Dynamic Response Characteristics of Shallow Groundwater Level to Hydro-Meteorological Factors and Well Irrigation Water Withdrawals under Different Conditions of Groundwater Buried Depth

Many irrigation districts along the Yellow River have been suffering shallow groundwater depression and agriculture-use water shortage. For comprehending response relationships of shallow groundwater level and various factors under different conditions of groundwater buried depth, the hydro-meteorological time series and the agricultural production data in Puyang area of Henan Province, China during 2006–2018 were collected for performing wavelet analysis of the relationship between the groundwater level and the four different factors, such as precipitation, air temperature, water stage of the Yellow River, and well irrigation water amount. It is shown that when the burial depth of groundwater varied from 0–10 m to over 10 m, the groundwater level was related with both the precipitation and air temperature from moderately to weakly and the delayed response times of the groundwater level to them extended from 2–4 months to more than 5 months. The groundwater level maintained a medium correlation with the well irrigation water amount as the burial depth increased, but the lag response time of groundwater level to well irrigation dramatically decreased when the burial depth exceeded 10 m. The dynamic response relationship between the groundwater and the water stage of the Yellow River was mainly affected by the distance away from the Yellow River rather than the burial depth and the influence of the river stage on the groundwater level was limited within the distance approximate to 20 km away from the Yellow River. The findings are expected to provide the reference for groundwater level prediction and groundwater resources protection

Occurrence Characteristics of Inorganic Nitrogen in Groundwater in Silty-Clay Riparian Hyporheic Zones under Tidal Action: A Case Study of the Jingzi River in Shanghai, China

For comprehending the effect of tidal action on nitrogen cycle in silty-clay riparian hyporheic zones, the synchronous monitoring of water level and water quality was carried out along a test transect during a spring tidal period from 21 to 23 October 2021. Moreover, the permeability and chemical composition of soil samples from drilled holes were measured. Subsequently, the spatiotemporal variation of inorganic nitrogen concentrations in the groundwater in the riparian hyporheic zone was investigated during the study period, and the potential reason was discussed. It is shown that the delayed response time of groundwater level in the silty-clay riparian zone to the tide-driven fluctuation of the river stage increased with distance from the shore and reached 3.0 h at the position 3.83 m away from the shore. The continuous infiltration of the river water under tide action contributed to the aerobic and neutral riparian hyporheic zone conductive to nitrification. Within 4 m away from the bank, the dominant inorganic nitrogen form changed from NO3−-N to NH4+-N, upon increasing the distance from the bank. Additionally, the removal of nitrogen could occur in the riparian hyporheic zone with aerobic and neutral environment under the conjoint control of nitrification, microbial assimilation, and aerobic denitrification

Occurrence Characteristics of Inorganic Nitrogen in Groundwater in Silty-Clay Riparian Hyporheic Zones under Tidal Action: A Case Study of the Jingzi River in Shanghai, China

For comprehending the effect of tidal action on nitrogen cycle in silty-clay riparian hyporheic zones, the synchronous monitoring of water level and water quality was carried out along a test transect during a spring tidal period from 21 to 23 October 2021. Moreover, the permeability and chemical composition of soil samples from drilled holes were measured. Subsequently, the spatiotemporal variation of inorganic nitrogen concentrations in the groundwater in the riparian hyporheic zone was investigated during the study period, and the potential reason was discussed. It is shown that the delayed response time of groundwater level in the silty-clay riparian zone to the tide-driven fluctuation of the river stage increased with distance from the shore and reached 3.0 h at the position 3.83 m away from the shore. The continuous infiltration of the river water under tide action contributed to the aerobic and neutral riparian hyporheic zone conductive to nitrification. Within 4 m away from the bank, the dominant inorganic nitrogen form changed from NO3−-N to NH4+-N, upon increasing the distance from the bank. Additionally, the removal of nitrogen could occur in the riparian hyporheic zone with aerobic and neutral environment under the conjoint control of nitrification, microbial assimilation, and aerobic denitrification

R-loopBase: a knowledgebase for genome-wide R-loop formation and regulation.

R-loops play versatile roles in many physiological and pathological processes, and are of great interest to scientists in multiple fields. However, controversy about their genomic localization and incomplete understanding of their regulatory network raise great challenges for R-loop research. Here, we present R-loopBase (https://rloopbase.nju.edu.cn) to tackle these pressing issues by systematic integration of genomics and literature data. First, based on 107 high-quality genome-wide R-loop mapping datasets generated by 11 different technologies, we present a reference set of human R-loop zones for high-confidence R-loop localization, and spot conservative genomic features associated with R-loop formation. Second, through literature mining and multi-omics analyses, we curate the most comprehensive list of R-loop regulatory proteins and their targeted R-loops in multiple species to date. These efforts help reveal a global regulatory network of R-loop dynamics and its potential links to the development of cancers and neurological diseases. Finally, we integrate billions of functional genomic annotations, and develop interactive interfaces to search, visualize, download and analyze R-loops and R-loop regulators in a well-annotated genomic context. R-loopBase allows all users, including those with little bioinformatics background to utilize these data for their own research. We anticipate R-loopBase will become a one-stop resource for the R-loop community

Taming ROS: Mitochondria-Targeted AIEgen for Neuron Protection via Photosensitization-Triggered Autophagy

Oxidative damages lead to accumulated harmful wastes, which in turn aggravate the related diseases and ROS imbalance. Therefore, provoking the defense system against severe oxidation and maintaining ROS homeostasis are desired. Herein, we used a mitochondria-targeted aggregation-induced emission luminogen (AIEgen) as a phototherapy agent for neuron protection by virtue of its efficient ROS generation in aggregates and mitochondrial delivery. It is demonstrated that controllable ROS generation within mitochondria can trigger defensive autophagy against oxidative damages in neuron cells. This work not only verifies the concept that taming ROS can be used for cell protection, but also provides a promising method to trigger autophagy against destructive oxidation, displaying broad prospects for alleviating oxidation-related diseases and promoting cell-based therapy. </div

The potential of swine pseudorabies virus attenuated vaccine for oncolytic therapy against malignant tumors

Abstract Background Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. Methods PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. Results Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve (“cold”) to inflamed (“hot”), thereby increasing immune cell infiltration and restoring CD8+ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. Conclusions PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8+ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors

Assessing heterogeneity of patient and health system delay among TB in a population with internal migrants in China

BackgroundsThe diagnostic delay of tuberculosis (TB) contributes to further transmission and impedes the implementation of the End TB Strategy. Therefore, we aimed to describe the characteristics of patient delay, health system delay, and total delay among TB patients in Shanghai, identify areas at high risk for delay, and explore the potential factors of long delay at individual and spatial levels.MethodThe study included TB patients among migrants and residents in Shanghai between January 2010 and December 2018. Patient and health system delays exceeding 14 days and total delays exceeding 28 days were defined as long delays. Time trends of long delays were evaluated by Joinpoint regression. Multivariable logistic regression analysis was employed to analyze influencing factors of long delays. Spatial analysis of delays was conducted using ArcGIS, and the hierarchical Bayesian spatial model was utilized to explore associated spatial factors.ResultsOverall, 61,050 TB patients were notified during the study period. Median patient, health system, and total delays were 12 days (IQR: 3–26), 9 days (IQR: 4–18), and 27 days (IQR: 15–43), respectively. Migrants, females, older adults, symptomatic visits to TB-designated facilities, and pathogen-positive were associated with longer patient delays, while pathogen-negative, active case findings and symptomatic visits to non-TB-designated facilities were associated with long health system delays (LHD). Spatial analysis revealed Chongming Island was a hotspot for patient delay, while western areas of Shanghai, with a high proportion of internal migrants and industrial parks, were at high risk for LHD. The application of rapid molecular diagnostic methods was associated with reduced health system delays.ConclusionDespite a relatively shorter diagnostic delay of TB than in the other regions in China, there was vital social-demographic and spatial heterogeneity in the occurrence of long delays in Shanghai. While the active case finding and rapid molecular diagnosis reduced the delay, novel targeted interventions are still required to address the challenges of TB diagnosis among both migrants and residents in this urban setting

Data_Sheet_1_Assessing heterogeneity of patient and health system delay among TB in a population with internal migrants in China.docx

BackgroundsThe diagnostic delay of tuberculosis (TB) contributes to further transmission and impedes the implementation of the End TB Strategy. Therefore, we aimed to describe the characteristics of patient delay, health system delay, and total delay among TB patients in Shanghai, identify areas at high risk for delay, and explore the potential factors of long delay at individual and spatial levels.MethodThe study included TB patients among migrants and residents in Shanghai between January 2010 and December 2018. Patient and health system delays exceeding 14 days and total delays exceeding 28 days were defined as long delays. Time trends of long delays were evaluated by Joinpoint regression. Multivariable logistic regression analysis was employed to analyze influencing factors of long delays. Spatial analysis of delays was conducted using ArcGIS, and the hierarchical Bayesian spatial model was utilized to explore associated spatial factors.ResultsOverall, 61,050 TB patients were notified during the study period. Median patient, health system, and total delays were 12 days (IQR: 3–26), 9 days (IQR: 4–18), and 27 days (IQR: 15–43), respectively. Migrants, females, older adults, symptomatic visits to TB-designated facilities, and pathogen-positive were associated with longer patient delays, while pathogen-negative, active case findings and symptomatic visits to non-TB-designated facilities were associated with long health system delays (LHD). Spatial analysis revealed Chongming Island was a hotspot for patient delay, while western areas of Shanghai, with a high proportion of internal migrants and industrial parks, were at high risk for LHD. The application of rapid molecular diagnostic methods was associated with reduced health system delays.ConclusionDespite a relatively shorter diagnostic delay of TB than in the other regions in China, there was vital social-demographic and spatial heterogeneity in the occurrence of long delays in Shanghai. While the active case finding and rapid molecular diagnosis reduced the delay, novel targeted interventions are still required to address the challenges of TB diagnosis among both migrants and residents in this urban setting.</p