Digital economy exhibits varying degrees of mitigation of air pollution in China: Total cities-economic subdivisions-urban agglomerations.

Air pollution is a challenge for many cities. The digital economy enhances support for environmental pollution management, while the mechanisms and scaling heterogeneity remain unclear. This study explored the contribution of digital economy development to PM2.5 concentrations control in China and driving mechanisms in different economic subregions and urban agglomerations. Results show that the spillover transfer effect on air pollution mitigation far exceeded the direct effect at different scales. At the national scale, the air pollution mitigation effect of digital economy was mainly through empowering industrial structure optimization and green technology innovation, while it also affected economic subregions and urban agglomerations through varying scenario combinations of pathways with structural optimization, green production, resource allocation, and technology innovation. Research findings provide support for cross-regional joint management strategies of digital economy and air quality and designing regionally differentiated pollution control pathways in the digital economy dimension.

Dynamics of ecosystem services and nonlinear responses to increased anthropogenic pressure.

Escalating global human activities elicit diverse ecosystem service responses, yet understanding remains limited. This study establishes a framework to clarify these responses, focusing on the Yangtze River Economic Belt in China. Analyzing 2000-2020 data, it calculates ecosystem service economic value and human footprint index. It introduces the ecosystem services response index and comprehensive responsiveness index to assess response characteristics and intensity to anthropogenic pressures. Results show a fluctuating decline in ecosystem services and an increase in anthropogenic pressures. There is a nonlinear relationship: ecosystem services decline with rising pressures, following a U-shaped trend. Notably, nonurban agglomerations experience more significant ecosystem service evolution than urban agglomerations due to differing environmental conditions. This highlights regional disparities in human activity impacts on ecosystems, crucial for planning.

Design and simulation of a cross-regional collaborative recycling system for secondary resources: A case of lead-acid batteries.

In emerging economies, a significant amount of secondary resources are recycled by the informal sector, which can seriously harm the environment. However, some previous studies of industry management policy design ignored geographical factors. This paper introduces Geographic Information Systems into an agent-based cross-regional recycling model, and employs lead-acid batteries as an example. The model quantitatively displays the evolution of recycling markets in 31 provinces in Mainland China. Results show that: (1) High subsidies can significantly increase the number of formal enterprises in the short term, but their effectiveness decreases when the proportion of government funds in subsidies is above 80% in the long run; (2) The number of illegal recycling enterprises increases by 294% in eight inland provinces (e.g., Ningxia, Xinjiang) when all funds are invested in supervision, but this number is quite small in subsidy policy scenarios; (3) In four eastern regions, including Beijing and Tianjin, the number of illegal recycling enterprises decreases by 84% if supervision is more favored than subsidy; (4) In the optimal case where spatiotemporal factors are considered in all 31 regions, illegal recycling enterprises and waste lead emissions can be reduced by 95.59% and 45.85% nationwide. Our proposed recycling model offers a detailed simulation of multiple regions and diverse stakeholders, and serves as a useful reference for targeted recovery policies. Governments in inland regions like Ningxia and Xinjiang should implement subsidy policies, while supervision policies should be implemented in developed regions like Beijing and Tianjin.

How does digital trade promote and reallocate the export technology complexity of the manufacturing industry? Evidence from 30 Chinese provinces, 2011-2020.

It is important for China to break the "low-end lock" of the manufacturing value chain worldwide by revealing how digital trade promotes and reallocates the export technology complexity of the manufacturing industry. Panel data for 30 provinces in China from 2011 to 2020 were employed to measure the digital trade development and export technology complexity of the manufacturing industry. Benchmark regression, intermediary effect regression, panel threshold and other models were used to test the promotion and reallocation of digital trade on the export technology complexity of the manufacturing industry. The findings are as follows: (1) Digital trade promotes the export technology complexity of the manufacturing industry, with significant regional heterogeneity (eastern, central and western regions), and the most obvious promotion in technology-intensive manufacturing. (2) Technological innovation and human capital play a reallocation role in the process of digital trade, affecting the technological complexity of manufacturing exports, with mediating effects of 14.19% and 8.61%, respectively. (3) Digital trade promotes and reallocates the export technology complexity of the manufacturing industry through industrial structure upgrading, and a nonlinear relationship was found. These results provide empirical support and a decision-making basis for digital trade in promoting the export technology complexity of the manufacturing industry. The development of digital trade should be encouraged; the differential development of digital trade in the eastern, central, and western regions should be boosted; importance should be attached to the intermediary incentive role of technological innovation and human capital; and the upgrading of the industrial structure should be promoted scientifically.

Nonlinear effects of socio-economic factors on urban haze in China: Evidence from spatial econometric smooth transition autoregressive regression approach.

In recent years, China has achieved numerous economic miracles but it has also been plagued by severe air pollution. The frequent hazy weather has severely restricted China's sustainable development. To investigate the nonlinear threshold effect of socio-economic factors on urban haze in China, this study constructs a spatial econometric Smooth Transition Autoregressive Regression (STAR) model based on the STIRPAT theory by using the remote sensing inversion PM2.5 data of 223 prefecture-level and above cities in China mainland during 2004-2016. In this study, the ARAR-STAR model is estimated by quasi-maximum likelihood estimation, and the accuracy of parameter estimation is verified by Monte Carlo simulation, which proves that the ARAR-STAR model constructed in this study is robust. It is concluded that: there is a complex spatial nonlinear relationship between socio-economic factors such as economic development level, population density, advanced industrial structure, energy consumption, opening-up, and haze pollution. The effect of socio-economic factors on haze emission reduction under the spatial influence has complex heterogeneity with the smooth transition between high and low regimes with economic development. The ARAR-STAR model constructed in this paper, which has both individual fixed effects and time fixed effects, expands the form of existing spatial panel nonlinear models and enriches and implements the application of spatial panel smooth transfer threshold models in the environmental field. Not only can it provide policy recommendations for China to achieve "coordinated efficiency in pollution reduction and carbon reduction" as soon as possible, but it also contributes to China's plan to address global climate change and promote global sustainable development.

Activating Inducible T-cell Costimulator Yields Antitumor Activity Alone and in Combination with Anti-PD-1 Checkpoint Blockade.

In recent years, there has been considerable interest in mAb-based induction of costimulatory receptor signaling as an approach to combat cancer. However, promising nonclinical data have yet to translate to a meaningful clinical benefit. Inducible T-cell costimulator (ICOS) is a costimulatory receptor important for immune responses. Using a novel clinical-stage anti-ICOS immunoglobulin G4 mAb (feladilimab), which induces but does not deplete ICOS+ T cells and their rodent analogs, we provide an end-to-end evaluation of the antitumor potential of antibody-mediated ICOS costimulation alone and in combination with programmed cell death protein 1 (PD-1) blockade. We demonstrate, consistently, that ICOS is expressed in a range of cancers, and its induction can stimulate growth of antitumor reactive T cells. Furthermore, feladilimab, alone and with a PD-1 inhibitor, induced antitumor activity in mouse and humanized tumor models. In addition to nonclinical evaluation, we present three patient case studies from a first-time-in-human, phase I, open-label, dose-escalation and dose-expansion clinical trial (INDUCE-1; ClinicalTrials.gov: NCT02723955), evaluating feladilimab alone and in combination with pembrolizumab in patients with advanced solid tumors. Preliminary data showing clinical benefit in patients with cancer treated with feladilimab alone or in combination with pembrolizumab was reported previously; with example cases described here. Additional work is needed to further validate the translation to the clinic, which includes identifying select patient populations that will benefit from this therapeutic approach, and randomized data with survival endpoints to illustrate its potential, similar to that shown with CTLA-4 and PD-1 blocking antibodies. Significance: Stimulation of the T-cell activation marker ICOS with the anti-ICOS agonist mAb feladilimab, alone and in combination with PD-1 inhibition, induces antitumor activity across nonclinical models as well as select patients with advanced solid tumors.

Research on the impact and mechanism of financial development on new urbanization: A case study of the Yangtze River Economic Belt.

Based on panel data of 108 cities in China's Yangtze River Economic Belt from 2003 to 2019, a multiple mediation model is used in this study to assess the impact and mechanism of financial development on new urbanization. The main conclusions are that financial development can directly promote the improvement of new urbanization and indirectly improve the level of new urbanization by increasing infrastructure investment, optimizing industrial structure, and enhancing human capital. Further, the financial development of middle-upstream cities has a stronger promoting effect on new urbanization. Whereas the financial development of downstream cities mainly promotes the construction of new urbanization through both infrastructure investment and industrial structure optimization, middle-upstream cities rely more solely on infrastructure investment.

The impact of transportation accessibility on industrial investment in the urban agglomeration around Poyang Lake in China-based on the perspective of ecological security constraints.

Based on the perspective of ecological security constraints, this research takes panel data of 42 counties (cities) in the urban agglomeration around Poyang Lake in China from 2000 to 2020 and uses a spatial econometric model to investigate the impact of transportation accessibility on industrial investment. The findings herein present an obvious spatial relationship between industrial investment among cities under ecological security constraints and reveal how transportation accessibility has a significant spatial effect on industrial investment in this area. Transportation accessibility has promoted industrial investment in the local region but restrained industrial investment in the surrounding areas. A series of endogenous and robustness tests strengthen this conclusion. Lastly, the effect of transportation accessibility on industrial investment in the UAAPYL is influenced by the lake's circle structure and shows obvious heterogeneity.

Loss of function of CMPK2 causes mitochondria deficiency and brain calcification.

Brain calcification is a critical aging-associated pathology and can cause multifaceted neurological symptoms. Cerebral phosphate homeostasis dysregulation, blood-brain barrier defects, and immune dysregulation have been implicated as major pathological processes in familial brain calcification (FBC). Here, we analyzed two brain calcification families and identified calcification co-segregated biallelic variants in the CMPK2 gene that disrupt mitochondrial functions. Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) isolated from these patients showed impaired mitochondria-associated metabolism pathways. In situ hybridization and single-cell RNA sequencing revealed robust Cmpk2 expression in neurons and vascular endothelial cells (vECs), two cell types with high energy expenditure in the brain. The neurons in Cmpk2-knockout (KO) mice have fewer mitochondrial DNA copies, down-regulated mitochondrial proteins, reduced ATP production, and elevated intracellular inorganic phosphate (Pi) level, recapitulating the mitochondrial dysfunction observed in the PBMCs isolated from the FBC patients. Morphologically, the cristae architecture of the Cmpk2-KO murine neurons was also impaired. Notably, calcification developed in a progressive manner in the homozygous Cmpk2-KO mice thalamus region as well as in the Cmpk2-knock-in mice bearing the patient mutation, thus phenocopying the calcification pathology observed in the patients. Together, our study identifies biallelic variants of CMPK2 as novel genetic factors for FBC; and demonstrates how CMPK2 deficiency alters mitochondrial structures and functions, thereby highlighting the mitochondria dysregulation as a critical pathogenic mechanism underlying brain calcification.

An infinite life cycle assessment model to re-evaluate resource efficiency and environmental impacts of circular economy systems.

Challenges exist in life cycle assessment (LCA) to evaluate resource efficiency and environmental impacts of circular economy systems. Rules attributing recycling benefits/burdens are inconsistent, causing system boundary ambiguity. Besides, LCAs covering one or several life cycles fail to capture the complete resource path, which leads to unfair assessment results for the primary life cycle. This paper develops an infinite life cycle assessment model, which integrates LCA, substance flow analysis, and a state transition matrix into an infinite-life-cycle framework. On this basis, algorithms are formulated to quantify the resource efficiency and attribute environmental impacts following the principle of whole first, then allocation. Our model is demonstrated by a case study of lead-acid batteries. Results show that the resource efficiency of lead in the infinite life cycle assessment model is at least 118.75% higher than that of primary lead derived from the typical finite life cycle models. Measured by the index of environmental toxicity potential, environmental impacts are transferred from the primary product life cycle to recycled product life cycles, with the range fluctuating from 66.26% to 68.12%. Our model enables scholars to make more reasonable assessments for circular economy systems based on traditional LCA adjustment. From the infinite-life-cycle perspective, sustainable production policies should focus on increasing the recycling rate of waste products rather than limiting the exploitation of natural resources.

Chinese environmentally extended input-output database for 2017 and 2018.

Environmental footprint analyses for China have gained sustained attention in the literature, which rely on quality EEIO databases based on benchmark input-output (IO) tables. The Chinese environmentally extended input-output (CEEIO) database series provide publically available EEIO databases for China for 1992, 1997, 2002, 2007, and 2012 with consistent and transparent data sources and database structure. Based on the latest benchmark IO tables for China for 2017 and 2018, here we develop the corresponding 2017 and 2018 CEEIO databases following the same method used to develop previous CEEIO databases. The 2017 and 2018 CEEIO databases cover 44 and 28 types of environmental pressures, respectively, and consider multiple sector classifications including ones consistent with previous CEEIO databases and ones following the 2017 China's national economy industry classification standard. A notable improvement in the 2017 and 2018 CEEIO databases is the comprehensive inclusion of CO2 emissions from additional industrial processes. This work provides a consistent update of the CEEIO database and enables a wide range of timely environmental footprint analyses related to China.

A human CD137×PD-L1 bispecific antibody promotes anti-tumor immunity via context-dependent T cell costimulation and checkpoint blockade.

Immune checkpoint inhibitors demonstrate clinical activity in many tumor types, however, only a fraction of patients benefit. Combining CD137 agonists with these inhibitors increases anti-tumor activity preclinically, but attempts to translate these observations to the clinic have been hampered by systemic toxicity. Here we describe a human CD137xPD-L1 bispecific antibody, MCLA-145, identified through functional screening of agonist- and immune checkpoint inhibitor arm combinations. MCLA-145 potently activates T cells at sub-nanomolar concentrations, even under suppressive conditions, and enhances T cell priming, differentiation and memory recall responses. In vivo, MCLA-145 anti-tumor activity is superior to immune checkpoint inhibitor comparators and linked to recruitment and intra-tumor expansion of CD8 + T cells. No graft-versus-host-disease is observed in contrast to other antibodies inhibiting the PD-1 and PD-L1 pathway. Non-human primates treated with 100 mg/kg/week of MCLA-145 show no adverse effects. The conditional activation of CD137 signaling by MCLA-145, triggered by neighboring cells expressing >5000 copies of PD-L1, may provide both safety and potency advantages.

Serine-ubiquitination regulates Golgi morphology and the secretory pathway upon Legionella infection.

SidE family of Legionella effectors catalyze non-canonical phosphoribosyl-linked ubiquitination (PR-ubiquitination) of host proteins during bacterial infection. SdeA localizes predominantly to ER and partially to the Golgi apparatus, and mediates serine ubiquitination of multiple ER and Golgi proteins. Here we show that SdeA causes disruption of Golgi integrity due to its ubiquitin ligase activity. The Golgi linking proteins GRASP55 and GRASP65 are PR-ubiquitinated on multiple serine residues, thus preventing their ability to cluster and form oligomeric structures. In addition, we found that the functional consequence of Golgi disruption is not linked to the recruitment of Golgi membranes to the growing Legionella-containing vacuoles. Instead, it affects the host secretory pathway. Taken together, our study sheds light on the Golgi manipulation strategy by which Legionella hijacks the secretory pathway and promotes bacterial infection.

Design and simulation of a secondary resource recycling system: A case study of lead-acid batteries.

The recycling of secondary resources is complicated as consumers, recyclers and governments are all involved in this process. In developing countries, compared to legal recyclers, illegal recyclers not only have cost advantages but also create serious pollution. Inappropriate management policies may cause disorder in the recycling market or inefficient fiscal management. This paper takes China's lead-acid batteries (LABs) from 2000 to 2015 as an example to construct a model of a secondary resource recovery system based on heterogeneous groups and analyzes the environmental and economic impacts of used LAB recycling. By simulating the implementation of different tax cuts, subsidies and regulatory policies by the government in each year, we observe the overall environmental impact of the recycling industry. This study finds that when the total amount of government expenditures is limited, the optimal policy combination emphasizes tax reduction and subsidy policies during the growth period of the recycling industry and uses more funds for supervision in the mature period. Under the balance of fiscal revenues and expenditures, the optimal policy combination can reduce the number of illegal recycling companies and waste lead emissions from the recycling market by 97.9% and 45.8%, respectively. Compared to research conducted using mathematical models and system dynamics models, this result is more in line with the actual situation, and the content is more intuitive. The government needs to adopt different policy combinations in different periods according to the state of the recycling market so that the recycling of secondary resources can achieve the optimal effect.

Effect of phosphorus and potassium addition on greenhouse gas emissions and nutrient utilization of a rice-fish co-culture system.

Greenhouse gas (GHG) emissions from aquaculture have gained widespread attention. However, the effect of phosphorus (P) and potassium (K) on GHG emissions from aquaculture systems has rarely been studied. In this study, we conducted a laboratory-scale experiment to investigate the effect of P and K addition on CH4 and N2O emissions and nutrient use efficiency in a rice-fish co-culture system. The results showed that the CH4 flux rate did not differ between the rice-fish co-culture (RF) and fish monoculture (F) systems. Phosphorus addition did not affect CH4 emission from the RF. In contrast, K addition significantly increased the CH4 emission from the RF by 148.4%. Dual P and K addition greatly increased the CH4 emission from the RF by six times, indicating an interactive effect of P and K on the stimulation of CH4 emission. Phosphorus addition strengthened the restorative effect of the RF on N2O emission, while K addition weakened the restorative effect of the RF on N2O emission. The combination of P and K did not affect the N2O emission from the RF. The application of P and K strengthened the restorative effect of rice on nitrogen (N) pollution in aquaculture water. Phosphorus and K addition significantly increased the rice biomass and nutrient in the harvested rice, but did not affect the fish biomass and nutrient in the harvested fish. Dual P and K addition increased the nutrient use efficiency in the rice-fish system. These results provide a reference for adjusting nutrient management to reduce GHG emissions and improve nutrient use efficiency in the rice-fish system.

Does technology advancement reduce aggregate carbon dioxide emissions? Evidence from 66 countries with panel threshold regression model.

The influence of technology advancement on carbon dioxide (CO2) emissions is complex and controversial, yet existing literature ignores the level of economic development in regard to its influential effect. With the panel threshold regression model, this research investigates the marginal and non-linear impacts of technology advancement on CO2 emissions along with the changes of economic development and presents the heterogeneity between different countries. The results are as follows: First, technology advancement and CO2 emissions have a non-linear inverted U-shaped relationship, which is significantly affected by different levels of economic development. When economic development exceeds a certain threshold, the impact turns from positive to negative. Second, the impact varies remarkably among different countries. We provide evidence for inverted U-shaped and N-shaped correlations in the Organization for Economic Co-operation and Development (OECD) countries and high-income countries (non-OECD), respectively. Although technology advancement always promotes CO2 emissions in middle- and low-income countries, its marginal effect is decreasing. This study not only indicates the dynamic impacts of technology advancement on CO2 emissions in different countries, but also contributes to policymakers' understanding of the "common but differentiated responsibilities" involved in mitigating CO2 emissions.

Integrating the MCR and DOI models to construct an ecological security network for the urban agglomeration around Poyang Lake, China.

The development of urban agglomeration in aquatic areas is premised on ecological security. The construction of ecological security network is an effective measure to reduce ecological resistance and guarantee economic development. In this study, a comprehensive ecological security network (ESN) evaluation approach is developed by integrating the Minimum Cumulative Resistance (MCR) model and Duranton and Overman Index (DOI). Taking the urban agglomeration around Poyang Lake in 2015 as a case, the MCR model showed the ecological landscape pattern of discrete connection and large overall ecological resistance. The DOI model indicated that the industries of moderately polluted were global localization, while heavily polluted were small-scale localization and large-scale dispersion. Accordingly, the ESN consisting of 35 ecological sources, 34 ecological corridors, 57 artificial corridors, and 39 eco-economic strategic nodes can avoid the threat of industrial layout to the ecological landscape. The results of this study complemented the guidance of industrial agglomeration theory on the basis of "source-sink" theory. The dual evaluation approach of landscape ecology and economic agglomeration proposed in this study explores interdisciplinary data fusion of different scales, and also provides a reference for inter-municipal coordinated ecological management and restraining urban excessive expansion.

Coexistence of urogenital malformations in a female fetus with de novo 15q24 microdeletion and a literature review.

BACKGROUND: 15q24 microdeletion is a relatively new syndrome caused by nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) in the 15q24 chromosome region. This syndrome is characterized by a spectrum of clinical symptoms including global developmental delay, intellectual disability, facial dysmorphisms, and congenital malformations of the extremities, eye, gastrointestinal tract, genitourinary system, and genitalia. METHOD: Molecular cytogenetic analysis was performed using whole genome single-nucleotide polymorphism (SNP) microarray analysis. Autopsy examination including gross and microscopic examination were performed. In addition, a thorough review of the literature on 15q24 microdeletion was completed and summarized in table format. RESULT: Molecular cytogenetic analysis revealed a 3.88 MB interstitial deletion within 15q24.1 to 15q24.3 (74,353,735-78,228,485 bp) in our case. Autopsy examination showed congenital malformations within the genitourinary system and genitalia, including left kidney agenesis and uterus didelphys. After thorough literature review, we found a series of midline defects associated with 15q24 microdeletion syndrome. CONCLUSION: We report the first case of coexistence of urogenital abnormalities, including left kidney agenesis and uterus didelphys, with 15q24 microdeletion syndrome, which is also associated with midline defects secondary to abnormal development. Since 15q24 microdeletion syndrome is a relatively new entity, fully characterizing its variation and severity requires additional examination of the genetics, molecular profile and structural and functional abnormalities in affected patients. Due to the limited data in the literature, statistical analysis of abnormalities in each organ system is not possible. However, we can predict that novel genetic pathways involving cell migration, adhesion, apoptosis, and embryo development might be discovered with the advanced study of 15q24 microdeletion syndrome.

Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DupA and DupB.

The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophila. Here, we describe identification of two bacterial effectors that reverse PR ubiquitination and are thus named deubiquitinases for PR ubiquitination (DUPs; DupA and DupB). Structural analyses revealed that DupA and SidE ubiquitin ligases harbor a highly homologous catalytic phosphodiesterase (PDE) domain. However, unlike SidE ubiquitin ligases, DupA displays increased affinity to PR-ubiquitinated substrates, which allows DupA to cleave PR ubiquitin from substrates. Interfering with DupA-ubiquitin binding switches its activity toward SidE-type ligase. Given the high affinity of DupA to PR-ubiquitinated substrates, we exploited a catalytically inactive DupA mutant to trap and identify more than 180 PR-ubiquitinated host proteins in Legionella-infected cells. Proteins involved in endoplasmic reticulum (ER) fragmentation and membrane recruitment to Legionella-containing vacuoles (LCV) emerged as major SidE targets. The global map of PR-ubiquitinated substrates provides critical insights into host-pathogen interactions during Legionella infection.

Angiotensin-converting enzyme inhibitors attenuated advanced glycation end products-induced renal tubular hypertrophy via enhancing nitric oxide signaling.

Advanced glycation end products (AGE) and angiotensin II were closely correlated with the progression of diabetic nephopathy (DN). Nitric oxide (NO) is a protective mediator of renal tubular hypertrophy in DN. Here, we examined the molecular mechanisms of angiotensin-converting enzyme inhibitor (ACEI) and NO signaling responsible for diminishing AGE-induced renal tubular hypertrophy. In human renal proximal tubular cells, AGE decreased NO production, inducible NOS activity, guanosine 3',5'-cyclic monophosphate (cGMP) synthesis, and cGMP-dependent protein kinase (PKG) activation. All theses effects of AGE were reversed by treatment with ACEIs (captopril and enalapril), the NO donor S-nitroso-N-acetylpenicillamine (SNAP), and the PKG activator 8-para-chlorophenylthio-cGMPs (8-pCPT-cGMPs). In addition, AGE-enhanced activation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) were clearly reduced by captopril, enalapril, SNAP, and 8-pCPT-cGMPs. The abilities of ACEIs and NO/PKG activation to inhibit AGE-induced hypertrophic growth were verified by the observation that captopril, enalapril, SNAP, and 8-pCPT-cGMPs decreased protein levels of fibronectin, p21 Waf1/Cip1 , and receptor for AGE. The results of the present study suggest that ACEIs significantly reduced AGE-increased ERK/JNK/p38 MAPK activation and renal tubular hypertrophy partly through enhancement of the NO/PKG pathway.