China's strictest water policy: Reversing water use trends and alleviating water stress.

Growing water problems have promoted the Chinese government to implement the strictest water resources management system (SWRMS), the first national policy that puts into practice the concept of "safe operating space" for human water use. Here, we investigate the impact of the SWRMS on China's water use and water stress based on a newly compiled high-resolution and multi-sectoral water use dataset. Results indicate that China's total water use (TWU) increased significantly from 549 km3 yr-1 to 610 km3 yr-1 between 2000 and 2012 (i.e., the pre-SWRMS period), but decreased remarkably in the post-SWRMS period (2012-2020), reaching 565 km3 yr-1 by the year 2020. The decline in TWU was attributed to the improvements of irrigation and industrial water use efficiency (WUE), which were strictly controlled by the SWRMS at various administrative levels of China. The improved WUE has yielded about ∼90 km3 of water savings per year, freeing 17 prefectures from extreme water stress that affects 6% of China's population and 10% of its GDP. Although the improved WUE caused a significant decrease in TWU, the reduction in China's average water stress was insignificant due to the considerable influence of water availability. We further identified hotspots with great potential for water stress reduction, mainly in northwestern China, and hotspots at high risks of water security, primarily on the North China Plain. This study underscores the crucial role of the SWRMS in addressing China's water shortage and provides valuable insights to other countries grappling with water problems in defining their own "safe water operating spaces".

A Versatile Assembly Approach toward Multifunctional Supramolecular Poly(Ionic Liquid) Nanoporous Membranes in Water.

Hydrogen (H)-bonding-integration of multiple ingredients into supramolecular polyelectrolyte nanoporous membranes in water, thereby achieving tailor-made porous architectures, properties, and functionalities, remains one of the foremost challenges in materials chemistry due to the significantly opposing action of water molecules against H-bonding. Herein, a strategy is described that allows direct fusing of the functional attributes of small additives into water-involved hydrogen bonding assembled supramolecular poly(ionic liquid) (PIL) nanoporous membranes (SPILMs) under ambient conditions. It discloses that the pore size distributions and mechanical properties of SPILMs are rationally controlled by tuning the H-bonding interactions between small additives and homo-PIL. It demonstrates that, benefiting from the synergy of multiple noncovalent interactions, small dye additives/homo-PIL solutions can be utilized as versatile inks for yielding colorful light emitting films with robust underwater adhesion strength, excellent stretchability, and flexibility on diverse substrates, including both hydrophilic and hydrophobic surfaces. This system provides a general platform for integrating the functional attributes of a diverse variety of additives into SPILMs to create multifunctional and programmable materials in water.

Large-Scale and Controllable Syntheses of Covalently-Crosslinked Poly(ionic liquid) Nanoporous Membranes.

Herein, we report an exciting synthetic procedure for the scalable and controllable fabrication of covalently crosslinked poly(ionic liquid) (PIL) nanoporous membranes (CPILMs) in water solution under ambient conditions. We found that the pore sizes, flexibility and compositions of freestanding CPILMs can be finely tailored by a rational structural choice of PIL, diketone and aldehyde. Studies on the CPILM formation mechanism revealed that hydrogen bonding-induced phase separation of amino-functionalized homo-PIL between its polar and apolar domains coupled with structural rearrangements due to the Debus Radsizewski reaction-triggered ambient covalent crosslinking process created a stable three-dimensionally interconnected pore system in water solution. Employing structurally stable CPILMs in ion sieving devices resulted in an excellent Li+ /Mg2+ separation efficiency due to the positively charged nature and "Donann" effects. This green, facile yet versatile approach to the production of CPILMs is a conceptually distinct and commercially interesting strategy for making useful nanoporous functional polyelectrolyte membranes.

Jinfeng pills ameliorate premature ovarian insufficiency induced by cyclophosphamide in rats and correlate to modulating IL-17A/IL-6 axis and MEK/ERK signals.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfeng Pill (JFP) is a classical Chinese medicine formula and composed of 9 herbs, including Epimedium brevicornu Maxim (Yinyanghuo), Cervus elaphus Linnaeus (Lurong), Panax ginseng C.A.Mey. (Renshen), Equus asinus (EJiao), Ligustrum lucidum W.T.Aiton (Nvzhenzi), Reynoutria multiflora (Thunb.) Moldenke (Heshouwu), Curculigo orchioides Gaertn (Xianmao), Neolitsea cassia (L.) Kosterm. (Rougui) and Leonurus japonicus Houtt. (Yimucao). The formula is clinically used to regulate menstrual cycle and alleviate polycystic ovarian syndrome due to its capabilities of ovulation induction. It is therefore presumed that JFP could be used for the therapy of premature ovarian insufficiency (POI) but the assumed efficacy has not been fully substantiated in experiment. AIM OF STUDY: To evaluate the effectiveness of JFP on cyclophosphamide (CTX)-induced POI and preliminarily explore its potential mechanisms of action. MATERIAL AND METHODS: An experimental rat model of POI was established by using CTX induction to assess the efficacy of JFP. The potential targets of action for JFP alleviating POI were predicted by the combination of network pharmacology and transcriptomics and finally validating by RT-qPCR and Western blot. RESULTS: JFP alleviated the damages of ovarian tissue induced by CTX in the rat model of POI via significantly decreasing serum levels of FSH and LH and the ratio of FSH/LH and increasing the levels of E2 and AMH, accompanied with promoting ovarian folliculogenesis and follicle maturity and reversing the depletion of follicle pool. With the analysis of network pharmacology, pathways in cancer, proteoglycans in cancer, PI3K-AKT, TNF and FoxO signaling pathways were predicted to be influenced by JFP. The results of RNA-seq further revealed that IL-17 signaling pathway was the most important pathway regulated by both CTX and JFP, following by transcriptional misregulation in cancer and proteoglycans in cancer. Combining the two analytical methods, JFP likely targeted genes associated with immune regulation, including COX-2, HSP90AA1, FOS, MMP3 and MAPK11 and pathways, including IL-17,Th17 cell differentiation and TNF signaling pathway. Finally, JFP was validated to regulate the mRNA expression of FOS, FOSB, FOSL1, MMP3, MMP13 and COX-2 and decrease the release of IL-17A and the protein expression of IL-6 and suppress the phosphorylation of MEK1/2 and ERK1/2 in CTX induced POI rats. CONCLUSION: Jinfeng Pill is effective to ameliorate the symptoms of POI induced by CTX in the model of rats and its action is likely associated with suppressing IL-17A/IL-6 axis and the activity of MEK1/2-ERK1/2 signaling.

The Antiproliferative and Proapoptotic Effects of Cucurbitacin B on BPH-1 Cells via the p53/MDM2 Axis.

Cucurbitacin B (Cu B), a triterpenoid compound, has anti-inflammatory and antioxidant activities. Most studies only focus on the hepatoprotective activity of Cu B, and little effort has been geared toward exploring the effect of Cu B on the prostate. Our study identified that Cu B inhibited the proliferation of the benign prostatic hyperplasia epithelial cell line (BPH-1). At the molecular level, Cu B upregulated MDM2 and thrombospondin 1 (THBS1) mRNA levels. Immunocytochemistry results revealed that the protein expressions of p53 and MDM2 were upregulated in BPH-1 cells. Furthermore, Cu B upregulated THBS1 expression and downregulated COX-2 expression in the BPH-1 cell supernatant. Altogether, Cu B may inhibit prostate cell proliferation by activating the p53/MDM2 signaling cascade and downregulating the COX-2 expression.

Thyroid Hormone Receptor ß Knockdown Reduces Suppression of Progestins by Activating the mTOR Pathway in Endometrial Cancer Cells.

Progestin resistance is a major obstacle to conservative therapy in patients with endometrial cancer (EC) and endometrial atypical hyperplasia (EAH). However, the related inducing factor is yet unclear. In this study, thyroid hormone and its receptor α (TRα) and ß (TRß) of patients were assayed. THRB-silenced RL95-2 and KLE EC cells were cultured to investigate the response of progestins. Transcriptomics and Western blotting were performed to investigate the changes in signaling pathways. We found that THRB, rather than THRA, knockdown promoted the viability and motilities of RL95-2 cells but not KLE cells. The suppressive effect of progestins on cell growth and motility significantly decreased in THRB-silenced RL95-2 cells. Multiple proliferation-related signaling pathways were enriched, and the activities of mammalian targets of rapamycin (mTOR)/4e-binding protein 1 (4EBP1)/eukaryotic translation initiation factor 4G (eIF4G) rather than phosphorylated protein kinase B (Akt) were remarkably boosted. Progestin treatment enhanced the effects, and the augmentation was partially abated on supplementation with T3. In THRB-knockdown KLE cells, the progestins-activated partial signaling pathway expression (either mTOR or eIF4G), and supplementation with T3 did not induce noticeable alterations. The serum levels of triiodothyronine (T3) were significantly lower in patients with EC compared with healthy women. A strong expression of TRß was observed in most patients with EC and EAH sensitive to progestin treatment. In contrast, TRα positive expression was detected in less than half of the patients sensitive to progestin therapy. In conclusion, THRB knockdown enhanced the viability and motility of type I EC cells and attenuated the suppressive effects of progestins by activating the mTOR-4EBP1/eIF4G pathway. Lower expression of THRB is likely correlated with progesterone resistance.

Chinese-style incentives: The intraindustry ripple effects of CEO awards.

Considering the background of traditional Chinese culture, which emphasizes that "when we see outstanding people, we should think of emulating them", and social comparison theory, this study explores how CEO awards impact the R&D investment of award-winning CEOs' competitors. The results show that award-winning CEOs' competitors increase R&D investment in the postaward period relative to the preaward period. We further find that CEO awards' "gold content", the social attention of award-winning CEOs' competitors, the similarity between award-winning CEOs and their competitors, and industry competitive pressure are important factors affecting the size of ripple effects. Empirical evidence also shows that the intraindustry ripple effects of CEO awards significantly improve the firm performance and value of competitors. In a robustness test, we confirm CEO awards' intraindustry ripple effects from the perspective of the number of patent applications. The ripple effects of CEO awards are still valid after using PSM-DID to alleviate endogeneity problems and considering the right-side distribution of R&D investment.

nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors.

Anxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.