Boolean Computation in Single-Transistor Neuron.

Brain neurons exhibit far more sophisticated and powerful information-processing capabilities than the simple integrators commonly modeled in neuromorphic computing. A biological neuron can in fact efficiently perform Boolean algebra, including linear nonseparable operations. Traditional logic circuits require more than a dozen transistors combined as NOT, AND, and OR gates to implement XOR. Lacking biological competency, artificial neural networks require multilayered solutions to exercise XOR operation. Here, it is shown that a single-transistor neuron, harnessing the intrinsic ambipolarity of graphene and ionic filamentary dynamics, can enable in situ reconfigurable multiple Boolean operations from linear separable to linear nonseparable in an ultra-compact design. By leveraging the spatiotemporal integration of inputs, bio-realistic spiking-dependent Boolean computation is fully realized, rivaling the efficiency of a human brain. Furthermore, a soft-XOR-based neural network via algorithm-hardware co-design, showcasing substantial performance improvement, is demonstrated. These results demonstrate how the artificial neuron, in the ultra-compact form of a single transistor, may function as a powerful platform for Boolean operations. These findings are anticipated to be a starting point for implementing more sophisticated computations at the individual transistor neuron level, leading to super-scalable neural networks for resource-efficient brain-inspired information processing.

Preconception mitochondrial DNA copy number plays a crucial role in linking prenatal air pollution with the risk of preterm birth.

The relationship between maternal peripheral blood mitochondrial DNA and adverse pregnancy outcomes, specifically preterm birth (PTB), remains uncertain. To investigate the effects of preconception mitochondrial DNA copy number (mtDNAcn) on the association between prenatal air pollutants exposure and PTB risk, a total of 1871 expectant mothers from six regions in Henan Province were recruited. Information regarding air pollutants was obtained from 151 environmental monitoring sites, and relative mtDNAcn was evaluated using real-time PCR analysis. After adjusting for potential confounding variables, it was determined that the risk of PTB increased with elevated levels of inhalable particulate matter (PM10), fine particulate matter (PM2.5), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3) exposure (P < 0.05) but decreased with higher nitrogen dioxide (NO2) exposure (0.05 < P < 0.10) during the entire pregnancy. Additionally, the preconception relative mtDNAcn was lower in the PTB group (0.82 ± 0.23) compared to the term group (0.92 ± 0.29). Furthermore, for each 0.1-unit increase in preconception mtDNAcn, the risk of PTB decreased by 14.8%. Stratified analyses revealed that the risk of PTB rose with increasing O3 concentrations, regardless of the relative mtDNAcn. Moreover, the study found a significant association between PTB risk and prenatal exposure to elevated PM10, PM2.5, SO2, and CO, particularly in mothers with low mtDNAcn (≤0.88) (P < 0.05). Conversely, a decrease in the PTB risk was observed with elevated NO2 exposure in mothers with high mtDNAcn (>0.88). Interaction analysis revealed that exposure to PM10, PM2.5, SO2, NO2, and CO interacted with mtDNAcn, respectively, affecting PTB risk (P-interaction<0.05). These findings indicate a noteworthy association between PTB risk and prenatal air pollutants exposure, which is influenced by the preconception mtDNAcn.

Design, synthesis, and antifungal activity of novel pyrazole carboxamide derivatives containing benzimidazole moiety as potential SDH inhibitors.

To address the urgent need for new antifungal agents, a collection of novel pyrazole carboxamide derivatives incorporating a benzimidazole group were innovatively designed, synthesized, and evaluated for their efficacy against fungal pathogens. The bioassay results revealed that the EC50 values for the compounds A7 (3-(difluoromethyl)-1-methyl-N-(1-propyl-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxamide) and B11 (N-(1-(4-chlorobenzyl)-1H-benzo[d]imidazol-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide) against B. cinerea were notably low to 0.79 µg/mL and 0.56 µg/mL, respectively, demonstrating the potency comparable to that of the control fungicide boscalid, which has an EC50 value of 0.60 µg/mL. Noteworthy is the fact that in vivo tests demonstrated that A7 and B11 showed superior protective effects on tomatoes and strawberries against B. cinerea infection when juxtaposed with the commercial fungicide carbendazim. The examination through scanning electron microscopy revealed that B11 notably alters the morphology of the fungal mycelium, inducing shrinkage and roughening of the hyphal surfaces. To elucidate the mechanism of action, the study on molecular docking and molecular dynamics simulations was conducted, which suggested that B11 effectively interacts with crucial amino acid residues within the active site of succinate dehydrogenase (SDH). This investigation contributes a novel perspective for the structural design and diversification of potential SDH inhibitors, offering a promising avenue for the development of antifungal therapeutics.

All-2D-Materials Subthreshold-Free Field-Effect Transistor with Near-Ideal Switching Slope.

The Boltzmann Tyranny, set by thermionic statistics, dictates the lower limit of switching slope (SS) of a MOSFET to be 60 mV/dec, the fundamental barrier for low-dissipative electronics. The large SS leads to nonscalable voltage, significant leakage, and power consumption, particularly at short channels, making transistor scaling an intimidating challenge. In recent decades, an array of steep-slope transistors has been proposed; none is close to an ideal switch with ultimately abrupt switching (SS ∼ 0 mV/dec) between the binary logic states. We demonstrated an all-2D-materials van-der-Waals-heterostructure (vdW)-based FET that exhibits ultrasteep switching (0.33 mV/dec), a large on/off current ratio (∼107), and an ultralow off current (∼0.1 pA). The "Subthreshold-Free" operation achieved by the collective behavior of functional materials enables FET switching directly from the OFF-state to the ON-state with entirely eliminated subthreshold region, behaving as the ideal logic switch. Two-inch wafer-scale device fabrication is demonstrated. Boosted by device innovation and emerging materials, the research presents an advancement in achieving the "beyond-Boltzmann" transistors, overcoming one of the CMOS electronics' most infamous technology barriers that have plagued the research community for decades.

High expression of YEATS2 as a predictive factor of poor prognosis in patients with hepatocellular carcinoma.

YEATS domain containing 2 (YEATS2), it may function as a proto-oncogene. This study aims to investigate if YEATS2 correlates with prognosis in hepatocellular carcinoma. The prognostic landscape of YEATS2 and its relationship with expression in hepatocellular carcinoma were deciphered with public databases, RT-qPCR and western-blot in tissue samples. The expression profiling and prognostic value of YEATS2 were explored using UALCAN, TIMER, OncoLnc database. Transcription and survival analyses of YEATS2 in hepatocellular carcinoma were investigated with cBioPortal database. The STRING database was explored to identify molecular functions and signaling pathways downstream of YEATS2. YEATS2 expression was significantly higher in hepatocellular carcinoma compared with adjacent non-malignant tissues. Promoter methylation of YEATS2 exhibited different patterns in hepatocellular carcinoma. High expression of YEATS2 was associated with poorer survival. Mechanistically, YEATS2 was involved in mediating multiple biological processes including morphogenesis and migration.

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors.

The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 µg/mL that was superior to that of the agricultural fungicide boscalid (2.2 µg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 µM that was superior to that of boscalid (7.9 µM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.

A Coupled Statistical and Deterministic Model for Forecasting Climate-Driven Dengue Incidence in Selangor, Malaysia.

The mosquito-borne dengue virus remains a major public health concern in Malaysia. Despite various control efforts and measures introduced by the Malaysian Government to combat dengue, the increasing trend of dengue cases persists and shows no sign of decreasing. Currently, early detection and vector control are the main methods employed to curb dengue outbreaks. In this study, a coupled model consisting of the statistical ARIMAX model and the deterministic SI-SIR model was developed and validated using the weekly reported dengue data from year 2014 to 2019 for Selangor, Malaysia. Previous studies have shown that climate variables, especially temperature, humidity, and precipitation, were able to influence dengue incidence and transmission dynamics through their effect on the vector. In this coupled model, climate is linked to dengue disease through mosquito biting rate, allowing real-time forecast of dengue cases using climate variables, namely temperature, rainfall and humidity. For the period chosen for model validation, the coupled model can forecast 1-2 weeks in advance with an average error of less than 6%, three weeks in advance with an average error of 7.06% and four weeks in advance with an average error of 8.01%. Further model simulation analysis suggests that the coupled model generally provides better forecast than the stand-alone ARIMAX model, especially at the onset of the outbreak. Moreover, the coupled model is more robust in the sense that it can be further adapted for investigating the effectiveness of various dengue mitigation measures subject to the changing climate.

Mouse auditory cortex sub-fields receive neuronal projections from MGB subdivisions independently.

Mouse auditory cortex is composed of six sub-fields: primary auditory field (AI), secondary auditory field (AII), anterior auditory field (AAF), insular auditory field (IAF), ultrasonic field (UF) and dorsoposterior field (DP). Previous studies have examined thalamo-cortical connections in the mice auditory system and learned that AI, AAF, and IAF receive inputs from the ventral division of the medial geniculate body (MGB). However, the functional and thalamo-cortical connections between nonprimary auditory cortex (AII, UF, and DP) is unclear. In this study, we examined the locations of neurons projecting to these three cortical sub-fields in the MGB, and addressed the question whether these cortical sub-fields receive inputs from different subsets of MGB neurons or common. To examine the distributions of projecting neurons in the MGB, retrograde tracers were injected into the AII, UF, DP, after identifying these areas by the method of Optical Imaging. Our results indicated that neuron cells which in ventral part of dorsal MGB (MGd) and that of ventral MGB (MGv) projecting to UF and AII with less overlap. And DP only received neuron projecting from MGd. Interestingly, these three cortical areas received input from distinct part of MGd and MGv in an independent manner. Based on our foundings these three auditory cortical sub-fields in mice may independently process auditory information.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.

Enhanced photocatalytic reduction of Cr(VI) from aqueous solution using Fe0/TiO2-based polymeric nanocomposites.

The combination of zerovalent iron (Fe0) and titanium dioxide (TiO2) has been investigated as a promising method for environmental remediation. However, it is a challenge to prepare conveniently desirable Fe0/TiO2 nanocomposites with excellent efficiency and reusability. Here, a novel nanocomposite material, Fe0/TiO2@D201, was synthesized to enhance the removal of Cr(VI) from an aqueous system by impregnating Fe0 and TiO2 inside a commercial anion exchanger (D201). The proposed structure and Cr(VI) removal mechanism of Fe0/TiO2@D201 were confirmed using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis. Compared to the monometallic samples (Fe0-D201 and TiO2-D201), Fe0/TiO2@D201 showed outstanding Cr(VI) removal and the removal ratio reached up to 97.30% after 120 min of UV light irradiation. The removal of Cr(VI) by Fe0/TiO2@D201 remained high (91.70%) even after four cycles, indicating the stability of the nanocomposites toward Cr(VI) removal and their strong potential for practical applications. The addition of ethylenediaminetetraacetic acid (EDTA) positively affected the Cr(VI) reduction process, whereas the addition of Na2S2O8 negatively affected the Cr(VI) process. The XPS results revealed that the photocatalytic reduction of Cr(VI) by Fe0/TiO2@D201 involved the capture of photoexcited electrons and Fe0 reduction. A path for the photogenerated electrons engaging in the reduction reaction to improve the utilization of Fe0 was proposed. These results demonstrate that Fe0/TiO2@D201 is a promising alternative composite catalyst for the efficient Cr(VI) removal from contaminated water.

A pilot clinical study of developing an External Assist Targeting Device for rapid and precise renal calyx access during percutaneous nephrolithotomy.

Objective: To design a device to increase the accuracy of the targeting process and reduce the radiation exposure to both the patients and the medical staff. Methods: We analyzed the inherent problem and designed the External Assist Targeting Device (EATD) to assist in the alignment of needle targeting on the desired renal calyx under fluoroscopic guidance. The EATD was designed to allow rapid and precise access to calyces at all angles, with a simple two-step puncture protocol developed for puncturing a target renal calyx. We then tested the device in a pilot human trial with four patients. Results: In experiments with phantom models, the time for successful targeting was reduced by 31% using the device. The mean fluoroscopic time was reduced by 40%. In initial human trial, the puncture time was shortened by 66% and the radiation dose was decreased by 65% compared to free-hand technique. No complication was observed during the trial. Conclusion: The EATD was found to be cost effective, portable, simple to set up, and safe to operate for assisting in the percutaneous nephrolithotomy procedures. Our preliminary tests showed high degree of accuracy in gaining precise access to a targeted renal calyx with much shorter time and lesser radiation dose. The EATD also has the potential to be used to access other organs with precision under fluoroscopic guidance.

Potential Succinate Dehydrogenase Inhibitors Bearing a Novel Pyrazole-4-sulfonohydrazide Scaffold: Molecular Design, Antifungal Evaluation, and Action Mechanism.

Aiming to develop novel antifungal agents with a distinctive molecular scaffold targeting succinate dehydrogenase (SDH), 24 N'-phenyl-1H-pyrazole-4-sulfonohydrazide derivatives were first devised, synthesized, and verified by 1H NMR, 13C NMR, high-resolution mass spectrometry (HRMS), and single-crystal X-ray diffraction analysis. The bioassays revealed that the target compounds possessed highly efficient and broad-spectrum antifungal activities against four tested plant pathogenic fungi Rhizoctonia solani (R. solani), Botrytis cinerea, Fusarium graminearum, and Alternaria sonali. Strikingly, compound B6 was assessed as the selective inhibitor against R. solani, with an in vitro EC50 value (0.23 µg/mL) that was similar to that of thifluzamide (0.20 µg/mL). The in vivo preventative effect of compound B6 (75.76%) at 200 µg/mL against R. solani was roughly comparable to thifluzamide (84.31%) under the same conditions. The exploration of morphological observations indicated that compound B6 could strongly damage the mycelium morphology, obviously increase the permeability of the cell membrane, and dramatically increase the number of mitochondria. Compound B6 also significantly inhibited SDH enzyme activity with an IC50 value of 0.28 µg/mL, and its fluorescence quenching dynamic curves were similar to that of thifluzamide. Molecular docking and molecular dynamics simulations demonstrated that compound B6 could strongly interact with similar residues around the SDH active pocket as thifluzamide. The present study revealed that the novel N'-phenyl-1H-pyrazole pyrazole-4-sulfonohydrazide derivatives are worthy of being further investigated as the promising replacements of traditional carboxamide derivatives targeting SDH of fungi.

Identification of key immune genes related to lymphatic metastasis of papillary thyroid cancer via bioinformatics analysis and experimental validation.

Objective: The current research aimed to development and validation in signature immune genes for lymphatic metastasis in papillary thyroid cancer (PTC). Method: Weighted correlation network analysis (WGCNA) was performed to identify genes closely correlated with lymphatic metastasis in PTC from TCGA database. Information on immune-related genes (IRGs) was obtained from the ImmPort database. Crossover genes were used with the R package clusterProfiler for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Key genes in the protein-protein interaction network of cross-targets were obtained using Cytoscape. Lasso and Random Forest (RF) models were utilized to identify pivotal genes. We constructed a nomogram based on the hub genes. The correlation between hub genes and immune cell infiltration was explored. We collected and assessed clinical samples via immunohistochemistry to detect the expression of hub genes. Result: In total, 122 IRGs were correlated with lymphatic metastases from PTC. There are 10 key IRGs in the protein-protein interaction network. Then, three hub genes including PTGS2, MET, and ICAM1 were established using the LASSO and RF models. The expression of these hub genes was upregulated in samples collected from patients with lymphatic metastases. The average area under the curve of the model reached 0.83 after a 10-fold and 200-time cross-validation, which had a good prediction ability. Immuno-infiltration analysis showed that the three hub genes were significantly positively correlated with resting dendritic cells and were negatively correlated with activated natural cells, monocytes, and eosinophils. Immunohistochemistry results revealed that lymph node metastasis samples had a higher expression of the three hub genes than non-metastasis samples. Conclusion: Via bioinformatics analysis and experimental validation, MET and ICAM1 were found to be upregulated in lymph node metastasis from papillary thyroid carcinoma. Further, the two hub genes were closely correlated with activated natural killer cells, monocytes, resting dendritic cells, and eosinophils. Therefore, these two genes may be novel molecular biomarkers and therapeutic targets in lymph node metastasis from papillary thyroid carcinoma.

Carrier Modulation in 2D Transistors by Inserting Interfacial Dielectric Layer for Area-Efficient Computation.

2D materials with atomic thickness display strong gate controllability and emerge as promising materials to build area-efficient electronic circuits. However, achieving the effective and nondestructive modulation of carrier density/type in 2D materials is still challenging because the introduction of dopants will greatly degrade the carrier transport via Coulomb scattering. Here, a strategy to control the polarity of tungsten diselenide (WSe2 ) field-effect transistors (FETs) via introducing hexagonal boron nitride (h-BN) as the interfacial dielectric layer is devised. By modulating the h-BN thickness, the carrier type of WSe2 FETs has been switched from hole to electron. The ultrathin body of WSe2 , combined with the effective polarity control, together contribute to the versatile single-transistor logic gates, including NOR, AND, and XNOR gates, and the operation of only two transistors as a half adder in logic circuits. Compared with the use of 12 transistors based on static Si CMOS technology, the transistor number of the half adder is reduced by 83.3%. The unique carrier modulation approach has general applicability toward 2D logic gates and circuits for the improvement of area efficiency in logic computation.

High expression of caspase-8 as a predictive factor of poor prognosis in patients with esophageal cancer.

BACKGROUND: Esophageal carcinoma (ESCA) is considered to be one of the most common gastrointestinal cancers. Caspase-8 (CASP8) is a key protein of cross-talk signaling in a variety of cancers. However, the role of CASP8 expression in the prognosis of patients with ESCA has remained unexplored. Hence, it is needed to explore the clinical significance of CASP8 expression in ESCA. METHODS: The expression and prognosis of CASP8 were investigated in ESCA using the UALCAN, GEDS, TIMER, and OncoLnc databases. The CASP8 genetic variations in ESCA were assessed using the cBioPortal database. The correlation between CASP8 expression and tumor immune invasion and immune cell surface indicators was examined using the TIMER and TISIDTISIDB datasets. Meanwhile, the abundance of the immunological cells in the tumor and healthy tissues was assessed by the CIBERSORT method. Next, information on the co-expressed genes of the differentially expressed genes (DEGs) in ESCA-tumor and ESCA-healthy tissues was obtained using the cBioPortal, UALCAN, and Coexpedia databases. Subsequently, the PPI network was constructed and the GO and KEGG pathways were analyzed using the SIRING database. Finally, CASP8 mRNA and protein expression in the ESCA tissues and matched adjacent healthy tissues were analyzed using qRT-PCR, immune-blotting, and immunohistochemistry. Additionally, the relationship between clinicopathological features and CASP8 expression was assessed. RESULTS: ESCA tissues had higher levels of CASP8 mRNA and protein expression compared to healthy tissues. patients with an elevated level of CASP8 expression had poor overall survival (OS). CASP8 expression was significantly correlated with the degree of differentiation (P = 0.004) and lymph node metastasis (P = 0.044). There were diverse patterns of association between immunological cell surface biomarkers and CASP8 expression. CONCLUSION: ESCA showed significant levels of CASP8 expression which may serve as a prognostic biomarker correlated to immune infiltrates in ESCA.

Spatiotemporal Patterns of Adverse Pregnancy Outcomes in Rural Areas of Henan, China.

The spatial patterns of adverse pregnancy outcomes (APOs) are complex, vary by place, and remain not entirely clear. This study investigated spatiotemporal patterns of APOs in rural areas of Henan, China. We used data from 1,315,327 singleton pregnancies during 2013-2016 in rural areas of Henan, China, from the National Free Pre-pregnancy Checkup Program (NFPCP). A spatiotemporal analysis of APOs was conducted based on the time of conception and current address. Results of seasonality decomposed showed a slight decline in the incidence rate of APOs (12.93% to 11.27% in the compound trend) among the participants from 2013 to 2016 and also variation in annual periodicity (peaking in autumn at 12.66% and hitting bottom in spring at 11.16%). Spatial clusters of APOs were concentrated in an intersection band of northwestern to southeastern Henan Province (with a relative risk ratio ranging from 3.66 to 1.20), the northwestern and northern portion for temporal variation (having a trend in the cluster ranged from -6.25% to 83.93). This study provides an overall picture of APOs that presented downward trends over time, seasonal fluctuation, and clustered patterns across space and over time in Henan Province-the most populated province in China. The findings of this study warrant future studies to investigate underlying influential factors of spatial variation of APOs.

NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer.

Netrin-4 (NTN4), a member of neurite guidance factor family, can promote neurite growth and elongation. This study aims to investigate if NTN4 correlates with prognosis and immune infiltration in breast cancer. The prognostic landscape of NTN4 and its relationship with immune infiltration in breast cancer were deciphered with public databases and immunohistochemistry (IHC) in tissue samples. The expression profiling and prognostic value of NTN4 were explored using UALCAN, TIMER, Kaplan-Meier Plotter and Prognoscan databases. Based on TIMER, relationships of NTN4 expression with tumor immune invasion and immune cell surface markers were evaluated. Transcription and survival analyses of NTN4 in breast cancer were investigated with cBioPortal database. The STRING database was explored to identify molecular functions and signaling pathways downstream of NTN4. NTN4 expression was significantly lower in invasive breast carcinoma compared with adjacent non-malignant tissues. Promoter methylation of NTN4 exhibited different patterns in breast cancer. Low expression of NTN4 was associated with poorer survival. NTN4 was significantly positively related to infiltration of CD8+ T cells, macrophages and neutrophils, whereas significantly negatively related to B cells and tumor purity. Association patterns varied with different subtypes. Various associations between NTN4 levels and immune cell surface markers were revealed. Different subtypes of breast cancer carried different genetic alterations. Mechanistically, NTN4 was involved in mediating multiple biological processes including morphogenesis and migration.

Weather and Birth Weight: Different Roles of Maternal and Neonatal GPR61 Promoter Methylation.

Objectives: It is unclear whether G protein-coupled receptor 61 (GPR61) affecting body weight, plays a role in the association between birth weight and weather. This study aimed to assess the effects of prenatal weather and GPR61 on birth weight. Methods: A total of 567 mother-newborn pairs were recruited in Houzhai Center Hospital during 2011-2012. We detected the maternal and neonatal GPR61 promoter methylation levels, and obtained meteorological and air pollution data. Results: A positive association was observed between maternal and neonatal GPR61 methylation levels, and both of them were affected by precipitation, relative humidity (RH) and daily temperature range (DTR). Birth weight was associated negatively with RH and positively with DTR ( P < 0.05). A significant association was observed between birth weight and neonatal GPR61 methylation. We observed that maternal GPR61 methylation seemed to modify associations between weather and birth weight ( P interaction < 0.10), while neonatal GPR61 methylation mediated the effects of RH and DTR on birth weight ( P < 0.05). Conclusions: Our findings revealed the significant associations among prenatal weather, GPR61 methylation and birth weight. Maternal GPR61 methylation may modify the susceptibility of birth weight to prenatal weather conditions, while neonatal GPR61 methylation may be a bridge of the effects of prenatal RH and DTR on birth weight.

The type of previous abortion modifies the association between air pollution and the risk of preterm birth.

BACKGROUND: Air pollution and previous abortion have been reported to be related to preterm birth (PTB). But rare study examined the effect of air pollution on PTB risk among mothers with previous abortion. OBJECTIVE: To estimate the effect of air pollution on PTB and the potential effect modification of previous abortion on such an association in rural part of Henan province (China). METHOD: Based on National Free Preconception Health Examination Project (NFPHEP), information from the medical records of 57,337 mothers with previous abortion were obtained. An inverse distance-weighted model was used to estimate exposure levels of air pollutants. The effect of air pollution on the risk of PTB was estimated with a multiple logistic regression model. Stratified and interaction analyses were undertaken to explore the potential effect modification of previous abortion on this association. RESULTS: The risk of PTB was positively associated with exposure to levels of nitrogen dioxide (NO2; OR: 1.03; 95%CI: 1.02-1.04)], and sulfur dioxide (SO2; 1.04; 1.02-1.07), and negatively associated with ozone (O3) exposure (0.97; 0.97-0.98) during the entire pregnancy. Besides, we observed a positive effect of carbon monoxide (CO) exposure during the third trimester of pregnancy on PTB (1.14; 1.01-1.29). The type of previous abortion could modify the effect of air pollution on the PTB risk (P-interaction < 0.05). Compared with mothers with previous induced abortion, mothers with previous spontaneous abortion carried a higher risk of PTB induced by NO2, CO, and O3. CONCLUSIONS: The risk of PTB was positively associated with levels of NO2, SO2 and CO, and negatively associated with the O3 level. The types of previous abortion could modify the effect of air pollution on PTB. Mothers who had an abortion previously, especially spontaneous abortion, should avoid exposure to air pollution to improve their pregnancy outcome.