Transferability of Machine Learning Models for Geogenic Contaminated Groundwaters.

Machine learning models show promise in identifying geogenic contaminated groundwaters. Modeling in regions with no or limited samples is challenging due to the need for large training sets. One potential solution is transferring existing models to such regions. This study explores the transferability of high fluoride groundwater models between basins in the Shanxi Rift System, considering six factors, including modeling methods, predictor types, data size, sample/predictor ratio (SPR), predictor range, and data informing. Results show that transferability is achieved only when model predictors are based on hydrochemical parameters rather than surface parameters. Data informing, i.e., adding samples from challenging regions to the training set, further enhances the transferability. Stepwise regression shows that hydrochemical predictors and data informing significantly improve transferability, while data size, SPR, and predictor range have no significant effects. Additionally, despite their stronger nonlinear capabilities, random forests and artificial neural networks do not necessarily surpass logistic regression in transferability. Lastly, we utilize the t-SNE algorithm to generate low-dimensional representations of data from different basins and compare these representations to elucidate the critical role of predictor types in transferability.

IGF2BP3-mediated regulation of GLS and GLUD1 gene expression promotes treg-induced immune escape in human cervical cancer.

This study aimed to investigate the impact of IGF2BP3, a well-known m6A modification-related protein, on the metabolic and immune microenvironment of human cervical cancer. Bioinformatics analysis was performed to analyze the expression of IGF2BP3 in various databases, and its findings were validated using human cervical cancer tissue microarrays. We conducted a study to investigate the impact of IGF2BP3 on glutamine metabolism in cervical cancer cells through the application of metabolomics and metabolic flow analysis. Additionally, we explored how cervical cancer cells promote immune escape by secreting glutamine-derived lactate in a 3D culture setting. To identify the specific targets of IGF2BP3 that influence glutamine metabolism in cervical cancer, we employed RIP-seq analysis. IGF2BP3 exhibited high expression levels in multiple cervical cancer datasets, and its expression was significantly associated with the prognosis of cervical cancer patients. In mixed 3D cell cultures of cervical cancer and T cells, IGF2BP3 was found to enhance glutamate and glutamine metabolism in cervical cancer cells by up regulating the expression of GLS and GLUD1 genes. Moreover, it influenced the differentiation of Treg cells by promoting lactate production and secretion in cervical cancer, leading to immune escape. Mechanistic analysis revealed that IGF2BP3 stabilized the mRNA of GLS and GLUD1 genes through m6A modification, thereby facilitating glutamate and glutamine metabolism in cervical cancer cells and regulating lactate production. Additionally, we investigated the correlation between GLS, GLUD1 protein expression, and IGF2BP3 expression in human cervical cancer through multicolor immunofluorescence staining. The relevance of IGF2BP3 in the context of Treg cell-associated immune escape in cervical cancer was also confirmed. IGF2BP3 exhibits high expression in human cervical cancer and plays a crucial role in stabilizing the mRNA of GLS and GLUD1 genes, key metabolic enzymes in glutamate and glutamine metabolism, through m6A modification. This process leads to immune escape in cervical cancer by promoting lactate production and secretion.

Co-occurrence of arsenic and iodine in the middle-deep groundwater of the Datong Basin: From the perspective of optical properties and isotopic characteristics.

Redox processes can induce arsenic (As) and iodine (I) transformation and thus change As and I co-occurrence, yet there is no evidence that Fe-C-S coupled redox processes have such an impact on the co-occurrence of As and I. To fill this gap, middle-deep groundwater from the Datong Basin were samples for the purpose of exploring how dissolved organic matter (DOM) reactivity affects As and I enrichment and how iron reduction and sulfate reduction processes influence As and I co-occurrence. We identified three DOM components: reduced and oxidized quinone compounds (C1 and C3) and a labile DOM from terrestrial inputs (C2). Two pathways of DOM processing take place in the aquifer, including the degradation of labile DOM to HCO3- and the transformation of oxidized quinone compounds to reduced quinone compounds. Electrons transfer drives the reduction of the terminal electron acceptors. The supply of electrons promotes the reduction of iron and sulfate by microbes, enhancing As and I co-enrichment in groundwater. Thus, the reduction processes of iron and sulfate triggered by the dual roles of DOM affect dissolved As and I co-enrichment. As and I biogeochemical cycling interacts with C, Fe, and S cycling. These results provide isotopic and fluorescence evidence that explains the co-occurrence of arsenic and iodine in middle-deep aquifers.

TENT5D disruption causes oligoasthenoteratozoospermia and male infertility.

BACKGROUND: Oligoasthenoteratozoospermia (OAT) is one of the most complex aggregators of male gametic problems. However, the genetic etiology of OAT is still largely unknown. OBJECTIVES: To reveal the new genetic factors responsible for male infertility owning to OAT and reveal the outcomes of the affected patients from intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: Two infertile men with typical OAT were recruited in 2018 and retrospected a cohort that included 47 patients with OAT from 2013 to 2021. Fifty healthy men with proven fertility served as control subjects. To identify the novel pathogenic variants, whole-exome sequencing and Sanger sequencing were used. In silico analysis revealed the affecting of the variants. Field emission scanning electron microscopy was employed to observe the morphological defects of the spermatozoa. Immunofluorescence was used to analyze the expression and localization of the related protein. CRISPR/Cas9 was used to generate the mouse model. ICSI was used as a treatment for the patients and to assess the effects of the pathogenic variant on fertilization and embryo development. RESULTS: We identified a loss-of-function mutation NM_001170574.2:c.823G > T (p.Glu275*) in X-linked TENT5D from two patients with OAT. This variant is highly deleterious and has not been found in the human population. The count of patients' spermatozoa is dramatically decreased and displays multiple morphologic abnormalities with poor motility. Tent5d knockout mice are infertile and exhibit parallel defects. ICSI could rescue the infertility of the Tent5d knockout male mice. Moreover, the proband was treated with ICSI and achieved a successful pregnancy outcome for the first time. Subsequent mutation screening identified no TENT5D mutations among 47 additional patients with OAT and 50 control subjects. CONCLUSION: Mutation in TENT5D results in OAT and male infertility, and this terrible situation could be rescued by ICSI.

Smartphone-based hand-held polarized light microscope for on-site pharmaceutical crystallinity characterization.

Polarized light microscopy (PLM) is a common but critical method for pharmaceutical crystallinity characterization, which has been widely introduced for research purposes or drug testing and is recommended by many pharmacopeias around the world. To date, crystallinity characterization of pharmaceutical solids is restricted to laboratories due to the relatively bulky design of the conventional PLM system, while little attention has been paid to on-site, portable, and low-cost applications. Herein, we developed a smartphone-based polarized microscope with an ultra-miniaturization design ("hand-held" scale) for these purposes. The compact system consists of an optical lens, two polarizers, and a tailor-made platform to hold the smartphone. Analytical performance parameters including resolution, imaging quality of interference color, and imaging reproducibility were measured. In a first approach, we illustrated the suitability of the device for pharmaceutical crystallinity characterization and obtained high-quality birefringence images comparable to a conventional PLM system, and we also showed the great promise of the device for on-site characterization with high flexibility. In a second approach, we employed the device as a proof of concept for a wider application ranging from liquid crystal to environmental pollutants or tissues from plants. As such, this smartphone-based hand-held polarized light microscope shows great potential in helping pharmacists both for research purposes and on-site drug testing, not to mention its broad application prospects in many other fields.

Synthesis of bimetal MOFs for rapid removal of doxorubicin in water by advanced oxidation method.

Doxorubicin (DOX) has been an emerging environmental pollutant due to its significant genotoxicity to mankind. Advanced oxidation processes are a potential strategy to remove DOX in water solution. To develop a highly efficient catalytic agent to remove DOX, bimetal MOFs were synthesized, with Cu2+ and Co2+ as the central ions and adenine as the organic ligand. This study investigated the degradation of DOX by Co/Cu-MOFs combined with peroxymonosulfate (PMS). It was found that the degradation of DOX by Co/Cu-MOFs can reach 80% in only 10 seconds. This can be explained by the charge transfer from Co(iii) to Co(ii) being accelerated by Cu2+, resulting in the rapid generation of free radicals, which was proved by the EIS Nyquist diagram. Co/Cu-MOFs can be reused by simply washing with water without inactivation. Therefore, Co/Cu-MOFs can be used as an efficient catalytic agent to degrade DOX in environmental water.

Starch phosphorylase 2 is essential for cellular carbohydrate partitioning in maize.

Carbohydrate partitioning is essential for plant growth and development, and its hindrance will result in excess accumulation of carbohydrates in source tissues. Most of the related mutants in maize (Zea mays L.) display impaired whole-plant sucrose transport, but other mechanisms affecting carbohydrate partitioning have seldom been reported. Here, we characterized chlorotic leaf3 (chl3), a recessive mutation causing leaf chlorosis with starch accumulation excessively in bundle sheath chloroplasts, suggesting that chl3 is defective in carbohydrate partitioning. Positional cloning revealed that the chl3 phenotype results from a frameshift mutation in ZmPHOH, which encodes starch phosphorylase 2. Two mutants in ZmPHOH exhibited the same phenotype as chl3, and both alleles failed to complement the chl3 mutant phenotype in an allelism test. Inactivation of ZmPHOH in chl3 leaves reduced the efficiency of transitory starch conversion, resulting in increased leaf starch contents and altered carbohydrate metabolism patterns. RNA-seq revealed the transcriptional downregulation of genes related to photosynthesis and carbohydrate metabolism in chl3 leaves compared to the wild type. Our results demonstrate that transitory starch remobilization is very important for cellular carbohydrate partitioning in maize, in which ZmPHOH plays an indispensable role.

The SNP rs516946 Interacted in the Association of MetS with Dietary Iron among Chinese Males but Not Females.

This study aimed to explore the role of the single nucleotide polymorphism (SNP) rs516946 of the Ankyrin 1 (ANK1) gene in the relationship between dietary iron and metabolic syndrome (MetS) in the Chinese population. A total of 2766 Chinese adults (1284 males and 1482 females) were recruited. A 3-day 24-h dietary recall and weighing of household condiments were used to assess dietary intake. Anthropometric and laboratory measurements were obtained. After adjusting for age, region, years of education, intentional physical exercise, physical activity level, smoking, alcohol use and energy intake, dietary iron and the SNP rs516946 were both correlated with MetS risk and interacted among the male participants. The trend between dietary iron and MetS risk remained among T allele non-carriers of males but not among T allele carriers of males. Both the SNP rs516946 and the ferritin level correlated positively with the aspartate aminotransferase (AST) level. ANK1 SNP rs516946 interacted in the association of MetS with dietary iron among Chinese males while no association was found among females. Periodic blood loss might prevent females from these associations. The SNP rs516946 might correlate with liver function.

PHDMF: A Flexible and Scalable Personal Health Data Management Framework Based on Blockchain Technology.

Currently, most of the personal health data (PHD) are managed and stored separately by individual medical institutions. When these data need to be shared, they must be transferred to a trusted management center and approved by data owners through the third-party endorsement technology. Therefore, it is difficult for personal health data to be shared and circulated over multiple medical institutions. On the other hand, the use of directly exchanging and sharing the original data has become inconsistent with the data rapid growth of medical institutions because of the need of massive data transferring across agencies. In order to secure sharing and managing the mass personal health data generated by various medical institutions, a federal personal health data management framework (PHDMF, https://hvic.biosino.org/PHDMF) has been developed, which had the following advantages: 1) the blockchain technology was used to establish a data consortium over multiple medical institutions, which could provide a flexible and scalable technical solution for member extension and solve the problem of third-party endorsement during data sharing; 2) using data distributed storage technology, personal health data could be majorly stored in their original medical institutions, and the massive data transferring process was of no further use, which could match up with the data rapid growth of these institutions; 3) the distributed ledger technology was utilized to record the hash value of data, given the anti-tampering feature of the technology, malicious modification of data could be identified by comparing the hash value; 4) the smart contract technology was introduced to manage users' access and operation of data, which made the data transaction process traceable and solved the problem of data provenance; and 5) a trusted computing environment was provided for meta-analysis with statistic information instead of original data, the trusted computing environment could be further applied to more health data, such as genome sequencing data, protein expression data, and metabolic profile data through combining the federated learning and blockchain technology. In summary, the framework provides a convenient, secure, and trusted environment for health data supervision and circulation, which facilitate the consortium establish over medical institutions and help achieve the value of data sharing and mining.

Tight junction protein CLDN17 serves as a tumor suppressor to reduce the invasion and migration of oral cancer cells by inhibiting epithelial-mesenchymal transition.

OBJECTIVE: To investigate claudin-17 (CLDN17) expression in oral cancer and its effect on epithelial-mesenchymal transition (EMT), invasion and migration in oral cancer cells. METHODS: The GEO2R tool was used to analyze gene expression in two microarray datasets (GSE74530 and GSE146483) derived from the Gene Expression Omnibus (GEO) database. Gene Expression Profiling Interactive Analysis (GEPIA) verified CLDN17 expression in head and neck squamous cell carcinoma (HNSC) patients. Moreover, oral cancer cells were transfected with CLDN17 overexpression plasmid or CLDN17 shRNA to evaluate cell invasion and migration. Gene and protein expression was detected by qRT-PCR, immunohistochemistry and western blotting. RESULTS: CLDN17 was one of the top 200 differentially expressed genes in the GSE74530 and GSE146483 datasets and was downregulated in oral cancer. CLDN17 expression was higher in HNSC tissues, and it was related to TNM staging. In HNSC tumors, CLDN17 expression was positively correlated with CDH1 but negatively related to VIM, SNAIL1, SNAIL2, and TWIST1. Meanwhile, we found that CLDN17 expression was lower in oral cancer tissues; it declined with higher T status, N status, M status and staging, lower differentiation grade, and a worse prognosis. Upregulation of CLDN17 inhibited the invasion and migration of oral cancer cells, with elevated CDH1 and reduced VIM, SNAIL1, SNAIL2, and TWIST1, while CLDN17 downregulation had the opposite effects. CONCLUSION: CLDN17 may serve as a tumor suppressor in oral cancer since it could reduce the invasion and migration of cells by inhibiting the EMT process, thus becoming a potential therapeutic target in oral cancer.

Homozygous mutation in DNALI1 leads to asthenoteratozoospermia by affecting the inner dynein arms.

Asthenozoospermia is the most common cause of male infertility. Dynein protein arms play a crucial role in the motility of sperm flagella and defects in these proteins generally impair the axoneme structure and affect sperm flagella function. In this study, we performed whole exome sequencing for a cohort of 126 infertile patients with asthenozoospermia and identified homozygous DNALI1 mutation in one patient from a consanguineous family. This identified homozygous mutation was verified by Sanger sequencing. In silico analysis showed that this homozygous mutation is very rare, highly pathogenic, and very conserved. Sperm routine analysis confirmed that the motility of the spermatozoa from the patient significantly decreased. Further sperm morphology analysis showed that the spermatozoa from the patient exhibited multiple flagella morphological defects and a specific loss in the inner dynein arms. Fortunately, the patient was able to have his child via intracytoplasmic sperm injection treatment. Our study is the first to demonstrate that homozygous DNALI1 mutation may impair the integration of axoneme structure, affect sperm motility and cause asthenoteratozoospermia in human beings.

Knockdown NRPC2, 3, 8, NRPABC1 and NRPABC2 Affects RNAPIII Activity and Disrupts Seed Development in Arabidopsis.

RNA polymerase III (RNAPIII) contains 17 subunits forming 4 functional domains that control the different stages of RNAPIII transcription and are dedicated to the synthesis of small RNAs such as 5S rRNA and tRNAs. Here, we identified 23 genes encoding these subunits in Arabidopsis (Arabidopsis thaliana) and further analyzed 5 subunits (NRPC2, NRPC3, NRPC8, NRPABC1, and NRPABC2) encoded by 6 genes with different expression patterns and belonging to different sub-complexes. The knockdown of these genes repressed the expression of 5S rRNA and tRNAs, causing seed developmental arrest at different stages. Among these knockdown mutants, RNA-seq analysis revealed 821 common differentially expressed genes (DEGs), significantly enriched in response to stress, abscisic acid, cytokinins, and the jasmonic acid signaling pathway. Weighted gene co-expression network analysis (WGCNA) revealed several hub genes involved in embryo development, carbohydrate metabolic and lipid metabolic processes. We identified numerous unique DEGs between the mutants belonging to pathways, including cell proliferation, ribosome biogenesis, cell death, and tRNA metabolic processes. Thus, NRPC2, NRPC3, NRPC8, NRPABC1, and NRPABC2 control seed development in Arabidopsis by influencing RNAPIII activity and, thus, hormone signaling. Reduced expression of these subunit genes causes an insufficient accumulation of the total RNAPIII, leading to the phenotypes observed following the genetic knockdown of these subunits.

Photo-irradiation tunes highly active sites over ß-Ni(OH)2 nanosheets for the electrocatalytic oxygen evolution reaction.

A facile photo-irradiation method is developed to tune active sites over ß-Ni(OH)2 nanosheets. Photo-irradiated ß-Ni(OH)2 nanosheets possess disordered surface atoms and preferred growth of highly active crystal facets, which exhibit enhanced performance for the electrocatalytic oxygen evolution reaction.

Sports Training Health Analysis Algorithm Based on Heart Rhythm Feature Extraction and Convolutional Neural Network.

Intelligent sports equipment and software have emerged in the field of sports as a result of the advancement of information technology, allowing professional athletes to collect and visually display the movement and physical signs of the human body to aid in the planning of sports strategies. Intuitive data, on the other hand, cannot assist ordinary people who lack professional knowledge in exercising correctly. As a result, in the field of intelligent sports and health, effective use of collected exercise and physical sign data to analyze the user's personal physical condition and generate reasonable exercise suggestions has emerged as a research direction. In humans, the heart sound signal is a biological signal. It can help people detect and monitor heart health problems by analyzing the characteristics of heart sound signals. The goal of this paper is to use heart sound to identify and analyze athletes' training health. It provides a revolutionary health analysis algorithm based on heart rhythm feature extraction and convolutional neural networks, which is based on exercise training. It greatly improves the accuracy of the recognition and prediction of the athlete's training health status.

Lithium doped nickel oxide nanocrystals with a tuned electronic structure for oxygen evolution reaction.

The electronic structure of catalysts influences the electrocatalytic behavior. Herein, the electronic structure of NiO nanocrystals is modified by doping with a small amount of Li+. The Li+ doped NiO nanocrystals show much better OER activity than pristine NiO and LiNiO2, which is a result of tuned Fermi levels, stronger hybridization between Ni 3d and O 2p, and narrowed energy band gap. This work provides a facile strategy to regulate NiO electronic energy bands to promote OER performance.

Degradation of organic dyes by peroxymonosulfate activated with water-stable iron-based metal organic frameworks.

In this study, MIL-101(Fe) is prepared via a facile solvent-thermal method, and then applied as catalyst for activating PMS, thus generating reactive radicals for organic dyes removal in aqueous solution. Rhodamine B (RhB), Malachite Green (MG) and Methylene Blue (MB) were selected as model pollutants. The experiments showed that MIL-101(Fe)/PMS had higher removal efficiency for dyes than MIL-101(Fe), indicating that MIL-101(Fe) can be simultaneously used as adsorbent and PMS-activating catalyst for dyes removal. The effects of initial pH and the coexisted negative ions on MB degradation were further discussed, showing that MIL-101(Fe) can degrade MB with excellent stability. Furthermore, the reactive species in MIL-101(Fe)/PMS system were deduced as sulfate radicals and hydroxyl radicals. Finally, the degradation intermediates and possible degradation pathway were investigated by LC-MS.

Loss of Function of an RNA Polymerase III Subunit Leads to Impaired Maize Kernel Development.

Kernel size is an important factor determining grain yield. Although a number of genes affecting kernel development in maize (Zea mays) have been identified by analyzing kernel mutants, most of the corresponding mutants cannot be used in maize breeding programs due to low germination or incomplete seed development. Here, we characterized small kernel7, a recessive small-kernel mutant with a mutation in the gene encoding the second-largest subunit of RNA polymerase III (RNAPΙΙΙ; NRPC2). A frame shift in ZmNRPC2 leads to a premature stop codon, resulting in significantly reduced levels of transfer RNAs and 5S ribosomal RNA, which are transcribed by RNAPΙΙΙ. Loss-of-function nrpc2 mutants created by CRISPR/CAS9 showed significantly reduced kernel size due to altered endosperm cell size and number. ZmNRPC2 affects RNAPIII activity and the expression of genes involved in cell proliferation and endoreduplication to control kernel development via physically interacting with RNAPIII subunits RPC53 and AC40, transcription factor class C1 and Floury3. Notably, unlike the semidominant negative mutant floury3, which has defects in starchy endosperm, small kernel7 only affects kernel size but not the composition of kernel storage proteins. Our findings provide novel insights into the molecular network underlying maize kernel size, which could facilitate the genetic improvement of maize in the future.

DOX sensitized upconversion metal-organic frameworks for the pH responsive release and real-time detection of doxorubicin hydrochloride.

Drug resistance is a major obstacle in cancer treatment, and designing a material that monitors real-time drug release remains a top priority. In this study, metal-organic frameworks doped with lanthanum and thulium were synthesized and then coated with aminated silica to form La/Tm-MOF@d-SiO2 as a drug carrier. Doxorubicin hydrochloride (DOX) was selected as a drug model, and the drug loading and release were investigated. It was found that the release of DOX under acidic conditions reached an optimal level, indicating the pH-responsiveness of La/Tm-MOF@d-SiO2. Under acidic conditions (pH = 5.8), upconversion fluorescence was generated after loading DOX on La/Tm-MOF@d-SiO2. At pH = 5.8, the longer the drug released, the stronger the upconversion fluorescence. It was found that the upconversion fluorescence intensity is directly proportional to the amount of drug released; thus, the real-time monitoring of DOX release in tumor cells can be performed based on the upconversion fluorescence.

ZmSMK9, a pentatricopeptide repeat protein, is involved in the cis-splicing of nad5, kernel development and plant architecture in maize.

Maize kernel size and weight are essential contributors to its yield. So the identification of the genes controlling kernel size and weight can give us a chance to gain the yield. Here, we identified a small kernel mutant, Zea mays small kernel 9 (Zmsmk9), in maize. Cytological observation showed that the development of the endosperm and embryo was delayed in Zmsmk9 mutants at the early stages, resulting in a small kernel phenotype. Interestingly, despite substantial variation in kernel size, the germination of Zmsmk9 seeds was comparable to that of WT, and could develop into normal plants with upright leaf architecture. We cloned Zmsmk9 via map-based cloning. ZmSMK9 encodes a P-type pentatricopeptide repeat protein that targets to mitochondria, and is involved in RNA splicing in mitochondrial NADH dehydrogenase5 (nad5) intron-1 and intron-4. Consistent with the delayed development phenotype, transcriptome analysis of 12-DAP endosperm showed that starch and zeins biosynthesis related genes were dramatically down regulated in Zmsmk9, while cell cycle and cell growth related genes were dramatically increased. As a result, ZmSMK9 is a novel gene required for the splicing of nad5 intron-1 and intron-4, kernel development, and plant architecture in maize.

Prevalence of gestational diabetes mellitus and associated risk factors in pregnant Chinese women: a cross-sectional study in Huangdao, Qingdao, China.

BACKGROUND AND OBJECTIVES: This study explored the prevalence of gestational diabetes mellitus (GDM) in Chinese pregnant women and identified risk factors for GDM after the implementation of the universal two-child policy. METHODS AND STUDY DESIGN: On the basis of income and population, we randomly selected three hospitals through stratified and cluster sampling. From January 1 to July 31, 2016, 4959 women who had been registered within 12 weeks of gestation received a 75-g 2-h oral glucose tolerance test (OGTT) at 24-28 gestational weeks. International Association of Diabetes and Pregnancy Study Group criteria were used for the diagnosis of GDM. RESULTS: The OGTT was positive in 1080 (21.8%; 1080/4959) women, who were then diagnosed as having GDM on the basis of their results. GDM was positively associated with the following factors: advanced maternal age (p<0.001; adjusted odds ratio [OR]=4.88; 95% confidence interval [CI]=2.38-10.0, pre-pregnancy body mass index overweight (OR=2.44, 95% CI=1.78-3.34)/obesity (OR=10.9, 95% CI=6-19.6; p<0.001), paternal history of diabetes (p=0.003; OR=2.54, 95% CI=1.38-4.67), and maternal history of diabetes (p<0.001; OR=3.6, 95% CI=2.16-5.98). CONCLUSIONS: Qingdao has an exceptionally high estimated prevalence of GDM. Widely recognized risk factors for GDM were advanced age, pre-pregnancy overweight/obesity, and a family history of diabetes in first-degree relatives. More options to prevent and manage GDM must be explored.