Mulberry Leaf-Derived Morin Activates ß-Catenin by Binding to Frizzled7 to Promote Intestinal Stem Cell Expansion upon Heat-Stable Enterotoxin b Injury.

Intestinal stem cells (ISCs) sustain epithelial renewal by dynamically altering behaviors of proliferation and differentiation in response to various nutrition and stress inputs. However, how ISCs integrate bioactive substance morin cues to protect against heat-stable enterotoxin b (STb) produced by Escherichia coli remains an uncertain question with implications for treating bacterial diarrhea. Our recent work showed that oral mulberry leaf-derived morin improved the growth performance in STb-challenged mice. Furthermore, morin supplementation reinstated the impaired small-intestinal epithelial structure and barrier function by stimulating ISC proliferation and differentiation as well as supporting intestinal organoid expansion ex vivo. Importantly, the Wnt/ß-catenin pathway, an ISC fate commitment signal, was reactivated by morin to restore the jejunal crypt-villus architecture in response to STb stimulation. Mechanically, the extracellular morin-initiated ß-catenin axis is dependent or partially dependent on the Wnt membrane receptor Frizzled7 (FZD7). Our data reveal an unexpected role of leaf-derived morin, which represents molecular signaling targeting the FZD7 platform instrumental for controlling ISC regeneration upon STb injury.

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).

Heat stress disrupts intestinal stem cell migration and differentiation along the crypt-villus axis through FAK signaling.

During heat stress (HS), the intestinal epithelium suffers damage due to imbalance of tissue homeostasis. However, the specific mechanism by which intestinal stem cells (ISCs) migrate and differentiate along the crypt-villus axis to heal lesions upon insult is unclear. In our study, C57BL/6 mice and IPEC-J2 cells were subjected to normal ambient conditions (25 °C for 7 days in vivo and 37 °C for 18 h in vitro) or 41 °C. The results showed that HS impaired intestinal morphology and barrier function. The numbers of ISCs (SOX9+ cells), mitotic cells (PCNA+ cells), and differentiated cells (Paneth cells marked by lysozyme, absorptive cells marked by Villin, goblet cells marked by Mucin2, enteroendocrine cells marked by Chromogranin A, and tuft cells marked by DCAMKL1) were reduced under high temperature. Importantly, BrdU incorporation confirmed the decreased migration ability of jejunal epithelial cells exposed to 41 °C. Furthermore, intestinal organoids (IOs) expanded from jejunal crypt cells in the HS group exhibited greater growth disadvantages. Mechanistically, the occurrence of these phenotypes was accompanied by FAK/paxillin/F-actin signaling disruption in the jejunum. The fact that the FAK agonist ZINC40099027 reversed the HS-triggered inhibition of IPEC-J2 cell differentiation and migration further confirmed the dominant role of FAK in response to high-temperature conditions. Overall, the present investigation is the first to reveal a major role of FAK/paxillin/F-actin signaling in HS-induced ISC migration and differentiation along the crypt-villus axis, which indicates a new therapeutic target for intestinal epithelial regeneration after heat injuries.

Highly flexible and superhydrophobic MOF nanosheet membrane for ultrafast alcohol-water separation.

High-performance pervaporation membranes have potential in industrial separation applications, but overcoming the permeability-selectivity trade-off is a challenge. We report a strategy to create highly flexible metal-organic framework nanosheet (MOF-NS) membranes with a faveolate structure on polymer substrates for alcohol-water separation. The controlled growth followed by a surface-coating method effectively produced flexible and defect-free superhydrophobic MOF-NS membranes. The reversible deformation of the flexible MOF-NS and the vertical interlamellar pathways were captured with electron microscopy. Molecular simulations confirmed the structure and revealed transport mechanism. The ultrafast transport channels in MOF-NS exhibited an ultrahigh flux and a separation factor of 8.9 in the pervaporation of 5 weight % ethanol-water at 40°C, which can be used for biofuel recovery. MOF-NS and polydimethylsiloxane synergistically contribute to the separation performance.

Formation of Super-Assembled TiOx /Zn/N-Doped Carbon Inverse Opal Towards Dendrite-Free Zn Anodes.

Uncontrolled growth of Zn dendrites and side reactions are the major restrictions for the commercialization of Zn metal anodes. Herein, we develop a TiOx /Zn/N-doped carbon inverse opal (denoted as TZNC IO) host to regulate the Zn deposition. Amorphous TiOx and Zn/N-doped carbon can serve as the zincophilic nucleation sites to prevent the parasitic reactions. More importantly, the highly ordered IO host homogenizes the local current density and electric field to stabilize Zn deposition. Furthermore, the three-dimensional open networks could regulate Zn ion flux to enable stable cycling performance at large current densities. Owing to the abundant zincophilic sites and the open structure, granular Zn deposits could be realized. As expected, the TZNC IO host guarantees the steady Zn plating/stripping with a long-term stability over 450 h at the current density of 1 mA cm-2 . As a proof-of-concept demonstration, a TZNC@Zn||V2 O5 full cell shows long lifespan over 2000 cycles at 5.0 A g-1 .

Lauric acid alleviates deoxynivalenol-induced intestinal stem cell damage by potentiating the Akt/mTORC1/S6K1 signaling axis.

Intestinal stem cell (ISC)-driven intestinal homeostasis is subjected to dual regulation by dietary nutrients and toxins. Our study investigated the use of lauric acid (LA) to alleviate deoxynivalenol (DON)-induced intestinal epithelial damage. C57BL/6 mice in the control, LA, DON, and LA + DON groups were orally administered PBS, 10 mg/kg BW LA, 2 mg/kg BW DON, and 10 mg/kg BW LA + 2 mg/kg BW DON for 10 days. The results showed that LA increased the average daily gain and average daily feed intake of the mice exposed to DON. Moreover, the DON-triggered impairment of jejunal morphology and barrier function was significantly improved after LA supplementation. Moreover, LA rescued ISC proliferation, inhibited intestinal cell apoptosis, and promoted ISC differentiation into absorptive cells, goblet cells, and Paneth cells. The jejunum crypt cells from the mice in the LA group expanded into enteroids, resulting in a significantly greater enteroid area than that in the DON group. Furthermore, LA reversed the DON-mediated inhibition of the Akt/mTORC1/S6K1 signaling axis in the jejunum. Our results indicated that LA accelerates ISC regeneration to repair intestinal epithelial damage after DON insult by reactivating the Akt/mTORC1/S6K1 signaling pathway, which provides new implications for the function of LA in ISCs.

[Characteristics and Sources of Microbial Aerosols in Urban and Mountainous Areas in Autumn and Winter in Xi'an, China].

To explore the bioaerosol composition characteristics and sources in urban areas and mountains, three sample sites were selected in urban (urban, suburban) and southern mountainous areas in Xi'an, and air, soil, and leaf samples were simultaneously collected. The fungi and bacteria community structures at different sampling sites were analyzed through a high-throughput sequencing method, and their spatio-temporal variations were also examined. Moreover, a source track technique was used to identify the source of microorganisms in the air. The results showed that the fungi and bacteria at different sampling sites were significantly different, indicating that the geographical location has a significant influence on the community structure of microorganisms in the air. In winter, more potential fungal pathogens and bacterial pathogens were detected in urban areas with high relative abundance and diversity. In addition, the results showed that the main local source of fungi and bacteria was the leaf surface, of which the contribution rate of bacteria in the air fine particles was up to (55±30)%. This study can provide a scientific basis for understanding the characteristics of microbial pollution in the atmosphere, and for air environment quality evaluation and disease prevention in China.

Recent progress of Ni-Fe layered double hydroxide and beyond towards electrochemical water splitting.

The electrochemical water splitting process including the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) is considered as one of the most promising methods for high-purity hydrogen production. Ni-Fe based compounds, especially Ni-Fe layered double hydroxide (LDH), have become highly efficient electrocatalysts to expedite the above reactions. During the last decade, great progress has been witnessed in the development of Ni-Fe based electrocatalysts. Diverse regulatory strategies such as morphology modulation, composition control, and defect engineering have been employed to optimize their electrochemical performances for water splitting. In addition, the family of Ni-Fe based compounds has been expanded from LDHs to alloys, sulfides, phosphides and so forth. Deep experimental investigations and theoretical studies have also been carried out to reveal the intrinsic origin of the superior electrocatalytic performances. In this review, we summarise the recent development of Ni-Fe based compounds for electrochemical water splitting with high efficiency. Special focus has been placed on the design principle and synthetic strategies of Ni-Fe based compounds. In the end, remaining challenges and future research directions are briefly discussed.

[Effect of exogenous selenium on accumulation and chemical forms of cadmium in cucumber (Cucumis satiuus L.)].

Pot experiments were carried out to investigate the influence of different selenium (Se) levels (0, 0.5 and 1.0 mg x L(-1)) on the plant growth, concentration of malonaldehyde (MDA), activities of antioxidant enzymes, accumulation and chemical forms of cadmium (Cd) in cucumber when exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of leaf, stem, root, fruit and plant, and concentrations and accumulation of Cd significantly differed between two varieties of cucumber Yanbai and Jinyou 1. With increasing levels of Se, the contents of MDA in the leaves of Yanbai increased, but the contents of MDA in the leaves of Jinyou 1 decreased. The contents of MDA in the roots of Yanbai first increased and then decreased, while the contents of MDA in Jinyou 1 first decreased and then increased. The variation trends of CAT, SOD and POD in the leaves and roots of both varieties were different with increasing levels of Se. The concentrations of different chemical forms of Cd in the fruit decreased after spraying of Se, compared with the control. Cadmium concentrations in the leaves, stem, roots and fruit of both varieties decreased by 3.2%-17.9%, 14.6%-28.2%, 5.1%-18.5% and 60.6%-75.8% in the presence of Se when exposed to Cd. Accumulation of Cd in the plant of both varieties was in order of Jinyou 1 > Yanbai in the presence or absence of Na2SeO3.

[Effect of Nano Zeolite on Chemical Fractions of Cd in Soil and Its Uptake by Cabbage].

Incubation experiments were carried out to investigate the influence of different nano zeolite (NZ) and ordinary zeolite (OZ) levels(0, 5, 10 and 20 g · kg⁻¹) on the change trends in fraction distribution coefficient (FDC) of Cd when exposed to different Cadmium (Cd) levels (1, 5, 10 and 15 mg · kg⁻¹), and pot experiments were carried out to investigate their influence on soil Cd fraction and Cd uptake by cabbage. The results in incubation experiments showed that the application of nano zeolite as well as ordinary zeolite effectively decreased the FDC of exchangeable Cd and increased the FDC of Fe-Mn oxide fraction. The FDC of soil Cd from 0 d to 28 d was deceased at first, then increased and tended to be stable, and finally increased. At the end of incubation, the FDC of soil exchangeable Cd decreased from 72.0%-88.0% to 30.0%-66.4%. Exchangeable fraction Cd was the most dominant Cd fraction in soil during the whole incubation. The results in pot experiment indicated that the application of nano zeolite and ordinary zeolite decreased the concentration and FDC of soil exchangeable Cd, and concurrently the concentration and FDC of Cd in carbonate, Fe-Mn oxide, organic matter and residual fraction were increased. The lowest EX-Cd was observed in the treatment with high dose of nano zeolite (20 g · kg⁻¹). The FDC of exchangeable Cd showed significant negative relationship with the soil pH (P < 0.05), and was concurrently extremely positively correlated with Cd concentration in shoot and root of cabbage (P < 0.01). Soil pH increased by 1.8%-45.5% and 6.1%-54.3% in the presence of zeolite when exposed to 5 mg · kg⁻¹ 1 and Cd, respectively; FDC of exchangeable Cd decreased by 16.3%-47.7% and 16.2%-46.7%; Cd concentration in each tissues of cabbage decreased by 1.0%-75.0% and 3.8%-53.2%, respectively. Moreover, the reduction effect of nano zeolite on soil and plant Cd was better than that of ordinary zeolite. The growth of cabbage was stimulated by low and medium zeolite doses (≤ 10 g · kg⁻¹), while inhibited by high zeolite doses (20 g · kg⁻¹). Compared to ordinary zeolite, the biomass of Chinese cabbage was significantly increased by Nano zeolite, while the exchangeable Cd in soil as well as Cd concentration and Cd accumulation of cabbage were significantly reduced.

[Effect of Ryegrass and Arbuscular Mycorrhizal on Cd Absorption by Varieties of Tomatoes and Cadmium Forms in Soil].

Field trial was carried out to investigate the effects of ryegrass and arbuscular mycorrhizal single or compound treatment to two varieties of tomato ("Defu mm-8" and "Luobeiqi") on the plant growth, concentrations and accumulations of Cd as well as the impact on microorganisms, enzyme activities, pH and Cd forms in soil when exposed to Cd (5.943 mg · kg⁻¹). The results showed that dry weights of fruit, root, stem, leaf and plant significantly increased by single or compound treatment of ryegrass and arbuscular mycorrhizal by 14.1%-38.4% and 4.2%-18.3%, 20.9%-31.5% and 8.4%-10.3%, 13.0%-16.8% and 3.0%-9.5%, 10.7%- 16.8% and 2.7%-7.6%, 14.3%-36.6% and 4.5%-16.8%, respectively. The amounts of bacteria, fungi, actinomycetes of soil and the activities of urease, invertase, acid phosphatase, catalase in soil were increased by single or compound treatment of ryegrass and arbuscular mycorrhizal, and the soil microorganism amounts and enzyme activities significantly differed between the two varieties of tomato and treatments (P < 0.05). Soil pH was increased by single or compound treatment of ryegrass and arbuscular mycorrhizal, while the concentrations of EXC-Cd, CAB-Cd, Fe-Mn-Cd and total Cd in soil were decreased, and the total Cd content was decreased by 16.9%-27.8%. Cadmium concentrations in fruit, leaf, stem and root of both varieties were significantly decreased by 6.9%-40.9%, 5.7%-40.1%, 4.6%-34.7% and 9.8%-42.4%, respectively. Cadmium accumulations in tomato were in order of leaf > stem > root > fruit. Comparing the two tomato varieties, Cd concentrations and Cd accumulations in fruit and plant were in order of "Luobeiqi" < "Defu mm-8" in the presence or absence of single or compound treatment of ryegrass and arbuscular mycorrhizal.

[Effects of ryegrass and arbuscular mycorrhiza on activities of antioxidant enzymes, accumulation and chemical forms of cadmium in different varieties of tomato].

Pot experiments were carried out to investigate the effects of ryegrass and arbuscular mycorrhiza on the plant growth, malondialdehyde (MDA), antioxidant enzyme activities of leaf and root, accumulation and chemical forms of cadmium (Cd) in tow varieties of tomato when exposed to Cd (20 mg x kg(-1)). The results showed that dry weights of fruit and plant, and contents of malondialdehyde (MDA) and antioxidant enzyme activities of leaf and root, and concentrations and accumulations of Cd significantly differed between two varieties of tomato. Dry weights of fruit, roots, stem, leaf and plant were increased by single or combined remediation of ryegrass and arbuscular mycorrhiza, while MDA contents and antioxidant enzyme activities of leaf and root reduced. The total extractable Cd, F(E), F(W), F(NaCl), F(HAc), F(HCl), and F(R) in fruit of two varieties of tomato reduced by 19.4% - 52.4%, 31.0% - 75.2%, 19.7% - 59.1%, 3.1% - 48.2%, 20.0% - 65.0%, 40.7% - 100.0% and 15.2% - 50.0%, respectively. Cadmium accumulations in tomato were in the order of leaf > stem > fruit > root. Cadmium concentrations in leaf, stem, root and fruit of both varieties decreased by single or combined remediation of ryegrass and arbuscular mycorrhiza, and Cd accumulations of stem and plant of two varieties also reduced. Cd accumulations in fruit of two varieties decreased by 42.9% and 43.7% in the combined remediation treatments, respectively. Tolerance and resistance of 'LUO BEI QI' on Cd was more than 'De Fu mm-8', and Cd concentrations and Cd accumulations in fruit and plant were in the order of 'LUO BEI QI' < 'De Fu mm-8' in the presence or absence of single or combined remediation of ryegrass and arbuscular mycorrhiza.

TMEDA-assisted effective direct ortho arylation of electron-deficient N-heteroarenes with aromatic Grignard reagents.

In the addition of TMEDA in toluene, aryl Grignards could effectively and site-specifically ortho-arylate electron-deficient heteroarenes under mild conditions. This endeavor successfully changed the old low-yielding reaction, aryl Grignard addition to N-heteroarenes, into an efficient procedure for heterobiaryls. The combination of the inexpensive aryl Grignards, TMEDA, the cost-free air, no use of any transition-metal catalyst, the mild reaction conditions, and the high-yielding gram-scale results enables this new procedure to be cost-effective and potentially utilizable in industry.