Spatio-temporal evolution mechanism and dynamic simulation of nitrogen and phosphorus pollution of the Yangtze River economic Belt in China.

Excess nitrogen and phosphorus inputs are the main causes of aquatic environmental deterioration. Accurately quantifying and dynamically assessing the regional nitrogen and phosphorus pollution emission (NPPE) loads and influencing factors is crucial for local authorities to implement and formulate refined pollution reduction management strategies. In this study, we constructed a methodological framework for evaluating the spatio-temporal evolution mechanism and dynamic simulation of NPPE. We investigated the spatio-temporal evolution mechanism and influencing factors of NPPE in the Yangtze River Economic Belt (YREB) of China through the pollution load accounting model, spatial correlation analysis model, geographical detector model, back propagation neural network model, and trend analysis model. The results show that the NPPE inputs in the YREB exhibit a general trend of first rising and then falling, with uneven development among various cities in each province. Nonpoint sources are the largest source of land-based NPPE. Overall, positive spatial clustering of NPPE is observed in the cities of the YREB, and there is a certain enhancement in clustering. The GDP of the primary industry and cultivated area are important human activity factors affecting the spatial distribution of NPPE, with economic factors exerting the greatest influence on the NPPE. In the future, the change in NPPE in the YREB at the provincial level is slight, while the nitrogen pollution emissions at the municipal level will develop towards a polarization trend. Most cities in the middle and lower reaches of the YREB in 2035 will exhibit medium to high emissions. This study provides a scientific basis for the control of regional NPPE, and it is necessary to strengthen cooperation and coordination among cities in the future, jointly improve the nitrogen and phosphorus pollution tracing and control management system, and achieve regional sustainable development.

Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.

The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3/METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype are associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation, with increased stability of target mRNAs. In preclinical studies, STM2457 treatment suppresses the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as a therapeutic strategy against neuroblastoma.

Mandibular Body Osteotomy Combined with Sagittal Split Ramus Osteotomy for the Treatment of Severe Skeletal Class â ¢ Malocclusion with Ankylosed Teeth.

This study presents a combination of 2 different surgery procedures performed on the mandible as part of the treatment aiming to improve the facial profile and occlusal function of patients with severe skeletal class Ⅲ malocclusion and bilateral edentulous gaps. The teeth next to the edentulous gaps were found to be ankylosed. Mandibular setback by bilateral sagittal split ramus osteotomies and mandibular body osteotomies, combined with Le Fort Ⅰ level maxillary advancement were performed, since the chief complaint of the patient was a concave profile. As a result, the skeletal class Ⅲ malocclusion had been corrected, a satisfying facial profile had been achieved, and no apparent adverse effect was found. Thus, it has been proved that the combination of sagittal split ramus osteotomy and mandibular body osteotomy is available for correcting skeletal class Ⅲ malocclusion.

Sequencing of N6-methyl-deoxyadenosine at single-base resolution across the mammalian genome.

Although DNA N6-methyl-deoxyadenosine (6mA) is abundant in bacteria and protists, its presence and function in mammalian genomes have been less clear. We present Direct-Read 6mA sequencing (DR-6mA-seq), an antibody-independent method, to measure 6mA at base resolution. DR-6mA-seq employs a unique mutation-based strategy to reveal 6mA sites as misincorporation signatures without any chemical or enzymatic modulation of 6mA. We validated DR-6mA-seq through the successful mapping of the well-characterized G(6mA)TC motif in the E. coli DNA. As expected, when applying DR-6mA-seq to mammalian systems, we found that genomic DNA (gDNA) 6mA abundance is generally low in most mammalian tissues and cells; however, we did observe distinct gDNA 6mA sites in mouse testis and glioblastoma cells. DR-6mA-seq provides an enabling tool to detect 6mA at single-base resolution for a comprehensive understanding of DNA 6mA in eukaryotes.

Enhanced SpO2 estimation using explainable machine learning and neck photoplethysmography.

Reflectance-based photoplethysmogram (PPG) sensors provide flexible options of measuring sites for blood oxygen saturation (SpO2) measurement. But they are mostly limited by accuracy, especially when applied to different subjects, due to the diverse human characteristics (skin colors, hair density, etc.) and usage conditions of different sensor settings. This study addresses the estimation of SpO2 at non-standard measuring sites employing reflectance-based sensors. It proposes an automated construction of subject inclusion-exclusion criteria for SpO2 measuring devices, using a combination of unsupervised clustering, supervised regression, and model explanations. This is perhaps among the first adaptation of SHAP to explain the clusters gleaned from unsupervised learning methods. As a wellness application case study, we developed a pillow-based wearable device to collect reflectance PPGs from both the brachiocephalic and carotid arteries around the neck. The experiment was conducted on 33 subjects, each under totally 80 different sensor settings. The proposed approach addressed the variations of humans and devices, as well as the heterogeneous mapping between signals and SpO2 values. It identified effective device settings and characteristics of their applicable subject groups (i.e., subject inclusion-exclusion criteria). Overall, it reduced the root mean squared error (RMSE) by 16%, compared to an empirical formula and a plain SpO2 estimation model.

Spatiotemporal characteristics and co-effects of air quality and carbon dioxide emissions changes during the COVID-19 epidemic lockdown measures in China.

The COVID-19 pandemic prompted several nations, including China, to enact unprecedented lockdown measures, leading to significant alterations in environmental conditions. Previous studies have solely analysed the impact of lockdown measures on air pollutants or carbon dioxide (CO2) emissions during the COVID-19 pandemic in China, but few have focused on the spatio-temporal change characteristics and synergistic effects between the two. In this study, we constructed a methodological framework to examine the spatiotemporal characteristics and co-effects of air quality (PM2.5, SO2, and NO2) and CO2 changes in 324 prefecture-level cities in China due to the COVID-19 blockade measures from January 24 to April 30, 2020, using the regression discontinuity in time method and co-effect control coordinate system. The results show that a significant improvement in air quality and CO2 emissions during the lockdown period, with notable north‒south heterogeneity. During the major lockdown period (January 24 to February 29), the measures resulted in respective reductions of 5.6%, 16.6%, and 25.1% in the concentrations of SO2, NO2, and CO2 nationwide. The proportions of cities with negative treatment effects on PM2.5, SO2, NO2, and CO2 were 39.20%, 70.99%, 84.6%, and 99.38%, respectively. Provinces where concentrations of CO2 and NO2 declined by over 30% were primarily concentrated in southern areas of the 'Yangtze River Defense Line'. Starting from March, the improvement effect of air quality and CO2 has weakened, and the concentration of air pollutants has rebounded. This study offers crucial insights into the causal effects of lockdown measures on air quality changes, and reveals the synergy between air quality and CO2, thereby providing a reference for devising effective air quality improvement and energy-saving emission reduction strategies.

Insulin desensitization and cell senescence induced by heat stress in pig testicular cell model.

Thermostatic animals need to maintain a stable body temperature. A high-temperature environment can cause body temperature to exceed the range of tolerance of the organism, resulting in a heat stress response. The reproductive organs (such as the testes) are more sensitive to temperature due to their special anatomical location. However, to date, the effect of heat stress on the biological function of insulin in testicular cells has not been revealed. Therefore, the current study established a testis cell model to study the effect of heat stress on the biological activity of insulin. The results showed significant alterations in the insulin-induced intracellular signaling under heat stress conditions. Moreover, the IR-mediated intracellular signaling pathway was significantly downregulated under heat stress conditions. Further studies demonstrated that heat stress led to senescence of testicular cells by Sa-ß-gal staining. Furthermore, the expression of senescence markers (p16 and p21) was increased under heat stress. In addition, heat stress was found to cause oxidative stress in testicular cells, which may be the underlying molecular mechanism by which heat stress changes the signaling properties of insulin. Collectively, the current study showed that heat stress caused alterations in insulin-induced intracellular signaling. Heat stress also induced testicular cell senescence.

High-precision mapping reveals rare N6-deoxyadenosine methylation in the mammalian genome.

N6-deoxyadenosine methylation (6mA) is the most widespread type of DNA modification in prokaryotes and is also abundantly distributed in some unicellular eukaryotes. However, 6mA levels are remarkably low in mammals. The lack of a precise and comprehensive mapping method has hindered more advanced investigations of 6mA. Here, we report a new method MM-seq (modification-induced mismatch sequencing) for genome-wide 6mA mapping based on a novel detection principle. We found that modified DNA bases are prone to form a local open region that allows capture by antibody, for example, via a DNA breathing or base-flipping mechanism. Specified endonuclease or exonuclease can recognize the antibody-stabilized mismatch-like structure and mark the exact modified sites for sequencing readout. Using this method, we examined the genomic positions of 6mA in bacteria (E. coli), green algae (C. reinhardtii), and mammalian cells (HEK239T, Huh7, and HeLa cells). In contrast to bacteria and green algae, human cells possess a very limited number of 6mA sites which are sporadically distributed across the genome of different cell types. After knocking out the RNA m6A methyltransferase METTL3 in mouse ES cells, 6mA becomes mostly diminished. Our results imply that rare 6mA in the mammalian genome is introduced by RNA m6A machinery via a non-targeted mechanism.