Design, Synthesis, and Biological Evaluation of 1,2,4-Oxadiazole Derivatives Containing an Aryl Carboxylic Acid Moiety as Potent Sarbecovirus Papain-like Protease Inhibitors.

Papain-like protease (PLpro) is a promising therapeutic target for its pivotal role in the life cycle of SARS-CoV-2. A series of 1,2,4-oxadiazole derivatives was designed and synthesized via a ring formation strategy based on SARS-CoV-2 PLpro-GRL0617 complex structure. Systematic structure-activity relationship studies revealed that introducing oxadiazole and aryl carboxylic acid moieties to GRL0617 enhanced the enzymatic inhibition activity, affinity, and deubiquitination capacity toward PLpro. 1,2,4-Oxadiazole compounds 13f and 26r, which had PLpro inhibition activity (IC50 = 1.8 and 1.0 µM) and antiviral activity against SARS-CoV-2 (EC50 = 5.4 and 4.3 µM), exhibited good metabolic stability (t1/2 > 93.2 min) and higher plasma exposure (AUC0-t = 17,380.08 and 24,289.76 ng·h/mL) in mice. Especially, compound 26r with moderate oral bioavailability of 39.1% and potent antiviral activity is worthy of further studies in vivo. Our findings provide a new insight for the discovery of antiviral agents targeting PLpro.

Recent Advances of Food Hazard Detection Based on Artificial Nanochannel Sensors.

Food quality and safety are related to the health and safety of people, and food hazards are important influencing factors affecting food safety. It is strongly necessary to develop food safety rapid detection technology to ensure food safety. As a new detection technology, artificial nanochannel-based electrochemical and other methods have the advantages of being real-time, simple, and sensitive and are widely used in the detection of food hazards. In this paper, we review artificial nanochannel sensors as a new detection technology in food safety for different types of food hazards: biological hazards (bacteria, toxins, viruses) and chemical hazards (heavy metals, organic pollutants, food additives). At the same time, we critically discuss the advantages and disadvantages of artificial nanochannel sensor detection, as well as the restrictions and solutions of detection, and finally look forward to the challenges and development prospects of food safety detection technology based on the limitations of artificial nanochannel detection. We expect to provide a theoretical basis and inspiration for the development of rapid real-time detection technology for food hazards and the production of portable detection equipment in the future.

Electrochemically Dealloying Engineering toward Integrated Monolithic Electrodes with Superior Electrochemical Li-Storage Properties.

Integrated monolithic electrodes (IMEs) free of inactive components demonstrate great potential in boosting energy-power densities and cycling life of lithium-ion batteries. However, their practical applications are significantly limited by low active substance loading (< 4.0 mg cm-2 and 1.0 g cm-3), complicated manufacturing process, and high fabrication cost. Herein, employing industrial Cu-Mn alloy foil as a precursor, a simple neutral salt solution-mediated electrochemical dealloying strategy is proposed to address such problems. The resultant Cu-Mn IMEs achieve not only a significantly larger active material loading due to the in situ generated Cu2O and MnOx (ca. 16.0 mg cm-2 and 1.78 g cm-3), simultaneously fast transport of ions and electrons due to the well-formed nanoporous structure and built-in Cu current collector, but also high structural stability due to the interconnected ligaments and suitable free space to relieve the volume expansion upon lithiation. As a result, they demonstrate remarkable performances including large specific capacities (> 5.7 mAh cm-2), remarkable pseudocapacitive effect despite the battery-type constitutes, long cycling life, and good working condition in a lithium-ion full cell. This study sheds new light on the further development of IMEs, enriches the existing dealloying techniques, and builds a bridge between the two.

Visible Light-Gating Responsive Nanochannel for Controlled Release of the Fungicide.

Fungicides have been widely used to protect crops from the disease of pythium aphanidermatum (PA). However, excessive use of synthetic fungicides can lead to fungal pathogens developing microbicide resistance. Recently, biomimetic nano-delivery systems have been used for controlled release, reducing the overuse of fungicides, and thereby protecting the environment. In this paper, inspired by chloroplast membranes, visible light biomimetic channels are constructed by using retinal, the main component of green pigment on chloroplasts in plants, which can achieve the precise controlled release of the model fungicide methylene blue (MB). The experimental results show that the biomimetic channels have good circularity after and before light conditions. In addition, it is also found that the release of MB in visible light by the retinal-modified channels is 8.78 µmol·m-2·h-1, which is four times higher than that in the before light conditions. Furthermore, MB, a bactericide drug model released under visible light, can effectively inhibit the growth of PA, reaching a 97% inhibition effect. The biomimetic nanochannels can realize the controlled release of the fungicide MB, which provides a new way for the treatment of PA on the leaves surface of cucumber, further expanding the application field of biomimetic nanomembrane carrier materials.

Brain Immune Cell Infiltration and Serum Metabolomic Characteristics Reveal that Lauric Acid Promotes Immune Cell Infiltration in Brain and Streptococcus suis Meningitis in Mice.

Although naturally Streptococcus suis serotype 2 (SS2) causes meningitis resulting in death or sequela of neurological symptoms in pigs and humans, severely threatening public health in the world, it has been difficult to build up and confirm experimental meningitis mouse models with obvious neurological syndrome for about two decades, which strongly hampers the in-depth study on the control measures and mechanisms of SS2-induced meningitis. In this study, a typical meningitis mouse model of SS2 was successfully established, as confirmed by the behavioral indicators of balance beam test, suspension test, and gait analysis. With bacteria gathering in the brain, distinguishable unique features including meningeal thickening, vacuolization of the Nissl body, brain barrier damage, glial cell activation, and more infiltration of T cells, macrophages, and DCs are observed in SS2 meningitis mice with typical neurological signs. Some meningitis mice were also accompanied by identical nephritis, ophthalmia, and cochlearitis. Investigation of the metabolic features demonstrated the downregulated cholic acid and upregulated 2-hydroxyvaleric acid, tetrahydrocortisone, nicotinic acid, and lauric acid in blood serum of mice and piglets with meningitis. And feeding trials show that lauric acid can promote meningitis by promoting the infiltration of immune cells into brain. These findings demonstrated that infection of ICR (improved castle road) mice with SS2 was able to induce typical meningitis accompanied by immune cell infiltration and lauric acid upregulation. These data provide a basis for the deep study of SS2 meningitis.

Wearable-Sensor-Based Weakly Supervised Parkinson's Disease Assessment with Data Augmentation.

Parkinson's disease (PD) is the second most prevalent dementia in the world. Wearable technology has been useful in the computer-aided diagnosis and long-term monitoring of PD in recent years. The fundamental issue remains how to assess the severity of PD using wearable devices in an efficient and accurate manner. However, in the real-world free-living environment, there are two difficult issues, poor annotation and class imbalance, both of which could potentially impede the automatic assessment of PD. To address these challenges, we propose a novel framework for assessing the severity of PD patient's in a free-living environment. Specifically, we use clustering methods to learn latent categories from the same activities, while latent Dirichlet allocation (LDA) topic models are utilized to capture latent features from multiple activities. Then, to mitigate the impact of data imbalance, we augment bag-level data while retaining key instance prototypes. To comprehensively demonstrate the efficacy of our proposed framework, we collected a dataset containing wearable-sensor signals from 83 individuals in real-life free-living conditions. The experimental results show that our framework achieves an astounding 73.48% accuracy in the fine-grained (normal, mild, moderate, severe) classification of PD severity based on hand movements. Overall, this study contributes to more accurate PD self-diagnosis in the wild, allowing doctors to provide remote drug intervention guidance.

LC-MS/MS analysis of Shenghui decoction component and its effect on learning and memory and neuroprotection in sleep deprivation model mice.

BACKGROUND: In recent years, sleep problems have emerged as a significant factor in the development of diseases that influence cognitive function. The inflammatory response may have a role in the neurobiological processes of sleep deprivation, resulting in impairment of memory and learning. Shenghui Decoction (SHD) is a classic formula in Chinese medicine used to treat forgetfulness and insomnia. However, it remains unclear whether the anti-inflammatory effects of SHD are specifically linked to the inhibition of P2X7R and p38MAPK. METHODS: Analysis of chemical constituents of Shenghui Decoction based on UPLC-Q-TOF-MS / MS. The learning and memory competency of the mice was assessed using the new object recognition and Morris water maze tests. The morphology of hippocampus neurons was observed using HE staining, and the expression of inflammatory factors was measured using ELISA and immunofluorescence. The expression of P2X7R and p38MAPK in the hippocampus was analyzed via real-time PCR and Western blotting. Additionally, the components absorbed into the bloodstream of SHD were analyzed. RESULTS: The study found that SHD contains 47 chemical constituents, including phenolic acids, flavonoids, iridoids, and triterpenoids. In addition, it was observed that SHD significantly improved the learning and memory abilities of the mice. SHD also improved the morphology of hippocampus neurons. The expression of inflammatory factors was decreased in the SHD-treated mice. Additionally, the expression of P2X7R and p38MAPK was decreased in the hippocampus of the SHD-treated mice. Fifteen prototype chemical constituents were detected in blood. CONCLUSIONS: The study suggests that SHD could be a viable treatment for cognitive impairments associated with brain inflammation. The therapeutic effects of SHD are likely due to its chemical components, including phenolic acids, flavonoids, iridoids, and triterpenoids. SHD can improve learning and memory impairment caused by sleep deprivation through the P2X7R/p38MAPK inflammatory signaling pathways.

Exploring pollutant joint effects in disease through interpretable machine learning.

Identifying the impact of pollutants on diseases is crucial. However, assessing the health risks posed by the interplay of multiple pollutants is challenging. This study introduces the concept of Pollutants Outcome Disease, integrating multidisciplinary knowledge and employing explainable artificial intelligence (AI) to explore the joint effects of industrial pollutants on diseases. Using lung cancer as a representative case study, an extreme gradient boosting predictive model that integrates meteorological, socio-economic, pollutants, and lung cancer statistical data is developed. The joint effects of industrial pollutants on lung cancer are identified and analyzed by employing the SHAP (Shapley Additive exPlanations) interpretable machine learning technique. Results reveal substantial spatial heterogeneity in emissions from CPG and ILC, highlighting pronounced nonlinear relationships among variables. The model yielded strong predictions (an R of 0.954, an RMSE of 4283, and an R2 of 0.911) and emphasized the impact of pollutant emission amounts on lung cancer responses. Diverse joint effects patterns were observed, varying in terms of patterns, regions (frequency), and the extent of antagonistic and synergistic effects among pollutants. The study provides a new perspective for exploring the joint effects of pollutants on diseases and demonstrates the potential of AI technology to assist scientific discovery.

Neutrophil extracellular traps in adult diseases and neonatal bacterial infectious diseases: A review.

Neutrophils, the most abundant type of white blood cells, are pivotal in fighting bacterial infections due to their immunological and anti-infection capabilities. In recent years, scientists have discovered a novel mechanism known as neutrophil extracellular traps, which are fibrous networks primarily released by neutrophils that combat bacterial infections. There is a growing interest in studying NETs and their role in human infectious diseases, particularly in neonates susceptible to bacterial infections. NETs and their components have been found in various samples from neonatal-infected patients, providing a new route for early diagnosis of neonatal infectious diseases. This paper aims to summarize the studies on NETs in adult diseases and mainly discuss NETs in neonatal sepsis, necrotizing enterocolitis, and purulent meningitis, to provide scientific evidence for early monitoring, diagnosis, and treatment of neonatal infections.

Development and characterization of an active starch-based film as a chlorogenic acid delivery system.

Given its health benefits for the human body, chlorogenic acid (CA) offers promising applications in the food industry. However, the instability and low bioavailability of CA remain to be solved. In this paper, a starch-based film prepared by the homogenization and solution-casting method was used as an effective carrier to alleviate these problems. Homogenization (10-50 MPa) reduced the starch paste viscosity and its particle sizes from 21.64 to 7.68 µm, which promoted the starch recrystallization and induced chemical cross-links between starch-CA, as confirmed by the FTIR result with an appearance of a new CO peak at about 1716 cm-1. Accordingly, the rapidly digestible starch content of the film was reduced to 27.83 % and the CA encapsulation efficiency was increased to 99.08 % (from 65.88 %). As a result, the film system extended CA's release time beyond 4 h and significantly increased the heat-treated CA's antioxidant activity. Besides, the tensile strength and elastic modulus of the film were also improved to 6.29 MPa (from 1.63 MPa) and 160.98 MPa (from 12.02 MPa), respectively, by homogenization. In conclusion, the developed active starch-based film could be used as an edible film for the production of functional food or active food packaging.

Towards sustainability: An integrated life cycle environmental-economic insight into cow manure management.

Waste management signifies an equilibrium between environmental and economic factors. However, a comprehensive understanding of the integrated life cycle environmental-economic performance of waste management activities remains unclear. To facilitate a systematic linkage between the economic and environmental sectors, a regionalized life cycle assessment-based life cycle costing method was developed based on China's actual status quo. The cow manure utilization was set as an entry point to explored long-term environmental-economic performance of milk production under various manure utilization pathways. The results show that trade-offs were observed between internal and external costs as well as various environmental indicators. The choice of waste utilization is the focal point of environmental-economic trade-offs in the cow raising system. The optimal environmental-economic performance was achieved through the manure fertilizer utilization pathway, yielding a remarkable three-fold increase in marginal environmental benefits. Compared with fertilizer utilization, the manure direct returning to field reduced the carbon footprint by 12% while induced an external cost of $14.3. The wastewater treatment pathway is $ 5.5 lower in internal costs but $ 11.7 higher in external costs than those of fertilizer utilization. Overall, utilizing manure has potential to mitigate the upward trend of carbon footprint and external costs. However, achieving the carbon peak remains a significant challenge. A promising solution is the recycling of straw resources within cropping systems, particularly in hotspot regions (e.g., Inner Mongolia, Heilongjiang, Hebei, and Shandong). A comprehensive analysis of the dynamic interplay between cropping systems and cow raising systems is critical steps towards realizing a carbon-neutral future within the dairy production.

Uncovering the energy-carbon-water footprint of waste rubber recycling: Integrated environmental and economic perspectives.

The commitment to waste management has gained increasing momentum as global waste generation continues to skyrocket and threaten the environment. However, detailed assessments and clear insights remain absent to address the global waste utilization conundrum. This study evaluated the impact-oriented energy, carbon, and water (ECW) footprints of three typical scenarios for a waste recycling activity (i.e., waste rubber recycling) from environmental and economic dimensions, and explored key factors, nexus characteristics, and optimization measures. Results indicated that the rubber powder as an asphalt modifier scenario had a 93% greater environmental impact and 87% higher economic cost compared with the pyrolysis and reclaimed rubber production scenarios. Key processes, such as direct processes, electricity generation, and transportation, were identified as the major contributors to the ECW footprints, with the internal costs of raw materials, equipment, and taxes coupled with the external costs of human health dominating the economic impact. The nexus analysis results highlighted the urgent need to optimize the energy system for waste rubber recycling. Greening the production process revealed the benefits, with natural additives mitigating 85% of the environmental burden and 97% of the external costs compared with conventional additives. Industrial green microgrids, clean energy generation, proximity waste management, and electrified transportation were explored to foster sustainable optimization of waste rubber recycling systems. Moreover, a joint tax-subsidy mechanism for rubber production-recycling systems can stimulate recycling-oriented product design and increase the motivation to recycle waste rubber.

Fine Mapping and Identification of a Candidate Gene for the Glossy Green Trait in Cabbage (Brassica oleracea var. capitata).

In higher plants, cuticular wax deposited on the surface of epidermal cells plays an important role in protecting the plant from biotic and abiotic stresses; however, the molecular mechanism of cuticular wax production is not completely understood. In this study, we identified a glossy green mutant (98-1030gl) from the glaucous cabbage inbred line 98-1030. Scanning electron microscopy indicated that the amount of leaf cuticular wax significantly decreased in 98-1030gl. Genetic analysis showed that the glossy green trait was controlled by a single recessive gene. Bulked segregant analysis coupled with whole genome sequencing revealed that the candidate gene for the glossy green trait was located at 13,860,000-25,070,000 bp (11.21 Mb) on Chromosome 5. Based on the resequencing data of two parents and the F2 population, insertion-deletion markers were developed and used to reduce the candidate mapping region. The candidate gene (Bol026949) was then mapped in a 50.97 kb interval. Bol026949 belongs to the Agenet/Tudor domain protein family, whose members are predicted to be involved in chromatin remodeling and RNA transcription. Sequence analysis showed that a single nucleotide polymorphism mutation (C → G) in the second exon of Bol026949 could result in the premature termination of its protein translation in 98-1030gl. Phylogenetic analysis showed that Bol026949 is relatively conserved in cruciferous plants. Transcriptome profiling indicated that Bol026949 might participate in cuticular wax production by regulating the transcript levels of genes involved in the post-translational cellular process and phytohormone signaling. Our findings provide an important clue for dissecting the regulatory mechanisms of cuticular wax production in cruciferous crops.

Cartilage-inspired terpolymer hydrogel with excellent mechanical properties and superior lubricating ability.

Osteoarthritis (OA), the most common degenerative joint disorder, seriously affects patients' daily activities. Recently, hydrogels, due to their similar structure to articular cartilage, have shown great potential as cartilage-repairing materials. In the present work, we developed a simple process for fabricating terpolymer [P(acrylamide-co-acrylic acid-co-2-acrylamido-2-methyl-1-propanesulfonic acid)/Fe3+] hydrogel [P(AAm-co-AAc-co-AMPS)/Fe3+]. The content of AMPS was found to show a crucial effect on the mechanical and tribological performance of the terpolymer hydrogel. When the content of AMPS was 0.45 mol L-1, the compressive strength, modulus, and friction coefficient of the terpolymer hydrogel were 66.60 ± 1.79 MPa, 2.10 ± 0.16 MPa, and 0.032, respectively. In addition, the hydrogel showed high wear durability and the friction coefficient was as low as 0.038 after 3.6 × 105 sliding cycles.

Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target.

SARS-CoV-2 nsp3 is essential for viral replication and host responses. The SARS-unique domain (SUD) of nsp3 exerts its function through binding to viral and host proteins and RNAs. Herein, we show that SARS-CoV-2 SUD is highly flexible in solution. The intramolecular disulfide bond of SARS-CoV SUD is absent in SARS-CoV-2 SUD. Incorporating this bond in SARS-CoV-2 SUD allowed crystal structure determination to 1.35 Å resolution. However, introducing this bond in SARS-CoV-2 genome was lethal for the virus. Using biolayer interferometry, we screened compounds directly binding to SARS-CoV-2 SUD and identified theaflavin 3,3'-digallate (TF3) as a potent binder, Kd 2.8 µM. TF3 disrupted the SUD-guanine quadruplex interactions and exhibited anti-SARS-CoV-2 activity in Vero E6-TMPRSS2 cells with an EC50 of 5.9 µM and CC50 of 98.5 µM. In this work, we provide evidence that SARS-CoV-2 SUD harbors druggable sites for antiviral development.

Genome-Wide Identification of the U-Box E3 Ubiquitin Ligase Gene Family in Cabbage (Brassica oleracea var. capitata) and Its Expression Analysis in Response to Cold Stress and Pathogen Infection.

Plant U-box E3 ubiquitin ligases (PUBs) play an important role in growth, development, and stress responses in many species. However, the characteristics of U-box E3 ubiquitin ligase genes in cabbage (Brassica oleracea var. capitata) are still unclear. Here, we carry out the genome-wide analysis of U-box E3 ubiquitin ligase genes in cabbage and identify 65 Brassica oleracea var. capitata U-box E3 ubiquitin ligase (BoPUB) genes in the cabbage genome. Phylogenetic analysis indicates that all 65 BoPUB genes are grouped into six subfamilies, whose members are relatively conserved in the protein domain and exon-intron structure. Chromosomal localization and synteny analyses show that segmental and tandem duplication events contribute to the expansion of the U-box E3 ubiquitin ligase gene family in cabbage. Protein interaction prediction presents that heterodimerization may occur in BoPUB proteins. In silico promoter analysis and spatio-temporal expression profiling of BoPUB genes reveal their involvement in light response, phytohormone response, and growth and development. Furthermore, we find that BoPUB genes participate in the biosynthesis of cuticular wax and in response to cold stress and pathogenic attack. Our findings provide a deep insight into the U-box E3 ubiquitin ligase gene family in cabbage and lay a foundation for the further functional analysis of BoPUB genes in different biological processes.

Efficacy and Safety of 1470 nm Diode Laser Enucleation of the Prostate in Elderly Benign Prostatic Hyperplasia Patients.

Objective: The aim of this study was to evaluate efficacy and safety of 1470 nm diode laser enucleation of the prostate (DiLEP) and plasmakinetic resection of the prostate (PKRP) in elderly benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms. Methods: A total of 123 elderly patients with BPH were randomized to undergo either 1470 nm DiLEP or PKRP by means of a random number table from September 2020 to April 2022. The perioperative and postoperative data were studied during a 3- and 6-month follow-up. Results: The patients treated with 1470 nm DiLEP had significantly decreased operation time (74.6 ± 17.0 vs 98.8 ± 18.9 minutes, p < 0.001), hemoglobin loss (1.06 ± 0.49 vs 1.59 ± 0.60 g/dL, p < 0.001), bladder irrigation time (22.1 ± 8.1 vs 33.9 ± 10.0 hours, p < 0.001), catheter duration (3.2 ± 1.3 vs 5.8 ± 1.0 days, p < 0.001), and hospital stay (7.6 ± 1.4 vs 9.6 ± 1.3 days, p < 0.001) compared with the PKRP group. Besides, International Index of Erectile Function-5 score of 1470 nm DiLEP group at postoperative 3- and 6-month follow-up was significantly higher than PKRP group. No differences achieving statistical significance were identified in total prostate-specific antigen, maximum urinary flow rate, International Prostate Symptom Score, quality-of-life score, and the postvoid residual urine volume, transient incontinence, urethral stricture, bladder neck contracture, and retrograde ejaculation at 3- and 6-month follow-up. Conclusions: 1470 nm DiLEP is safer than PKRP, with a smaller effect on sexual function, and it is comparable with the efficacy of PKRP, thus making it more suitable for elderly BPH patients. Clinical Trial Registration number: S2021-463-01.

Adh Promotes Actinobacillus pleuropneumoniae Survival in Porcine Alveolar Macrophages by Inhibiting CHAC2-Mediated Respiratory Burst and Inflammatory Cytokine Expression.

Actinobacillus pleuropneumoniae (A. pleuropneumoniae) causes porcine pleuropneumonia that seriously endangers pig's health. Adh, located in the head region of trimeric autotransporter adhesion of A. pleuropneumoniae, affects bacterial adhesion and pathogenicity. However, how Adh mediates A. pleuropneumoniae immune invasion is still unclear. Here, we established the A. pleuropneumoniae strain L20 or L20 ΔAdh-infected porcine alveolar macrophages (PAM) model, and applied protein overexpression, RNA interference, qRT-PCR, Western blot and immunoflourescence techniques to dissect the effects of Adh on PAM during A. pleuropneumoniae infection. We found that Adh could increase the A. pleuropneumoniae adhesion and intracellular survival in PAM. Gene chip analysis of piglet lungs further showed that Adh significantly induced cation transport regulatory-like protein 2 (CHAC2) expression, whose overexpression suppressed the phagocytic capacity of PAM. Furthermore, CHAC2 overexpression dramatically increased glutathione (GSH) expression, decreased reactive oxygen species (ROS), and promoted A. pleuropneumoniae survival in PAM, while the knockdown of CHAC2 reversed these phenomena. Meanwhile, CHAC2 silence activated the NOD1/NF-κB pathway, resulting in an increase in IL-1ß, IL-6, and TNF-α expression, whereas this effect was weakened by CHAC2 overexpression and addition of NOD1/NF-κB inhibitor ML130. Moreover, Adh enhanced the secretion of LPS of A. pleuropneumoniae, which regulated the expression of CHAC2 via TLR4. In conclusion, through a LPS-TLR4-CHAC2 pathway, Adh inhibits respiratory burst and inflammatory cytokines expression to promote A. pleuropneumoniae survival in PAM. This finding may provide a novel target for the prevention and treatment of A. pleuropneumoniae.

Lipolysis and gestational diabetes mellitus onset: a case-cohort genome-wide association study in Chinese.

BACKGROUND: Genetic knowledge of gestational diabetes mellitus (GDM) in Chinese women is quite limited. This study aimed to identify the risk factors and mechanism of GDM at the genetic level in a Chinese population. METHODS: We conducted a genome-wide association study (GWAS) based on single nucleotide polymorphism (SNP) array genotyping (ASA-CHIA Bead chip, Illumina) and a case-cohort study design. Variants including SNPs, copy number variants (CNVs), and insertions-deletions (InDels) were called from genotyping data. A total of 2232 pregnant women were enrolled in their first/second trimester between February 2018 and December 2020 from Anqing Municipal Hospital in Anhui Province, China. The GWAS included 193 GDM patients and 819 subjects without a diabetes diagnosis, and risk ratios (RRs) and their 95% confidence intervals (CIs) were estimated by a regression-based method conditional on the population structure. The calling and quality control of genotyping data were performed following published guidelines. CNVs were merged into CNV regions (CNVR) to simplify analyses. To interpret the GWAS results, gene mapping and overexpression analyses (ORAs) were further performed to prioritize the candidate genes and related biological mechanisms. RESULTS: We identified 14 CNVRs (false discovery rate corrected P values < 0.05) and two suggestively significant SNPs (P value < 0.00001) associated with GDM, and a total of 19 candidate genes were mapped. Ten genes were significantly enriched in gene sets related to lipase (triglyceride lipase and lipoprotein lipase) activity (LIPF, LIPK, LIPN, and LIPJ genes), oxidoreductase activity (TPH1 and TPH2 genes), and cellular components beta-catenin destruction complex (APC and GSK3B genes), Wnt signalosome (APC and GSK3B genes), and lateral element in the Gene Ontology resource (BRCA1 and SYCP2 genes) by two ORA methods (adjusted P values < 0.05). CONCLUSIONS: Genes related to lipolysis, redox reaction, and proliferation of islet ß-cells are associated with GDM in Chinese women. Energy metabolism, particularly lipolysis, may play an important role in GDM aetiology and pathology, which needs further molecular studies to verify.

How can ecosystem status be more comprehensively reflected? A case study of Jinan City, China.

Ecosystems provide benefits to human well-being, but highly concentrated human activities also cause environmental pressure. Previous studies focused only on one aspect: either ecosystem services (ESs) or ecosystem damage (ED). To provide comprehensive view of ecosystem status in the selected study area, an integrated ecosystem performance analytic framework was established based on the ED-ESs synergistic effect. This study quantitatively analyzed the dynamic variation in ecosystem status from both ED and ESs perspectives with a case study of Jinan City, China, from 2000 to 2020. The results showed that the environmental and economic impacts caused by pollution were 692.87 species.year and $15.58 × 108 in 2020, respectively, and they were mainly derived from energy consumption. Regarding ESs, three regulating services (water retention, soil retention, and carbon sequestration) increased from south to north, whereas material services presented the opposite trend. Ecosystem service value had declined after peaking in 2010 when material services contributed the most. Overall, the Jinan City suffered from ecosystem decline, with ecosystem performance on a downward trend from 2000 to 2020. Finally, the characterization factors of four ESs were appropriately incorporated into the life cycle impact assessment to drive the evolution in ecosystem performance calculations.