EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database.

G-quadruplexes (G4s) are non-canonical four-stranded structures and are emerging as novel genetic regulatory elements. However, a comprehensive genomic annotation of endogenous G4s (eG4s) and systematic characterization of their regulatory network are still lacking, posing major challenges for eG4 research. Here, we present EndoQuad (https://EndoQuad.chenzxlab.cn/) to address these pressing issues by integrating high-throughput experimental data. First, based on high-quality genome-wide eG4s mapping datasets (human: 1181; mouse: 24; chicken: 2) generated by G4 ChIP-seq/CUT&Tag, we generate a reference set of genome-wide eG4s. Our multi-omics analyses show that most eG4s are identified in one or a few cell types. The eG4s with higher occurrences across samples are more structurally stable, evolutionarily conserved, enriched in promoter regions, mark highly expressed genes and associate with complex regulatory programs, demonstrating higher confidence level for further experiments. Finally, we integrate millions of functional genomic variants and prioritize eG4s with regulatory functions in disease and cancer contexts. These efforts have culminated in the comprehensive and interactive database of experimentally validated DNA eG4s. As such, EndoQuad enables users to easily access, download and repurpose these data for their own research. EndoQuad will become a one-stop resource for eG4 research and lay the foundation for future functional studies.

Multidirectional Fate Path Model to Connect Phosphorus Emissions with Freshwater Eutrophication Potential.

Excessive anthropogenic phosphorus (P) emissions put constant pressure on aquatic ecosystems. This pressure can be quantified as the freshwater eutrophication potential (FEP) by linking P emissions, P fate in environmental compartments, and the potentially disappeared fraction of species due to increase of P concentrations in freshwater. However, previous fate modeling on global and regional scales is mainly based on the eight-direction algorithm without distinguishing pollution sources. The algorithm fails to characterize the fate paths of point-source emissions via subsurface pipelines and wastewater treatment infrastructure, and exhibits suboptimal performance in accounting for multidirectional paths caused by river bifurcations, especially in flat terrains. Here we aim to improve the fate modeling by incorporating various fate paths and addressing multidirectional scenarios. We also update the P estimates by complementing potential untreated point-source emissions (PSu). The improved method is examined in a rapidly urbanizing area in Taihu Lake Basin, China in 2017 at a spatial resolution of 100 m × 100 m. Results show that the contribution of PSu on FEP (62.6%) is greater than that on P emissions (58.5%). The FEP is more spatially widely distributed with the improved fate modeling, facilitating targeted regulatory strategies tailored to local conditions.

[Research progress in strigolactones and application prospect in medicinal plants].

Strigolactones(SLs) are a class of sesquiterpenoids derived from the carotenoid biosynthesis pathway with the core carbon skeleton consisting of tricyclic lactone(ABC tricyclic ring) and α,ß-unsaturated furan ring(D ring). SLs are widely distributed in higher plants and are symbiotic signals between plants and Arbuscular mycorrhiza(AM), which play key roles in the evolution of plant colonizing terrestrial habitats. As a new type of plant hormone, SLs possess such important biological functions as inhibiting shoot branching(tillers), regulating root architecture, promoting secondary growth, and improving plant stress resistance. Therefore, SLs have attracted wide attention. The biological functions of SLs are not only closely related to the formation of "excellent shape and quality" of Chinese medicinal materials but also have important practical significance for the production of high-quality medicinal materials. However, SLs have been currently widely studied in model plants and crops such as Oryza sativa and Arabidopsis thaliana, and few related studies have been reported on SLs in medicinal plants, which need to be strengthened. This review focused on the latest research progress in the isolation and identification, biological and artificial synthesis pathways, biosynthesis sites and transport modes, signal transduction pathways and mechanisms, and biological functions of SLs, and prospected the research on the regulation mechanism of SLs in the growth and development of medicinal plants and their related application on targeted regulation of Chinese herbal medicine production, which is expected to provide some references for the in-depth research on SLs in the field of Chinese medicinal resources.

Maintained P2Y12 inhibitor monotherapy after shorter-duration of dual antiplatelet therapy in patients undergoing coronary drug-eluting stents implantation: An updated meta-analysis of randomized trials.

WHAT IS KNOWN AND OBJECTIVE: It is well known that high in-stent thrombotic risk due to the superimposition of a platelet-rich thrombus was considered as the main origin of major adverse cardiac events after stent implantation. The clinical management of antiplatelet therapy strategy after percutaneous coronary intervention (PCI) remains controversial. This study is sought to explore the efficacy and safety of a maintained P2Y12 inhibitor monotherapy after shorter-duration of dual antiplatelet therapy (DAPT) in these patients. METHODS: Medline, Google Scholar, Web of Science, and the Cochrane Controlled Trials Registry were searched online for retrieving eligible citations. A composite of all-cause death, myocardial infarction (MI) and stroke was defined as major adverse cardio- and cerebro-vascular events (MACCE), which is analysed as the primary efficacy endpoint. The risk of bleeding events was chosen as safety endpoint. RESULTS: Five randomized clinical trials (RCT) with 32,143 patients were finally analysed. A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT cloud not only reduce the incidence of MACCE [odds ratios (OR): 0.89, 95% confidence intervals (CI): 0.79-0.99, p = 0.037], but also the bleeding risk (OR 0.61, 95% CI: 0.44-0.85, p = 0.003). No higher incidence of any ischaemic events, including MI, stroke or definite stent thrombosis (ST) was observed with respect to this new antiplatelet therapy option. CONCLUSIONS: A maintained P2Y12 inhibitor monotherapy after shorter-duration of DAPT was suggested as a more preferable antiplatelet therapy option in patients undergoing coronary drug-eluting stents (DES) placement. Larger and more powerful randomized trials with precise sub-analyses are still necessary for further confirming these relevant benefits.

Distribution, abundance, and risk assessment of selected antibiotics in a shallow freshwater body used for drinking water, China.

With rapid improvements in industrialization and urbanization, antibiotics are now extensively used to prevent and treat human and animal diseases and husbandry and aquaculture. Some research has been conducted to assess the environmental distribution and risk level of antibiotics, but their distribution remains largely uncharacterized. Thus, this study investigated the distribution and abundance of 39 antibiotics belonging to five groups, and their associated risks in surface water around Luoma Lake in the north of Jiangsu province, China. Nineteen antibiotics were detected, at a detection frequency (DF) ranging from 2.27% to 100%. The total antibiotics (ΣABs) concentrations ranged from 34.91 to 825.93 ng/L, with a median concentration of 195.45 ng/L. Among these antibiotics, chlortetracycline (DF: 100%; median: 172.02 ng/L) was the dominant antibiotic, accounting for a median percentage of 91.0% of ΣABs concentrations. Spearman rank correlation method found a significant correlation between clindamycin (DF: 72.7%; median: 2.01 ng/L) and lincomycin (DF: 79.5%; median: 4.58 ng/L). The ecological risk quotient (RQ) values for two out of 44 sampling sites were higher than 1, indicating a high risk; 11.4% of the RQ values fell between 0.1 and 1, indicating a medium risk. Moreover, roxithromycin was found to be the dominant contributor to the ecological risk, accounting for a median of 79.7% of ΣABs. However, the total non-carcinogenic (<6.54 × 10-4) and carcinogenic risks (<1.64 × 10-7) of ΣABs were negligible at the detected concentrations.

Intensification of phosphorus cycling in China since the 1600s.

Phosphorus (P) is an essential nutrient for living systems with emerging sustainability challenges related to supply uncertainty and aquatic eutrophication. However, its long-term temporal dynamics and subsequent effects on freshwater ecosystems are still unclear. Here, we quantify the P pathways across China over the past four centuries with a life cycle process-balanced model and evaluate the concomitant potential for eutrophication with a spatial resolution of 5 arc-minutes in 2012. We find that P cycling in China has been artificially intensified during this period to sustain the increasing population and its demand for animal protein-based diets, with continuous accumulations in inland waters and lands. In the past decade, China's international trade of P involves net exports of P chemicals and net imports of downstream crops, specifically soybeans from the United States, Brazil, and Argentina. The contribution of crop products to per capita food P demand, namely, the P directly consumed by humans, declined from over 98% before the 1950s to 76% in 2012, even though there was little change in per capita food P demand. Anthropogenic P losses to freshwater and their eutrophication potential clustered in wealthy coastal regions with dense populations. We estimate that Chinese P reserve depletion could be postponed for over 20 y by more efficient life cycle P management. Our results highlight the importance of closing the P cycle to achieve the cobenefits of P resource conservation and eutrophication mitigation in the world's most rapidly developing economy.

Animal based diets and environment: Perspective from phosphorus flow quantifications of livestock and poultry raising in China.

Identifying the key nodes of the phosphorus flows in animal raising system is fundamental to improve P utilization efficiency and reduce the P contamination. This study established a phosphorus flow analysis model for livestock and poultry raising, depicted P flows for major livestock and poultry under two raising modes, and further analyzed their spatial and temporal distributions. We find that around 15% of P input was transferred into the products, and in P output around 40% lost into the environment in 2015. The P flows have been increasing since 2000, and the main contributor is pigs followed by beef cattle. It should be noticed that P loss from livestock and poultry raising is huge with extensive prospect of recycling in some central provinces of China, and western region where ecological environment is fragile, has a higher P loss rate which need to change the dietary preference and adjust raising structure. As for diets, pork and eggs are better choices than milk or other kinds of meat in terms of reducing the P load, when producing per unit protein or energy. This study contributes to the understanding of P management in husbandry industry, the quantification of environmental loads of animal-based food and the identification of the potential of reducing P loss to realize sustainable utilization of P.

Human Perturbation of the Global Phosphorus Cycle: Changes and Consequences.

The phosphorus (P) cycle is an important Earth system process. While natural P mobilization is slow, humans have been altering P cycle by intensifying P releases from lithosphere to ecosystems. Here, we examined magnitudes of which humans have altered the P cycles by integrating the estimates from recent literatures, and furthermore illustrated the consequences. Based on our synthesis, human alterations have tripled the global P mobilization in land-water continuum and increased P accumulation in soil with 6.9 ± 3.3 Tg-P yr-1. Around 30% of atmospheric P transfer is caused by human activities, which plays a significant role than previously thought. Pathways involving with human alterations include phosphate extraction, fertilizers application, wastes generation, and P losses from cropland. This study highlights the importance of sustainable P supply as a control on future food security because of regional P scarcity, food demand increase and continuously P intensive food production. Besides, accelerated P loads are responsible for enhanced eutrophication worldwide, resulting in water quality impairment and aquatic biodiversity losses. Moreover, the P enrichment can definitely stimulate the cycling of carbon and nitrogen, implying the great need for incorporating P in models predicting the response of carbon and nitrogen cycles to global changes.

Occurrence, distribution and risk assessment of suspected endocrine-disrupting chemicals in surface water and suspended particulate matter of Yangtze River (Nanjing section).

The occurrence and distribution of eight selected endocrine-disrupting chemicals were investigated in samples of surface water and suspended particulate matter (SPM) in Nanjing section of Yangtze River over a year (the flow period, the wet period and the dry period). All target compounds were detected at least once in surface water with 4-tert-butylphenol (4-TBP), nonyphenol (NP) and bisphenol A (BPA) as the dominant compounds, with concentrations in the range of 225-1121ng/L, 1.4-858ng/L and 1.7-563ng/L, respectively. Except for December, all selected compounds for the other sampling times were not found in all sampling points. NP (mean concentration 69.8µg/g) and BPA (mean concentration 51.8µg/g) were also the dominant estrogens in SPM. In addition, the highest total compounds concentrations were found in December in both phases, which could be due to the low flow conditions and temperature during this season. Meanwhile, a significant positive correlation was found between the total compounds concentrations in the water phase and those in SPM phase. Risk assessment based on the calculated risk quotients (RQ) showed that low and moderate risk for the aquatic environment from presence of the target compounds at all sampling points with exception of 4-TBP and NP which might pose a high risk to aquatic organisms.

Comparison of Pediatric Forearm Fracture Fixation Between Single- and Double-Elastic Stable Intramedullary Nailing.

The purpose of this study was to evaluate and compare the outcome of single- and double-elastic stable intramedullary nailing (ESIN) for the treatment of pediatric both-bone forearm fractures. We retrospectively analyzed 49 children with both-bone forearm fractures treated with ESIN. Twenty-four patients were treated with single-ESIN (S-ESIN) to fixate the radius only, and the other 25 patients were treated with double-ESIN (D-ESIN) to fixate the radius and ulna. The duration of surgery, times of fluoroscopy, cost of hospitalization, period of castoff, union time, radiographic outcomes, clinical results, and postoperative complications were compared. The duration of surgery, times of fluoroscopy, and cost of hospitalization were significantly lower in the S-ESIN group; however, the average period of castoff was longer in the S-ESIN group. The incidence of delayed union of the ulna was significantly higher in the D-ESIN than in the S-ESIN group. Although the mean angulation deformity of the ulna in the S-ESIN group was significantly larger than in the D-ESIN group, both of them were acceptable (<10 degrees). Despite this, there was no difference in the loss of forearm motion and complication rates between the 2 groups. In conclusion, our data suggest that S-ESIN to fixate the radius alone remains an equally effective fixation method in the pediatric population compared with both-bone fixation and is our treatment of choice.

An extended anterolateral approach for posterolateral tibial plateau fractures.

PURPOSE: The best approach for treating posterolateral tibial plateau fractures remains controversial. The clinical results of an extended anterolateral approach on such fractures are discussed in this study. METHODS: Between 2010 and 2011, ten patients with posterolateral tibial plateau fracture were treated using an extended anterolateral approach with a proximal tibial locking compression plate. The epidemiological data, operation details, and clinical outcomes over 26.4 ± 2.3 months (range 24-30 months) of follow-up were prospectively collected and analyzed. RESULTS: The average surgical duration was 91.5 ± 18.7 min (range 80-130 min). An anatomic reduction rate of 90 % (9/10) was observed although one patient with a lateral comminuted fracture and dislocation presented a 2-mm joint surface depression postoperatively. The average fracture healing time was 10.6 ± 1.8 weeks (range 8-14 weeks), with an average hospital for special surgery knee score of 95.3 ± 6.5 points (range 80-100 points), an average knee flexion of 119.8° ± 17.2° (range 95°-140°) and an average knee extension of 2.1° ± 2.1° (range 0°-6°). No complications were found. CONCLUSIONS: The extended anterolateral approach with a proximal tibial compression plate offers direct and complete surgical exposure and may provide an effective method for the surgical treatment of posterolateral tibial plateau fractures. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Petrocodonliboensis (Gesneriaceae), a new species from Guizhou, China.

Petrocodonliboensis Sheng H.Tang & Jia W.Yang is a new species of Gesneriaceae from Guizhou, southwestern China. The new taxon has a pale-yellow corolla and is most similar to P.luteoflorus. However, it differs from the latter by having a urceolate (vs. cannulate) corolla tube, an abaxial corolla lip 0.8-1.1 mm (vs. 2-2.2 mm) long, and filaments 1.5-1.7 mm (vs. ca. 7 mm) long that are straight (vs. S-shaped or geniculate near the middle). The new taxon is assessed as "Data Deficient" (DD) according to the IUCN standards.

Prognostic significance of serum dynamin­related protein 1 in patients with heart failure: Findings from a prospective observational study.

Mitochondrial dysfunction plays a critical role in the development and exacerbation of heart failure (HF). Dynamin-related protein 1 (Drp1), a key regulator of mitochondrial fission, influences cardiac energy metabolism. The present study investigated the relationship between serum Drp1 levels and the prognosis of patients with HF across a broad spectrum. Serum Drp1 concentrations were measured using ELISA. The primary outcome was the risk of composite major adverse cardiac events (MACEs), which included instances of cardiac death and HF-related readmissions. To assess the prognostic significance of serum Drp1, a receiver operating characteristic curve was constructed to predict MACE-free survival. Additionally, an optimal threshold value for Drp1 was determined and was used to stratify patients into different risk categories. A total of 256 HF patients were finally included and categorized into two groups based on their serum Drp1 levels, labeled as the low (Drp1 ≤2.66 ng/ml, n=101) and high group (Drp1 >2.66 ng/ml, n=155). Patients with low serum Drp1 concentrations showed impaired heart structure and function, as assessed by echocardiography. The 6-month follow-up results indicated that patients with reduced Drp1 concentrations faced a substantially increased risk of MACEs (21.1% vs. 2.8%; P<0.001). The present study revealed that diminished serum Drp1 concentrations could potentially act as a predictive marker for the prognosis of HF in a broad patient population.

Comprehensive pan-cancer analysis reveals prognostic implications of TMEM92 in the tumor immune microenvironment.

BACKGROUND: Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated. METHODS: In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values. RESULTS: In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context. CONCLUSIONS: These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.

Photocatalytic Bicyclization of Indole-Tethered 1,6-Enynes for Diastereoselective Synthesis of Pyrrolo[3,2,1-jk]carbazoles.

A visible-light-driven photocatalytic protocol is established for the diastereoselective synthesis of pyrrolo[3,2,1-jk]carbazoles via a radical-triggered multicomponent bicyclization reaction starting from readily available indole-tethered 1,6-enynes and α-benzyl-α-bromomalonates under mild conditions. This photocatalytic approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and boasts the benefit of efficient ring formation and chemical bond creation.

Photocatalytic Thio/Selenosulfonylation-Bicyclization of Indole-Tethered 1,6-Enynes Leading to Substituted Benzo[c]pyrrolo[1,2,3-lm]carbazoles.

The photocatalyzed radical-triggered thio/selenosulfonylation-bicyclization of indole-tethered 1,6-enynes has been established for the first time, enabling the synthesis of various previously unreported thio/selenosulfonylated benzo[c]pyrrolo[1,2,3-lm]carbazoles with moderate to good yields under mild conditions. The reaction pathway was proposed, consisting of energy transfer, homolytic cleavage, radical addition, 5-exo-dig, radical coupling, and a Mallory reaction cascade. This approach exhibits a wide substrate compatibility and excellent tolerability toward various functional groups and is characterized by its remarkable efficiency in both bond formation and annulation.

[Survey on human soil-borne nematode infection in Xining City].

Five fields were selected from Xining City by stratified cluster sampling method for the survey. 4589 people above 3 years old were examined for nematode infections using Kato-Katz method and children under 12 years old were detected for pinworm infection using transparent tape method from June to August in 2011. The results showed that the total nematode infection rate was 3.0% (136/4 589) with the highest of 3.8% (123/3284) in rural area. The major species was Ascaris lumbricoides, and the infection rate in 15-20 age group was 1.5% (4/264), which was significantly lower than that of the age groups of 60-70 (6.9%, 23/335), above 70 (5.3%, 6/114) and of 10-15 (5.1%, 19/372)(P<0.05). The prevalence of A. lumbricoides among the preschool children (9.5%, 12/127) was statistically higher than those in other occupation groups (P<0.05), and the infection rate showed no statistical significance by gender, ethnic and degree of education (P>0.05). Pinworm infection in children under 12 years old was only 0.5% (2/437).

Key influencing factors of vertical integration of electronic health records in medical consortiums.

BACKGROUND: Similar to other countries around the world, China has incorporated the recording of electronic health data into its national strategy. After the completion of the decentralized construction phase, the construction of electronic health records in China has reached the stages of integration, sharing, and utilization. "Vertical integration" is the premise and foundation of "shared utilization" of electronic health records within the medical consortium, but it is also a bottleneck in realizing this goal. OBJECTIVE: The main purpose of this paper is to find out the key factors affecting the vertical integration of electronic health records in the medical consortiums, and to clarify the impact mechanism of these key factors, so as to provide reference for improving relevant policies. METHODS: In this study, an index system of influencing factors is established for cross-institutional vertical integration of electronic health records within a medical consortium, identifying key influencing factors using the combined fuzzy-DEMATEL-ASIM method and revealing the influence relationship and action mechanism among the key influencing factors using a multi-layer hierarchical influence structure model. RESULTS: There are 32 factors influencing the vertical integration of electronic health records in the medical consortium, 17 of which are key factors. According to the hierarchical structure of key influencing factors, they can be divided into three categories: surface-level factors, middle-level factors and deep-level factors. CONCLUSIONS: In practice, these key factors should be prioritized for improvement and optimization to promote integration projects. In the future, we should focus on key influencing factors to precisely implement policies, such as introducing special promotion policies, unifying development planning, changing health insurance payment methods, establishing sharing standards, and raising public awareness.

Incentive mechanism for sharing and using EHR in medical consortiums based on performance evaluation.

Background: The construction of medical consortiums not only promotes active cooperation among hospitals, but also further intensifies active competition among them. The shared use of electronic health records (EHR) breaks the original pattern of benefit distribution among hospitals. Objective: The purpose of this paper is to establish an incentive mechanism for the shared use EHR, and to reveal the incentive effect and mechanism of key factors, and to put forward management suggestions for solving the real conflicts. Methods: We constructed a basic incentive model and an incentive model that introduces performance evaluation as a supervisory signal, based on analyzing the hospital cost function, the hospital benefit function, and the incentive contract function. Finally, the incentive effects of key factors before and after the introduction of performance evaluation were verified and compared using MATLAB simulation method. Results: The profit level and incentive coefficient of hospitals sharing EHR are independent of the amount of one-time government subsidies. Regardless of whether a performance evaluation supervisory signal is introduced or not, the incentive coefficients are increasing functions with respect to ρ, τ, but decreasing functions with respect to ß, δ, γ. After the inclusion of supervisory signal of performance evaluation in the model, the ability of hospitals to use EHR has a higher impact effectiveness on improving both incentive effects and benefit levels. The impact of the value-added coefficient on the level of earnings is consistently greater than it would have been without the inclusion of the performance evaluation supervisory signal. Conclusions: Enhancing the capacity of hospitals to use EHR and tapping and expanding the value-added space of EHR are 2 key paths to promote sustainable shared use of EHR. Substantive performance evaluation plays an important role in stabilizing incentive effects.

In vivo dynamics and regulation of DNA G-quadruplex structures in mammals.

G-quadruplex (G4) is a four-stranded helical DNA secondary structure formed by guanine-rich sequence folding, and G4 has been computationally predicted to exist in a wide range of species. Substantial evidence has supported the formation of endogenous G4 (eG4) in living cells and revealed its regulatory dynamics and critical roles in several important biological processes, making eG4 a regulator of gene expression perturbation and a promising therapeutic target in disease biology. Here, we reviewed the methods for prediction of potential G4 sequences (PQS) and detection of eG4s. We also highlighted the factors affecting the dynamics of eG4s and the effects of eG4 dynamics. Finally, we discussed the future applications of eG4 dynamics in disease therapy.