Small-size Ti3C2Tx MXene nanosheets coated with metal-polyphenol nanodots for enhanced cancer photothermal therapy and anti-inflammation.

As a controllable, simple method with few side effects, near-infrared (NIR) light-based photothermal therapy (PTT) has been proven an effective cancer therapeutic approach. However, PTT-induced inflammation is a potential negative factor. And the overexpressed heat shock proteins (HSPs) by cancer cells can protect them from hyperthermia during PTT. In this work, small-size Ti3C2Tx MXene nanosheets with high photothermal conversion efficiency in the region of NIR, high cargo loading capability and good free radical scavenging capability were chosen for cancer PTT and anti-inflammation. And (-)-epigallocatechin gallate (EGCG) was applied to form EGCG/Fe metal-polyphenol nanodots on the nanosheets. EGCG being released in acid cancer cells could reduce the expression of HSPs and could be used for anti-inflammation. As a result, the complex nanosheets named MXene@EGCG could achieve enhanced cancer PTT and be anti-inflammatory. Both in vitro and in vivo studies proved the good photothermal ability of MXene@EGCG and demonstrated that it could inhibit the expression of HSPs in tumor cells and relieve PTT-induced inflammation. Therefore, the nanosheets show good results in tumor ablation with a low level of inflammation, which provides another possibility for cancer therapy. STATEMENT OF SIGNIFICANCE: Photothermal therapy (PTT)-induced inflammation plays an essential role in some important stages of tumor development and is unfavorable for cancer treatment. And hyperthermia leads to the overexpression of heat shock proteins (HSPs) in cancer cells, which limits the therapeutic effect of PTT. Therefore, we coated small-size Ti3C2Tx MXene nanosheets with (-)-epigallocatechin gallate (EGCG)/Fe metal-polyphenol nanodots and named them as MXene@EGCG. This system shows a good photothermal conversion efficiency at 808 nm. And it can release EGCG in cancer cells to inhibit the expression of HSPs, thus achieving an enhanced cancer PTT. Both MXene and EGCG can also diminish the PTT-trigged inflammation. Both in vitro and in vivo studies prove the good anti-cancer PTT effect and anti-inflammation capability of MXene@EGCG.

Efficacy and Safety of Traditional Chinese Herbal Medicine for Antipsychotic-Related Constipation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Constipation is a common but often ignored side effect of antipsychotic treatment, although it is associated with adverse outcomes. The results of the efficacy and safety of traditional Chinese herbal medicine (TCM) in treating constipation are mixed across studies. This is a systematic review and meta-analysis of randomized controlled trials (RCTs) of the efficacy and safety of TCM compared to Western medicine (WM) in treating antipsychotic-related constipation. Methods: Major international electronic (PubMed, EMBASE, Cochrane Library, and Web of Science) and Chinese (Wanfang, WeiPu VIP, SinoMed, and CNKI) databases were searched from their inception to November 29, 2020. Meta-analysis was performed using the random-effects model. Results: Thirty RCTs with 52 arms covering 2,570 patients in the TCM group and 2,511 patients in the WM group were included. Compared with WM, TCM alone was superior regarding the moderate response rate [risk ratio (RR) = 1.165; 95% confidence interval (CI): 1.096-1.238; P < 0.001], marked response rate (RR = 1.437; 95% CI: 1.267-1.692; P < 0.001), and remission rate (RR = 1.376; 95% CI: 1.180-1.606; P < 0.001) for constipation, while it was significantly associated with lower risk of rash (RR = 0.081; 95% CI: 0.019-0.342; P = 0.001). For the moderate response rate, meta-regression analyses revealed that publication year (ß = -0.007, P = 0.0007) and Jadad score (ß = 0.067, P < 0.001) significantly moderated the results. For the remission rate, subgroup and meta-regression analyses revealed that the geographical region (P = 0.003), inpatient status (P = 0.035), and trial duration (ß = 0.009, P = 0.013) significantly moderated the results. Conclusions: The efficacy of TCM for antipsychotic-related constipation appeared to be greater compared to WM, while certain side effects of TCM, such as rash, were less frequent.

Changes of Ghrelin/GOAT axis and mTOR pathway in the hypothalamus after sleeve gastrectomy in obese type-2 diabetes rats.

AIM: To examine the changes of the ghrelin/ghrelin O-acyltransferase (GOAT) axis and the mammalian target of rapamycin (mTOR) pathway in the hypothalamus after sleeve gastrectomy. METHODS: A total of 30 obese type-2 diabetes Sprague-Dawley (SD) rats, 6 wk of age, fed with high-sugar and high-fat fodder for 2 mo plus intraperitoneal injection of streptozotocin were randomly divided into three groups: non-operation group (S0 group, n = 10), sham operation group (Sh group, n = 10) and sleeve gastrectomy group (SG group, n = 10). Data of body mass, food intake, oral glucose tolerance test (OGTT), acylated ghrelin (AG) and total ghrelin (TG) were collected and measured at the first day (when the rats were 6 wk old), preoperative day 3 and postoperative week 8. The mRNA expression of preproghrelin, GOAT and neuropeptide Y (NPY), and protein expression of ghrelin, GOAT, GHSR and the mTOR pathway (p-Akt, p-mTOR and p-S6) were measured in the hypothalamus. RESULTS: SG can significantly improve metabolic symptoms by reducing body mass and food intake. The obese rats showed lower serum TG levels and no change in AG, but the ratio of AG/TG was increased. When compared with the S0 and Sh groups, the SG group showed decreased TG (1482.03 ± 26.55, 1481.49 ± 23.30 and 1206.63 ± 52.02 ng/L, respectively, P < 0.05), but unchanged AG (153.06 ± 13.74, 155.37 ± 19.30 and 144.44 ± 16.689 ng/L, respectively, P > 0.05). As a result, the ratio of AG/TG further increased in the SG group (0.103 ± 0.009, 0.105 ± 0.013 and 0.12 ± 0.016, respectively, P < 0.05). When compared with the S0 group, SG suppressed mRNA and protein levels of preproghrelin (0.63 ± 0.12 vs 0.5 ± 0.11, P < 0.05) and GOAT (0.96 ± 0.09 vs 0.87 ± 0.08, P < 0.05), but did not change NPY mRNA expression (0.61 ± 0.04 vs 0.65 ± 0.07, P > 0.05) in the hypothalamus. The protein levels of p-Akt, p-mTOR and p-S6 were higher in the SG group, which indicated that the hypothalamic mTOR pathway was activated after SG at the postoperative week 8. CONCLUSION: The reduction of ghrelin expression and activation of the mTOR pathway might have opposite effects on food intake, as SG improves obesity and T2DM.

Adding perches for cross-pollination ensures the reproduction of a self-incompatible orchid.

BACKGROUND: Outcrossing is known to carry genetic advantages in comparison with inbreeding. In many cases, flowering plants develop a self-incompatibility mechanism, along with a floral component adaptation mechanism, to avoid self-pollination and to promote outbreeding. Orchids commonly have a lip in their flower that functions as the a visiting plate for insect pollinators. Aside from the lip, however, many species (including Coelogyne rigida) have sheaths around the axis of inflorescence. The function of these sheaths remains unknown, and has long been a puzzle to researchers. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the function of these sheaths in relation to the lip and the pollinators, as well as their role in the modes of pollination and reproduction of Coelogyne rigida in 30 flowering populations of orchids in the limestone area of Southeast Yunnan, China. We found that self-incompatible C. rigida developed specialized bird perches around the basal axis of inflorescence to attract sunbirds and to complement their behavioral tendency to change foraging locations frequently. This self-incompatibility mechanism operates separately from the floral component adaptation mechanism. This mechanism thus prevents bees from repeatedly visiting the floral lip of the same plant which, in turn, results in autogamy. In this way, instead of preventing autogamy, C. rigida responds to these negative effects through a highly efficient cross-pollination method that successfully transfers pollen to different plants. CONCLUSIONS: The proposed method ensures reproductive success, while offsetting the infertile self-pollination by insects, thereby reducing mating costs and addressing the lack of cross-pollination. The adaptation provides a novel and striking example of structural adaptation that promotes cross-pollination in angiosperms.