Multiple Conformations of Phosphodiesterase-5: IMPLICATIONS FOR ENZYME FUNCTION AND DRUG DEVELOPMENT

Phosphodiesterase-5 (PDE5) is the target for sildenafil, vardenafil, and tadalafil, which are drugs for treatment of erectile dysfunction and pulmonary hypertension. We report here the crystal structures of a fully active catalytic domain of unliganded PDE5A1 and its complexes with sildenafil or icarisid II. These structures together with the PDE5A1-isobutyl-1-methylxanthine complex show that the H-loop ( residues 660-683) at the active site of PDE5A1 has four different conformations and migrates 7-35 angstrom upon inhibitor binding. In addition, the conformation of sildenafil reported herein differs significantly from those in the previous structures of chimerically hybridized or almost inactive PDE5. Mutagenesis and kinetic analyses confirm that the H-loop is particularly important for substrate recognition and that invariant Gly(659), which immediately precedes the H-loop, is critical for optimal substrate affinity and catalytic activity

USP21 negatively regulates antiviral response by acting as a RIG-I deubiquitinase

Lys63-linked polyubiquitination of RIG-I is essential in antiviral immune defense, yet the molecular mechanism that negatively regulates this critical step is poorly understood. Here, we report that USP21 acts as a novel negative regulator in antiviral responses through its ability to bind to and deubiquitinate RIG-I. Overexpression of USP21 inhibited RNA virus–induced RIG-I polyubiquitination and RIG-I–mediated interferon (IFN) signaling, whereas deletion of USP21 resulted in elevated RIG-I polyubiquitination, IRF3 phosphorylation, IFN-α/β production, and antiviral responses in MEFs in response to RNA virus infection. USP21 also restricted antiviral responses in peritoneal macrophages (PMs) and bone marrow–derived dendritic cells (BMDCs). USP21-deficient mice spontaneously developed splenomegaly and were more resistant to VSV infection with elevated production of IFNs. Chimeric mice with USP21-deficient hematopoietic cells developed virus-induced splenomegaly and were more resistant to VSV infection. Functional comparison of three deubiquitinases (USP21, A20, and CYLD) demonstrated that USP21 acts as a bona fide RIG-I deubiquitinase to down-regulate antiviral response independent of the A20 ubiquitin-editing complex. Our studies identify a previously unrecognized role for USP21 in the negative regulation of antiviral response through deubiquitinating RIG-I

The Policy of Ecological Forest Rangers (EFRs) for the Poor: Goal Positioning and Realistic Choices—Evidence from the Re-Employment Behavior of EFRs in Sichuan, China

Ecological or environmental compensation policies are usually designed with multiple policy objectives such as protecting the ecological environment and promoting farmers’ livelihoods, but in the enforcement process, there are often inconsistencies between realistic choices and policy objectives. Based on pooled cross-section data from the 2017–2019 public announcement of the selection of ecological forest rangers (EFRs, who mainly refers to manage and protect forests, grasslands, deserts and rivers, and report or prevent the situation or behavior of the forest area disasters, animal and plant resources, and infrastructure damage in time) among the poor in Sichuan Province in China, we used the Probit model to analyze the influencing factors of the re-employment behavior of EFRs among the poor, with the aim of assessing the differences between central government goal positioning and local government enforcement options. We find that (1) EFRs from poor households who have not yet escaped poverty and have a high per capita income level are given priority to be re-employed. This finding shows that the policy of ecological forest rangers for the poor (PEFRP, it mainly refers to an environmental protection policy that only hires the poor) pays close attention to poverty reduction goals, but it does not consider the poorest people because the EFRs with a higher income obtain higher re-employment opportunities. (2) Age, health, and education, which represent the human capital level, have no significant impact on renewal. This finding shows that the local government has not jointly achieved the goal of “poverty reduction and environmental protection” in the enforcement of the PEFRP and has deviated from the initial goal positioning of the central government. Therefore, in order to achieve the multiple policy objectives such as poverty reduction and environmental protection together, future policy enforcement needs to be adjusted in terms of local administrative assessment and the selection and recruitment of EFRs

Comprehensive Experimental Study of Affecting Factors on Rectangular Roadway Stability

In this paper, two methods of orthogonal numerical simulation test and similar material simulation test are used to study the influence of five factors on the stability of rectangular roadway: roadway width, roadway height, roadway buried depth, lateral pressure coefficient of surrounding rock, and comprehensive strength of surrounding rock. The results show that five factors have influence on the stability of roadway, but the degree of influence is different. The depth of the tunnel and the coefficient of the side pressure of the surrounding rock are positively correlated with the stability of the tunnel; the comprehensive strength of the surrounding rock is negatively correlated with the stability of the tunnel, but the correlation between the width and height of the tunnel and the stability of the tunnel is not obvious. The results of orthogonal numerical simulation test and similar material simulation test verify each other. The results of the field practice of the Fucun coal mine are basically consistent with the results of the two test methods, which shows that the research results have a certain guiding effect on the field roadway support

The Impact of Rural Population Mobility on Fertility Intention under the Comprehensive Two-Child Policy: Evidence from Rural China

Declining fertility rates pose challenges to global economic, social, cultural and political development. Low fertility rates among rural floating populations are exacerbating these challenges. However, it is not clear whether and to what extent rural population mobility (RPM) has reduced migrants’ willingness to have children. At the same time, rural migration may represent a self-selection behavior (i.e., selection bias), and traditional measurement methods may be insufficient for effectively estimating the quantitative impacts of rural migration. Accordingly, the data from 1734 rural households from 28 provinces in mainland China were collected in the current study, and endogenous switching regression (ESR) models were used to correct the selection bias to quantitatively evaluate the impacts of RPM on fertility intention. The results revealed the following: (1) For rural residents who choose to move, if they chose not to move, their willingness to give birth would increase by 19.820%, their willingness to have female children would increase by 48.526%, and their willingness to have male children would drop by 26.711%. (2) For rural residents who choose not to move, if they chose to move, their willingness to give birth would drop by 55.982%, their willingness to have female children would drop by 18.294%, and their willingness to have male children would drop by 55.106%. (3) For eastern rural residents who choose to move, if they chose not to move, their willingness to give birth would decrease by 40.273%. For midwestern rural residents who choose to move, if they chose not to move, their willingness to give birth would increase by 24.786%. (4) For eastern rural residents who choose not to move, if they chose to move, their willingness to give birth would increase by 11.032%. (5) For midwestern rural residents who choose not to move, if they chose to move, their willingness to give birth would drop by 71.744%. The abovementioned findings can provide research support for other low-fertility countries or regions toward increasing fertility rates and addressing any imbalances in current gender ratios. They can also help to provide realistic strategies for alleviating the global population crisis

Feminization of Agriculture: Do Female Farmers Have Higher Expectations for the Value of Their Farmland?—Empirical Evidence from China

An individual’s expectations for the value of farmland are a manifestation of his or her awareness of farmland rights and interests. Differences between male and female farmers in their use of farmland, employment, education, and rights protection may ultimately lead to differences in the evaluation of land value between the two groups. Clarifying such gender differences in the valuation of farmland and the reasons for them is of great significance for the formulation of policies and scientific research in areas such as the protection of rural women’s rights, nonagricultural employment, and land transfer. In the context of the global “feminization of agriculture”, we start with individuals’ psychological expectations for the value of farmland. We use data on farmland from the 2015 China Household Finance Survey (CHFS) and estimate an OLS regression model. The moderating effects model identifies the impact of gender differences on such expectations and the underlying mechanism. We find that (1) rural female farmers’ psychological expectations for the value of farmland are much lower than those of males due to their disadvantages in receiving information through policy publicization and their greater willingness to transfer into nonagricultural employment, and (2), according to the heterogeneity analysis, better educated female farmers and those living in areas with greater economic and social development expect farmland to be more valuable. These conclusions show that female farmers are currently less aware of their economic rights in rural China than male farmers, and that education, policy propaganda, and economic and social underdevelopment hinder their awareness of women’s rights. We propose policy suggestions to ensure women’s educational rights, promote the adjustment of the industrial structure and of policy propaganda, and balance regional economic and social development

Does the Policy of Ecological Forest Rangers (EFRs) for the Impoverished Populations Reduce Forest Disasters?—Empirical Evidence from China

The effective prevention and control of forest disasters is important for forest resources and the well-being of those living in forested areas. This study evaluates the impact of a policy that employs a rural impoverished population as ecological forest rangers (EFRs) for the incidence of forest disasters. We estimate a generalized difference in differences (DID) model using nationwide provincial-level forest disaster data combined with regional data in all policy pilot areas. There are three primary findings. (1) The implementation of the EFR policy failed to effectively reduce the incidence of forest fires, forest pests, forest diseases, forest rodents and other forest disasters, which shows that the EFR policy has not achieved the goal of “forest protection”. (2) The effect of the EFR policy on forest disaster control is not significantly different among provinces with different forest resource endowments and different levels of social and economic development. This shows that there is no significant difference in the implementation of EFR policies between different forest resource endowments and different socioeconomic development areas. (3) The EFR policy failed to achieve the effective coordination of the dual goals of “poverty reduction” and “ecological protection”; this is the main reason for the failure to reduce the incidence of forest disasters while reducing poverty. The pressure of this policy neglected the “forest management and protection” function of the policy and the corresponding assessment requirements. At the same time, the central government also neglected the assessment of the prevention and control of “forest disasters” by local governments when implementing this policy. Ultimately, the opportunism of local governments and ecological rangers was strengthened. Therefore, the goals of environmental service payment items and the corresponding evaluation index settings need to be matched to truly achieve the established goals

Feminization of Agriculture: Do Female Farmers Have Higher Expectations for the Value of Their Farmland?—Empirical Evidence from China

An individual’s expectations for the value of farmland are a manifestation of his or her awareness of farmland rights and interests. Differences between male and female farmers in their use of farmland, employment, education, and rights protection may ultimately lead to differences in the evaluation of land value between the two groups. Clarifying such gender differences in the valuation of farmland and the reasons for them is of great significance for the formulation of policies and scientific research in areas such as the protection of rural women’s rights, nonagricultural employment, and land transfer. In the context of the global “feminization of agriculture”, we start with individuals’ psychological expectations for the value of farmland. We use data on farmland from the 2015 China Household Finance Survey (CHFS) and estimate an OLS regression model. The moderating effects model identifies the impact of gender differences on such expectations and the underlying mechanism. We find that (1) rural female farmers’ psychological expectations for the value of farmland are much lower than those of males due to their disadvantages in receiving information through policy publicization and their greater willingness to transfer into nonagricultural employment, and (2), according to the heterogeneity analysis, better educated female farmers and those living in areas with greater economic and social development expect farmland to be more valuable. These conclusions show that female farmers are currently less aware of their economic rights in rural China than male farmers, and that education, policy propaganda, and economic and social underdevelopment hinder their awareness of women’s rights. We propose policy suggestions to ensure women’s educational rights, promote the adjustment of the industrial structure and of policy propaganda, and balance regional economic and social development

Will the Experience of Human–Wildlife Conflict Affect Farmers’ Cultivated Land Use Behaviour? Evidence from China

Effectively managing and mitigating “human–wildlife conflict” (HWC) by adjusting the use of cultivated land to realise the coexistence of humans and wildlife plays an important role in protecting biodiversity, ensuring food security, improving cultivated land use efficiency, and improving the livelihoods of community residents in nature reserves. Based on the “harmful experience–expectation change–behavioural adjustment” theoretical analysis framework and survey data on 1008 farmers in China’s Giant Panda National Park, this paper uses a binary logit model and a mediating utility model to analyse the effect of HWC experience on the cultivated land use of farmers and the action mechanisms. The results show the following: (1) HWC experience increases the probability that farmers’ cultivated land use behaviour will be adjusted, which will not only increase the probability that farmers’ planting structure of cultivated land will be adjusted but also increase the probability that farmers will abandon cultivated land. (2) Farmers in the national park have a higher probability of adjusting their cultivated land use behaviour after experiencing HWCs than those outside the national park. Farmers in the national park mainly prefer to adjust the planting structure, while farmers outside the park are more inclined to abandon cultivated land. (3) Low-income farmers are more likely to adjust their cultivated land use behaviour after experiencing HWCs than high-income farmers. The low-income group mainly tends to adjust the planting structure of cultivated land, while the high-income group is more inclined to directly abandon cultivated land. (4) The farmers in the group with a high degree of dependence on cultivated land for their livelihood have a higher probability of adjusting their cultivated land use behaviour after experiencing HWC than those in the low-dependency group, and they tend to adjust the planting structure. (5) HWC experience mainly improves farmers’ adjustment of cultivated land use behaviour by improving their awareness of future risks of HWC. In other words, “HWC” will change the behavioural decision-making of farmers and the differences in constraints, such as different regions and different income levels, will lead to differences in “HWC” affecting farmers’ behaviours. The conclusions of this paper not only help in understanding the adjustment mechanism of farmers’ cultivated land use behaviour in the context of HWCs but also provide a decision-making reference for actively changing cultivated land use methods to address HWCs

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS