxicity following propoxur exposure.

Inflammation and desmoplasia are frequently identified in the tumor microenvironment, and have been demonstrated to be effective modulators of malignant biological events. However, the mechanisms by which the inflammatory microenvironment and interstitial fibrosis interact with one another remain to be elucidated. The present study aimed to investigate the degree of inflammation and interstitial fibrosis in tongue squamous cell carcinoma (TSCC), and how this acts to affect the outcome of TSCC. Tissue samples from 93 cases of TSCC and paired tumor-adjacent non-neoplastic tongue epithelium, as well as 14 cases of epithelial dysplasia, were used. Interstitial collagen fibers were assessed using Masson's trichrome stain. Immunohistochemical identification of cancer-associated fibroblasts (CAFs) and stroma-infiltrating B cells was performed via detection of α-smooth muscle actin (SMA), vimentin, desmin and cluster of differentiation 19 (CD19). The clinicopathological significance and overall survival of the TSCC patients were statistically analyzed. Regularly distributed CAFs and CD19+ B cells were identified in the TSCC stroma, whereas no CAFs or CD19+ B cells were observed in epithelial dysplasia samples or paired tumor-adjacent non-neoplastic tongue epithelium samples. The distribution of interstitial collagen fibers and CAFs was closely associated with the tumor stage of the primary cancer, and high levels of CD19+ B cells together with low CAF infiltration were identified to be associated with favorable prognosis in TSCC. In conclusion, the inflammatory and interstitial fibrotic microenvironments coexist in TSCC, and each has specific effects on disease outcome, individually or perhaps collectively. However, it remains to be determined exactly how the microenvironments affect one another in TSCC.

Organophosphates and pyrethroids are widely used pesticides with prominent toxicity to humans. However, their joint toxicity has not been thoroughly investigated. In this study, we investigated the oxidative damages induced by low dose dichlorvos (DDVP) and deltamethrin (DM), the representative organophosphate and pyrethroid, respectively, and their mixtures in the liver of rats for 90 consecutive days. Two oxidative stress markers, malondialdehyde (MDA) and protein carbonyl (PCO) levels, were measured to reflect the extent of lipid peroxidation and protein oxidation, respectively. DDVP, DM, and their mixtures induced levels of MDA and PCO dose-dependently, although no toxic signs and pathological changes of liver were found in the rats following 90-day exposure. DDVP and DM induced greater increase of MDA than PCO, which indicated that lipids were particularly sensitive to the oxidative damage. We found that DDVP, DM and their mixtures could inhibit the activity of two antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). The effects of DM on SOD activity, lipid peroxidation and protein oxidation were greater than those of DDVP. The combined effect of DDVP and DM was lower than the sum of their individual effects. Thus the interaction between dichlorvos and deltamethrin may be antagonistic on the induction of oxidative stress in rat liver.

Organophosphorus (OP) and carbamate (CM) pesticides are widely used in agriculture. These pesticides are highly toxic to humans and their residues in food pose potential threat to human health. In this study, we investigated the effect of subchronic low-level exposure of OPs (dichlorvos, DDVP; malathion, MAL), CM pirimicarb (PI), or their mixtures (DDVP+MAL, DDVP+PI) on mice liver. Metabonomic analysis based on (1)H nuclear magnetic resonance spectroscopy was carried out in combination with biochemical assays. Serum metabonomic analysis showed that levels of trimethylamine-N-oxide, lactate, acetone, very low- and low-density lipoprotein and 3-hydroxybutyrate changed after exposure to the pesticides. In the liver extracts, lactate, glucose, choline, glutathione, alanine, glutamine and isoleucine levels changed after the treatment by pesticides. Our results indicated that exposure to low dose DDVP, MAL and PI, either alone or in combination lead to alteration of liver glucose, fat and protein metabolism, energy metabolism and oxidative balance. This study also showed that metabonomics is of potential use in food toxicity study.

We used a simple low-temperature hydrothermal approach to synthesize Ag nanoparticles (NPs) and demonstrated their efficiency as organic molecule detectors in surface enhanced Raman Scattering (SERS). Using finite difference time domain simulation, we described an investigation on the distribution of electric fields amplitude of the neighboring Ag NPs. The enhanced electric field is confined at the interparticle gaps and the enhancement factor can be further increased with reducing the spacing between the NPs. The theoretical simulation demonstrated good consistency with the experimental measurement results, which predicts an electric fields amplitude enhancement of 115 at the center of NPs gap and an electromagnetic SERS enhancement of 108. The evidence of clear correlations between SERS enhancement and morphology distribution offer a route to develop more effective SERS substrates.

Anticholinesterase pesticides have been widely used in agricultural and domestic settings and can be detected in the environment after long-term use. Although the acute toxic effects of chlorpyrifos and carbaryl have been well described, little is known about the chronic toxicity of the pesticides mixture. To investigate their chronic neurotoxicity, Wistar rats were exposed to chlorpyrifos, carbaryl, and their mixture (MIX) for 90 consecutive days. The activities of serum cholinesterase (ChE) as well as acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in nerve tissues were determined. Furthermore, the histopathological examination was carried out. The results showed that ChE activity significantly decreased in all treated rats except the rats treated with low dose carbaryl. Treatment with middle- and high-dose chlorpyrifos and MIX in rats significantly inhibited AChE activity in the central nervous tissues, whereas treatment with carbaryl alone did not. In sciatic nerve, AChE activity was significantly inhibited by high-dose carbaryl and MIX, but not by chlorpyrifos alone. No significant NTE inhibition was observed in all treatment groups. Histopathological examination revealed that both chlorpyrifos and MIX treatment induced hippocampal damage. However, no obvious hippocampal damage was found in carbaryl-treated rats. Carbaryl and MIX, but not chlorpyrifos alone, induced pathological damage of sciatic nerve. Taken together, all of the results indicated that chlorpyrifos and carbaryl have different toxicological target tissues in nervous system and showed corresponding effects in the nervous tissues, which may reflect the different sensitivity of central and peripheral nervous tissues to different pesticides individually and in combination.

In this paper, a multiple output switched capacitor (SC) DC-DC converter with capacitor sharing technique is proposed for event-driven energy-efficient sensor-fusion platforms. The converter is able to convert 1.2V supply voltage to five different output voltages ranging from 0.44V to 2.2V to power different building blocks in the system. A part of the flying capacitor can be shared between five SC cells according to the loading condition to reduce the chip area. With capacitor sharing concept, 36% of on-chip metal-insulator-metal (MIM) capacitor can be reduced. The proposed switched capacitor DC-DC converter is implemented by TSMC 90nm CMOS process. The simulation results show the converter achieves 80% maximum conversion efficiency with less than 20mV output ripple.