Geographic, sex and socioeconomic disparities in esophageal cancer incidence in China: A population-based study.

Geographic and sex differences in esophageal cancer have been reported in China, but data are lacking at the local level. We aimed to investigate geographic and sex disparities in esophageal cancer incidence among Chinese counties and whether county-level socioeconomic status was associated with these variations. We obtained esophageal cancer data from 2015 to 2017 for 782 counties from population-based cancer registries in China. We calculated age-standardized incidence rates and male-to-female incidence rate ratios (IRRs) by county. We performed hotspot analysis to identify geographical clusters. We used negative binomial regression models to analyze the association between incidence rates and county-level socioeconomic factors. There were significant geographic disparities in esophageal cancer incidence, with 8.1 times higher rate in the 90th-percentile county than in the 10th-percentile county (23.7 vs 2.9 per 100 000 person-years). Clusters of elevated rates were prominent across north-central China. Nationally, men had 2.9 times higher incidence of esophageal cancer than women. By county, the male-to-female IRRs ranged from 1.1 to 21.1. Clusters of high male-to-female IRRs were observed in northeast China. Rurality (IRR 1.16, 95% CI 1.10-1.22), per capita gross domestic product (IRR 0.95, 0.92-0.98) and percentage of people with a high school diploma (IRR 0.86, 0.84-0.87) in a county were significantly associated with esophageal cancer incidence. The male-to-female IRRs were higher in counties with higher socioeconomic status. Substantial differences in incidence rates and sex ratios of esophageal cancer exist between Chinese counties, and county-level socioeconomic status was associated with these variations. These findings may inform interventions to reduce these disparities.

The effects of childhood maltreatment, recent interpersonal and noninterpersonal stress, and HPA-axis multilocus genetic variation on prospective changes in adolescent depressive symptoms: A multiwave longitudinal study.

Based on a multiwave, two-year prospective design, this study is the first to examine the extent to which multilocus hypothalamic-pituitary-adrenal axis (HPA axis)-related genetic variants, childhood maltreatment, and recent stress jointly predicted prospective changes in adolescent depressive symptoms. A theory-driven multilocus genetic profile score (MGPS) was calculated to combine the effects of six common polymorphisms within HPA-axis related genes (CRHR1, NR3C1, NR3C2, FKBP5, COMT, and HTR1A) in a sample of Chinese Han adolescents (N = 827; 50.2% boys; Mage = 16.45 ± 1.36 years). The results showed that the three-way interaction of HPA-axis related MGPS, childhood maltreatment and recent interpersonal, but not noninterpersonal, stress significantly predicted prospective changes in adolescent depressive symptoms. For adolescents with high but not low HPA-axis related MGPS, exposure to severe childhood maltreatment predisposed individuals more vulnerable to recent interpersonal stress, exhibiting greater prospective changes in adolescent depressive symptoms. The findings provide preliminary evidence for the cumulative risk mechanism regarding gene-by-environment-by-environment (G × E1 × E2) interactions that underlie the longitudinal development of adolescent depressive symptoms and show effects specific to interpersonal stress.

Domain-limited thermal transformation preparation of novel graphitized carbon-supported layered double oxides for efficient tetracycline degradation.

The resource utilization of industrial lignin to construct high-performance catalysts for wastewater treatment field is pioneering research. Herein, the novel graphitized carbon-supported CuCoAl-layered double oxides (LDOs-GC) were successfully designed by the domain-limited thermal transformation technology using sodium lignosulfonate (LS) self-assembled CuCoAl-layered double hydroxides as the precursor. The optimized LDOs-GC catalyst owned the excellent tetracycline (TC) degradation of 98.0% within 15 min by activated peroxymonosulfate (PMS) under optimal conditions (20 mg/L catalyst, 1.5 mM PMS, 30 mg/L TC). The density of metal ions in the catalyst and the synergistic interaction between graphitized carbon (GC) and metal ions played a major role in TC degradation. Based on a comprehensive analysis, the TC degradation in LDOs-GC/PMS system was proved to be accomplished by a combination of free radicals (SO4·- and HO·) and non-radicals (1O2). Meanwhile, the possible degradation pathways of TC were proposed by the analysis of TC degradation intermediates and a comprehensive analysis of the rational reaction mechanism for TC degradation by LDOs-GC/PMS system was also performed. This work provides a new strategy for developing novel high-performance catalysts from industrial waste, while offering a green, cheap and sustainable approach to antibiotic degradation.

Impacts of climate change on winter wheat net primary production: the regulatory role of crop management.

BACKGROUND: The Huang-Huai-Hai Plain (3HP) is the main agricultural area in China. Although climate change (CC) and crop management (CM) are considered factors affecting the winter wheat net primary production (NPP) in this region, their effects remain unclear. In the present study, we evaluated the relative contributions of CC and CM to winter wheat aboveground NPP (ANPP) in the 3HP and the relationships between climatic factors and ANPP using the first-order difference method from 2000 to 2020. RESULTS: CM had a greater influence on the ANPP of winter wheat than did CC. However, the relative contribution of CM to ANPP gradually decreased in humid and dry sub-humid regions with the development of winter wheat. Furthermore, in areas characterized by low temperatures and limited precipitation, CC became the dominant factor contributing to ANPP, indicating that varieties resilient to drought and cold should be selected in these regions. Minimum and average temperatures were the dominant factors driving spatiotemporal variations in ANPP during the early stage of winter wheat growth, whereas maximum temperature constrained growth throughout the winter wheat growth cycle. When winter wheat entered the vigorous growth stage, precipitation and solar radiation replaced temperature as the driving factors influencing winter wheat growth. CONCLUSION: The results of the present study provide guidance for optimizing winter wheat crop management in the 3HP. © 2023 Society of Chemical Industry.

Generation of sheep with defined FecBB and TBXT mutations and porcine blastocysts with KCNJ5G151R/+ mutation using prime editing.

BACKGROUND: Rewriting the genomes of living organisms has been a long-standing aim in the biological sciences. The revelation of the CRISPR/Cas9 technology has revolutionized the entire biological field. Since its emergence, this technology has been widely applied to induce gene knockouts, insertions, deletions, and base substitutions. However, the classical version of this system was imperfect for inducing or correcting desired mutations. A subsequent development generated more advanced classes, including cytosine and adenine base editors, which can be used to achieve single nucleotide substitutions. Nevertheless, these advanced systems still suffer from several limitations, such as the inability to edit loci without a suitable PAM sequence and to induce base transversions. On the other hand, the recently emerged prime editors (PEs) can achieve all possible single nucleotide substitutions as well as targeted insertions and deletions, which show promising potential to alter and correct the genomes of various organisms. Of note, the application of PE to edit livestock genomes has not been reported yet. RESULTS: In this study, using PE, we successfully generated sheep with two agriculturally significant mutations, including the fecundity-related FecBB p.Q249R and the tail length-related TBXT p.G112W. Additionally, we applied PE to generate porcine blastocysts with a biomedically relevant point mutation (KCNJ5 p.G151R) as a porcine model of human primary aldosteronism. CONCLUSIONS: Our study demonstrates the potential of the PE system to edit the genomes of large animals for the induction of economically desired mutations and for modeling human diseases. Although prime-edited sheep and porcine blastocysts could be generated, the editing frequencies are still unsatisfactory, highlighting the need for optimizations in the PE system for efficient generation of large animals with customized traits.

The survival of esophageal cancer by subtype in China with comparison to the United States.

Adenocarcinoma (AC) and squamous cell carcinoma (SCC) are the main subtypes of esophageal cancer (EC), but nationwide survival of both EC subtypes has never been reported in China. Our study aimed to estimate the survival trends of EC by subtype in China and compare them with those in the United States for the same period. We used data from 64 Chinese cancer registries, which included EC patients diagnosed during 2008 and 2015 and followed up until 31st December 2017. The 5-year age-standardized relative survival by subtype, sex, age group and urban or rural area between 2008 and 2017 were analyzed. We stratified survival estimates by calendar period (2008-2009, 2010-2011, 2012-2014 and 2015-2017). Data from the SEER 18 program were calculated to estimate the survival of EC in the United States. A further comparison between the survivals in areas covered and not covered by population-based endoscopic screening programs in China was conducted. A total of 129 962 records were included in the survival analyses. Results revealed that age-standardized 5-year relative survivals for AC and SCC increased in both China and the United States from 2008 to 2017. In 2015 to 2017, 5-year survival from both subtypes in China was better than the United States (SCC: 36.9% vs 18.5%, AC: 34.8% vs 22.3%). The survival for both subtypes was significantly higher in screening areas than in nonscreening areas in China (SCC: 40.6% vs 32.8%; AC: 43.0% vs 31.3%). A survival gap in EC by subtype exists between China and the United States. Our results may support the beneficial effect of population-based endoscopic screening for survival, and may be poised to inform national policy-making in both countries.

Genetically engineered chondrocytes overexpressing elastin improve cell retention and chondrogenesis in a three-dimensional GelMA culture system.

Elastic cartilage possesses many elastic fibers and has a high degree of elasticity. However, insufficient elastic fiber production remains unsolved in elastic cartilage tissue engineering. Exogenous elastin is difficult to degrade and violates cell proliferation and migration during cartilage regeneration. Moreover, exogenous elastic fibers are difficult to assemble with endogenous extracellular matrix components. We produced genetically engineered chondrocytes overexpressing elastin to boost endogenous elastic fiber production. After identifying that genetic manipulation hardly impacted the cell viability and chondrogenesis of chondrocytes, we co-cultured genetically engineered chondrocytes with untreated chondrocytes in a three-dimensional gelatin methacryloyl (GelMA) system. In vitro study showed that the co-culture system produced more elastic fibers and increased cell retention, resulting in strengthened mechanics than the control system with untreated chondrocytes. Moreover, in vivo implantation revealed that the co-culture GelMA system greatly resisted host tissue invasion by promoting elastic fiber production and cartilage tissue regeneration compared with the control system. In summary, our study indicated that genetically engineered chondrocytes overexpressing elastin are efficient and safe for promoting elastic fiber production and cartilage regeneration in elastic cartilage tissue engineering.

Crystal-Phase Engineering of Two-Dimensional Transition-Metal Dichalcogenides for Surface-Enhanced Raman Scattering: A Perspective.

Two-dimensional (2D) transition-metal dichalcogenides (TMDs) have emerged as promising materials for surface-enhanced Raman scattering (SERS) due to their unique electronic, optical, and mechanical properties. In this Perspective, we briefly introduce the fundamental properties, crystal-phase configurations, and phase transition strategies of TMDs materials. We then discuss the importance of the crystal phase in determining the SERS effect of TMDs, highlighting recent advances in phase-engineering approaches to affording remarkable SERS performance. By considering the current challenges and future directions for improving the crystal-phase engineering of TMDs in SERS, we also offer new insights into the design and synthesis of more promising TMD-based SERS substrates.

LINC00115 regulates lung adenocarcinoma progression via sponging miR-154-3p to modulate Sp3 expression.

The most commonly diagnosed and most lethal subtype of lung cancer is lung adenocarcinoma (LUAD). Therefore, more detailed understanding of the potential mechanism and identification of potential targets of lung adenocarcinoma is needed. A growing number of reports reveals that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression. In present study, we found that lncRNA LINC00115 was upregulated in LUAD tissues and cells. Functional studies revealed that LINC00115 knockdown inhibits the proliferation, growth, invasion, and migration of LUAD cells. Mechanically, we indicated that miR-154-3p is target microRNA of LINC00115, and the effect of downregulated LINC00115 on LUAD cells was partially reversed by the miR-154-3p antisense oligonucleotide (ASO-miR-154-3p). Further investigation revealed that Specificity protein 3 (Sp3) directly interacted with miR-154-3p, and the Sp3 level was positively correlated with the LINC00115 expression. Rescue experiments further showed that Sp3 overexpression partially restored the effect of downregulated LINC00115 on LUAD cells. Similarly, in vivo experiments confirmed that downregulated LINC00115 inhibited xenograft growth and Sp3 expression. Our results demonstrated that LINC00115 knockdown inhibited LUAD progression via sponging miR-154-3p to modulate Sp3 expression. These data indicate that the LINC00115/miR-154-3p/Sp3 axis can be a potential therapeutic target of LUAD.

Selenium mitigates the inhibitory effect of TBBPA on NETs release by regulating ROS/MAPK pathways-induced carp neutrophil apoptosis and necroptosis.

Tetrabromobisphenol A (TBBPA) is one of the most common and persistent organic pollutants found in the environment. When TBBPA is ingested by organisms through various pathways and stored in the body, it shows obvious harmful effects. Selenium (Se) works as an antioxidant in the body, allowing it to withstand the poisonous effects of dangerous substances. The effects and mechanisms of Se and TBBPA on carp neutrophil immune function, apoptosis, and necroptosis, however, are unknown. As a result, we created TBBPA exposure and Se antagonism models using carp neutrophils as study objects, and we investigated the expression of genes implicated in extracellular traps (NETs), cytokines, apoptosis, and necroptosis. The findings demonstrated that extracellular traps neutrophils in the TBBPA group displayed the inhibition of NETs, apoptosis, and necrosis, as well as an increase in Reactive oxygen species (ROS) levels and activation of the MAPK pathway. The expression of genes related to the mitochondrial apoptosis pathway (Bax, Cyt-c, Bcl-2 and Caspase-3) and necroptosis pathway (MLKL, RIPK1, RIPK3, Caspase-8 and FADD) were activated. The expression of inflammatory factors IL-1 and TNF-α were increased, and the expression of IL-2 and IFN-γ were decreased. But an appropriate concentration of Se can mitigate the effects of TBBPA. Our results suggest that Se can mitigate the inhibitory effect of TBBPA on NETs release by regulating apoptosis and necroptosis of carp neutrophil via ROS/MAPK pathways. These results provide a basis information for exploring the toxicity of TBBPA, and enrich the anti-toxicity mechanism of trace element Se in the body.

Apparent activity and specific activity of lanthanides (La, Ce, Nd) decorated Co-MOF derivatives for electrocatalytic water splitting.

Lanthanide (Ln) rare Earth (RE) elements are often used to incorporate and regulate the local coordination environment and electronic configuration of transition metal based electrocatalysts for acquiring improved electrocatalytic performance. But for a given pristine electrode, is a Ln element concentrated more on promoting the apparent activity of original electrode or on enhancing its specific activity? To address this issue, Ln (La, Ce and Nd) decorated ZIF-67 derivative electrodes (Ln/Co/NC) were fabricated following with the detailed experimental testing of apparent activity and specific activity of assembled electrodes. X-ray photoelectron spectroscopy data confirmed that Ce, Nd and La have played their own role in regulating the coordination electronic structure of the surface atoms of the derived Co/NC by forming different types of chemical bonds. Electrochemical (EC) results confirmed that Ce is concentrated more on the apparent activity of derived Co/NC electrode with the smallest overpotential at 50 mA cm-2(η50), while Nd contributes more to its reaction kinetic property with the smallest value of Tafel slope in alkaline hydrogen evolution reaction process. But for oxygen evolution reaction, all of La, Ce and Nd deteriorate the apparent activity of the pristine Co/NC electrode. Comparatively, La shows a greater ability to modulate the specific activity of Co/NC with a larger electrochemical active surface area normalized current density, while Nd exhibits the best ability to re-establish the properties of reaction centers. This work illustrates the difference influence of La, Ce and Nd on the apparent activity and specific activity of the ZIF-67 derivative Co/NC electrode. It will do some favors in engineering RE elements modified composite electrodes for EC applications.

The occurence of cancer in ageing populations at global and regional levels, 1990 to 2019.

BACKGROUND: population ageing contributes to increased cancer cases and deaths and has profound implications for global healthcare systems. We estimated the trends of cancer cases and deaths in ageing populations at global and regional levels. METHODS: using data from the Global Burden of Disease Study 2019, we analysed the change in cancer cases and deaths associated with population ageing, population growth and epidemiological factors from 1990 to 2019 using decomposition analysis. Additionally, we estimated the proportions of people aged 65 years and over accounting for total cases and deaths, and investigated relationships between the proportions and the Sociodemographic Index (SDI) using the Pearson correlation coefficient. RESULTS: from 1990 to 2019, there was an increase of 128.9% for total cases and 74.8% for total deaths in all cancers combined; the percentages of older people increased from 48.6% to 56.4% for cases and from 52.0% to 61.9% for deaths. Population ageing contributed to the largest increase in global cancer occurrence, with 56.5% for cases and 63.3% for deaths. However, the changes attributed to epidemiological factors was 5.2% for cancer cases and -33.4% for cancer deaths. The proportions of total cases and deaths of older adults were positively correlated with socioeconomic development of the country. CONCLUSION: our findings revealed that the main contributor to increased cancer cases and deaths has changed from comprehensive epidemiological factors to demographic shifts. To respond to the rapidly growing occurrence of cancer in ageing populations, the global health priority should focus on meeting the rising demand for cancer diagnosis, treatment and care services for older people.

The effect of a-Lipoic acid (ALA) on oxidative stress, inflammation, and apoptosis in high glucose-induced human corneal epithelial cells.

PURPOSE: Oxidative stress and inflammation had been proved to play important role in the progression of diabetic keratopathy (DK). The excessive accumulation of AGEs and their bond to AGE receptor (RAGE) in corneas that cause the formation of oxygen radicals and the release of inflammatory cytokines, induce cell apoptosis. Our current study was aimed to evaluate the effect of ALA on AGEs accumulation as well as to study the molecular mechanism of ALA against AGE-RAGE axis mediated oxidative stress, apoptosis, and inflammation in HG-induced HCECs, so as to provide cytological basis for the treatment of DK. METHODS: HCECs were cultured in a variety concentration of glucose medium (5.5, 10, 25, 30, 40, and 50 mM) for 48 h. The cell proliferation was evaluated by CCK-8 assay. Apoptosis was investigated with the Annexin V- fluorescein isothiocyanate (V-FITC)/PI kit, while, the apoptotic cells were determined by flow cytometer and TUNEL cells apoptosis Kit. According to the results of cell proliferation and cell apoptosis, 25 mM glucose medium was used in the following HG experiment. The effect of ALA on HG-induced HCECs was evaluated. The HCECs were treated with 5.5 mM glucose (normal glucose group, NG group), 5.5 mM glucose + 22.5 mM mannitol (osmotic pressure control group, OP group), 25 mM glucose (high glucose group, HG group) and 25 mM glucose + ALA (HG + ALA group) for 24 and 48 h. The accumulation of intracellular AGEs was detected by ELISA kit. The RAGE, catalase (CAT), superoxide dismutase 2 (SOD2), cleaved cysteine-aspartic acid protease-3 (Cleaved caspase-3), Toll-like receptors 4 (TLR4), Nod-like receptor protein 3 (NLRP3) inflammasome, interleukin 1 beta (IL-1 ß), and interleukin 18 (IL-18) were quantified by RT-PCR, Western blotting, and Immunofluorescence, respectively. Reactive oxygen species (ROS) production was evaluated by fluorescence microscope and fluorescence microplate reader. RESULTS: When the glucose medium was higher than 25 mM, cell proliferation was significantly inhibited and apoptosis ratio was increased (P < 0.001). In HG environment, ALA treatment alleviated the inhibition of HCECs in a dose-dependent manner, 25 µM ALA was the minimum effective dose. ALA could significantly reduce the intracellular accumulation of AGEs (P < 0.001), activate protein and genes expression of CAT and SOD2 (P < 0.001), and therefore inhibited ROS-induced oxidative stress and cells apoptosis. Besides, ALA could effectively down-regulate the protein and gene level of RAGE, TLR4, NLRP3, IL-1B, IL-18 (P < 0.05), and therefore alleviated AGEs-RAGE-TLR4-NLRP3 pathway-induced inflammation in HG-induced HCECs. CONCLUSION: Our study indicated that ALA could be a desired treatment for DK due to its potential capacity of reducing accumulation of advanced glycation end products (AGEs) and down-regulating AGE-RAGE axis-mediated oxidative stress, cell apoptosis, and inflammation in high glucose (HG)-induced human corneal epithelial cells (HCECs), which may provide cytological basis for therapeutic targets that are ultimately of clinical benefit.

Optimized Cas9:sgRNA delivery efficiently generates biallelic MSTN knockout sheep without affecting meat quality.

BACKGROUND: CRISPR/Cas9-based genome-editing systems have been used to efficiently engineer livestock species with precise genetic alterations intended for biomedical and agricultural applications. Previously, we have successfully generated gene-edited sheep and goats via one-cell-stage embryonic microinjection of a Cas9 mRNA and single-guide RNAs (sgRNAs) mixture. However, most gene-edited animals produced using this approach were heterozygotes. Additionally, non-homozygous gene-editing outcomes may not fully generate the desired phenotype in an efficient manner. RESULTS: We report the optimization of a Cas9 mRNA-sgRNA delivery system to efficiently generate homozygous myostatin (MSTN) knockout sheep for improved growth and meat production. Firstly, an sgRNA selection software (sgRNAcas9) was used to preliminarily screen for highly efficient sgRNAs. Ten sgRNAs targeting the MSTN gene were selected and validated in vitro using sheep fibroblast cells. Four out of ten sgRNAs (two in exon 1 and two in exon 2) showed a targeting efficiency > 50%. To determine the optimal CRISPR/Cas9 microinjection concentration, four levels of Cas9 mRNA and three levels of sgRNAs in mixtures were injected into sheep embryos. Microinjection of 100 ng/µL Cas9 mRNA and 200 ng/µL sgRNAs resulted in the most improved targeting efficiency. Additionally, using both the highly efficient sgRNAs and the optimal microinjection concentration, MSTN-knockout sheep were generated with approximately 50% targeting efficiency, reaching a homozygous knockout efficiency of 25%. Growth rate and meat quality of MSTN-edited lambs were also investigated. MSTN-knockout lambs exhibited increased body weight and average daily gain. Moreover, pH, drip loss, intramuscular fat, crude protein, and shear force of gluteal muscles of MSTN-knockout lambs did not show changes compared to the wild-type lambs. CONCLUSIONS: This study highlights the importance of in vitro evaluation for the optimization of sgRNAs and microinjection dosage of gene editing reagents. This approach enabled efficient engineering of homozygous knockout sheep. Additionally, this study confirms that MSTN-knockout lambs does not negatively impact meat quality, thus supporting the adoption of gene editing as tool to improve productivity of farm animals.

Global and national trends in the age-specific sex ratio of esophageal cancer and gastric cancer by subtype.

A male predominance was observed in esophageal and gastric cancers, though present limited data has revealed variations by age. We aim to investigate the global age-specific sex differences in esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cardia cancer (GCC) and gastric noncardia cancer (GNCC). Data on esophageal and gastric cancers incidence by diagnosis year, sex, histology, subsite and age group were extracted from 171 registries in 54 countries included in the last two volumes (X and XI, 2003-2012) of Cancer Incidence in Five Continents, which contributing to over 80% of the global burdens of these cancers. Age-standardized incidence rates (ASIRs) and male-to-female ASIRs ratios were estimated for esophageal and gastric cancers, by histological subtype and subsite, globally and by country. We consistently observed a male predominance in esophageal and gastric cancers across the world from 2003 to 2012, with male-to-female ASIRs ratios of 6.7:1 for EAC, 3.3:1 for ESCC, 4.0:1 for GCC and 2.1:1 for GNCC. The sex differences were consistent across time periods but varied significantly by age across the life span. Across the four cancer types, the male-to-female incidence rate ratios increased from young ages, approaching a peak at ages 60-64, but sharply declined thereafter. Similar "low-high-low" trends of age-specific sex ratio were observed in other digestive cancers including liver, pancreas, colon and rectum with peak ages ranging from 50 to 65. Age-dependent risk factors warrant further investigation to aid our understanding of the underlying etiologies of esophageal and gastric cancers by histological subtype and subsite.

A dual-signal electrochemical immunosensor for the detection of HPV16 E6 oncoprotein based on PdBP dendritic ternary nanospheres and MBSi-Chi nanocomposites.

Cervical cancer is a common cancer in women. HPV16 E6 oncoprotein is a reliable biomarker for cervical cancer. Although there are other methods for detecting E6 oncoprotein, the electrochemical method has more advantages, such as low cost, convenience and speed. In this study, a novel dual-signal electrochemical immunosensor for quick and sensitive detection of E6 oncoprotein based on a high efficiency catalyst and signal label was developed. Herein, to achieve quick detection, palladium-boron-phosphorus dendritic ternary nanospheres (PdBP NSs) not only acted as a catalyst to catalyze H2O2, but also as a support material to capture antibodies. Moreover, to realize sensitive detection, nanocomposites of mesoporous silica nanoparticles loaded with methylene blue and coated with chitosan (MBSi-Chi) were synthesized as a signal label, which can produce electrochemical signal. Under optimal conditions, the label-free immunosensor exhibited a linear range of 100 fg mL-1 to 4 ng mL-1 with a detection limit of 72.8 fg mL-1 (S/N = 3), and the sandwich-type immunosensor presented a linear range of 50 fg mL-1 to 4 ng mL-1 with a detection limit of 34.1 fg mL-1 (S/N = 3). The as-prepared dual-signal immunosensor had desirable specificity, stability and repeatability, implying its potential applications in clinical laboratory.

A network meta-analysis of the effectiveness and safety of drugs for restless legs syndrome in dialysis patients.

OBJECTIVE: To evaluate the efficacy and safety of nine pharmacological interventions for restless legs syndrome (RLS) in dialysis patients. METHODS: An electronic database was used to retrieve eligible trials from PubMed, Cochrane, Embase, and Web of Science. Stata 14.2 software was used to perform network meta-analysis. The primary measure was the RLS score, and the secondary measure was used to evaluate the side effects of the drug. The surface under the cumulative ranking curve method was used to rank the merits of intervention measures. A comparison of the two interventions is shown on a league table. RESULTS: Finally, nine randomized controlled trials (RCTs) with a total of 377 participants were included. From the results of the network meta-analysis, all treatments ranked higher than placebo in terms of improving clinical symptoms, but only vitamin C (standardized mean difference [SMD] = -1.47 95% confidence interval [CI] -2.89, -0.05) showed significant differences compared with placebo. In terms of safety, there were no serious adverse reactions to any of the treatments compared to placebo. CONCLUSION: Currently, existing evidence suggests that vitamin C may be the most ideal drug to improve the symptoms of RLS in dialysis patients.

The antagonistic effect of melatonin on TBBPA-induced apoptosis and necroptosis via PTEN/PI3K/AKT signaling pathway in swine testis cells.

Tetrabromobisphenol A (TBBPA) is a widely used industrial brominated flame retardant, which can endanger animal and human health, including cytotoxicity, endocrine disruption, reproductive toxicity and so on. Melatonin (MT) is a noteworthy free radical scavenger and an antioxidant to alleviate oxidative stress. To investigate the cytotoxic of TBBPA on swine testis cells (ST cells), as well as the antagonistic effect of MT, we established TBBPA exposure and MT antagonistic models, used flow cytometry and AO/EB staining methods to detect apoptosis and necroptosis, used DCFH-DA method to examine the content of reactive oxygen species (ROS) and investigated the expression of associated genes using RT-PCR and Western blot. According to our findings, TBBPA exposure induced cell death in ST cells. TBBPA increased ROS levels, thus increasing PTEN expression and decreasing PI3K and AKT expression. Apoptosis-related factors (Caspase-3, Bax, Cyt-c, and Caspase-9) and necroptosis-related factors (RIPK1, RIPK3, and MLKL) were considerably elevated, in addition to the reduced expression of BCL-2 and Caspase-8. We also found that MT inhibited apoptosis and necroptosis in TBBPA-induced ST cells and effectively resolved the abnormal expression of related signaling pathways. In summary, the above results indicate that MT alleviates the disorder of PTEN/PI3K/AKT signaling pathway via inhibiting ROS overproduction, thereby mitigating apoptosis and necroptosis caused by TBBPA. This research provides a theoretical basis for further understanding of the toxicity of TBBPA and the detoxification of MT against environmental toxics.

Polystyrene microplastics induce apoptosis and necroptosis in swine testis cells via ROS/MAPK/HIF1α pathway.

Microplastics (MPs) generally refer to the plastic fragments or particles smaller than 5 mm in diameter, which are closely concerned due to their widespread presence in the environment. Recent studies have shown that MPs have a serious threat on the reproductive health of organisms. Pigs are often selected as the model animals because of their high similarity to human tissues and organs. However, there are no reports on the effects and mechanisms of MPs exposure on swine germ cells. In the present study, we established swine testis (ST) cell models exposed to 250, 500, and 1000 µg/ml polystyrene microplastics (PS-MPs, 1-10 µm), respectively. The findings revealed that PS-MPs reduced cell viability dose-dependently. Acridine orange/ethidium bromide staining and flow cytometry results indicated the occurrence of apoptosis and necrosis in ST cells under PS-MPs exposure, and the expression changes of relevant marker genes (B-cell lymphoma-2, Bcl-2 Associated X, Caspase-3, Caspase-9, Receptor-interacting protein kinase 1, Receptor-interacting protein kinase 3, Mixed lineage kinase domain-like, and Caspase-8) were clarified via quantitative real-time PCR and western blot. Further mechanistic studies found that PS-MPs treatment induced excessive intracellular reactive oxygen species (ROS) production, which promoted the phosphorylation of mitogen-activated protein kinase (MAPK) pathway-related genes (P38, c-Jun N-terminal kinase, extracellular regulated protein kinases) and activated the downstream gene hypoxia-inducible factor (HIF1α). In conclusion, our study suggests that PS-MPs treatment causes apoptosis and necroptosis in ST cells via ROS/MAPK/HIF1α signaling pathway.

Intergenerational Transmission of Depressive Symptoms from Mothers to Adolescents: A Moderated Mediation Model.

Substantial literature investigating the intergenerational transmission of depressive symptoms has primarily focused on mothers and adolescents, whereas less is known about the potential role of fathers, especially their parenting behaviors. This study aimed to address this gap by examining the mediating role of maternal parenting, and the moderating role of paternal parenting in this intergenerational transmission pathway. A total of 528 Chinese community adolescents (Mage = 12.70 ± 1.49 years; 48.7%, girls) and their mothers participated. After adolescent sex, age, maternal educational levels, and monthly household income were controlled for, both maternal warmth and rejection mediated the association between maternal and adolescent depressive symptoms. More importantly, paternal warmth buffered the adverse effect of maternal depressive symptoms and maternal rejection on adolescent depressive symptoms. These findings highlight the buffering role of paternal parenting in blocking the intergenerational transmission risk of depressive symptoms from mothers to adolescents and emphasize the need for father-focused interventions.