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Yue-Yu Shi,1 Xing-Lei Chen,1 Qian-Xin Chen,1 Yuan-Zhong Yang,2 Meng Zhou,1 Yue-Xiang Ren,3 Lu-Ying Tang,3 Ze-Fang Ren1 1School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2The Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Ze-Fang Ren, School of Public Health, Sun Yat-sen University, 74 Zhongshan 2nd Road, Guangzhou, Guangdong, People’s Republic of China, Tel/Fax +86-20-87332577, Email renzef@mail.sysu.edu.cn Lu-Ying Tang, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong, People’s Republic of China, Tel +86-20-85253000, Fax +86-20-85253336, Email tangly@mail.sysu.edu.cnPurpose: Enolase-1 (ENO1) plays a key role in malignancies. Previous studies on the association between ENO1 expression and breast cancer prognosis had yielded inconsistent results. In the present study, we assessed the prognostic effect of ENO1 in breast cancer using Guangzhou Breast Cancer Study (GZBCS) cohort with full consideration of the potential confounders and the modification effects. The results were further validated in the TCGA-BRCA cohort and explained by tumor immunity.Methods: ENO1 protein expressions were evaluated by immunohistochemistry in tissue microarrays from 961 patients with primary invasive breast cancer. Chi-square tests were used to assess the association of ENO1 levels with the patient’s characteristics. Cox regression models were applied to assess the prognostic effects. The TCGA-BRCA cohort was utilized to validate the results and explore the potential mechanisms. The immune infiltration was determined using the CIBERSORT and ssGSEA algorithms; the correlation between ENO1 expression and the abundance of tumor-infiltrating immune cells (TIICs) and scores of immune-related functions was evaluated by Wilcoxon signed-rank tests and Spearman’s rank test.Results: ENO1 protein expression exerted a protective effect on OS in stage I/II patients (HR=0.58, 95% CI: 0.35– 0.96) but not in stage III patients (HR=1.42, 95% CI: 0.81– 2.49, P interaction=0.04) in GZBCS; consistent results were obtained at mRNA levels in TCGA cohort. Immune infiltration analyses revealed that ENO1 was positively correlated with multiple antitumor TIICs (including M1 macrophages, B cells, CD8 T cells, T helper 2 cells, and NK cells) only in stage I/II but not stage III patients.Conclusion: A higher expression of ENO1 was associated with a better prognosis only in early-stage breast cancer, which may be related to the different effects of ENO1 on immune infiltration, suggesting that ENO1 may be a promising target for precision immunotherapy in breast cancer.Keywords: ENO1, breast cancer, prognosis, tissue microarray, tumor-infiltrating immune cells

Background: Previous studies have found that acute febrile infection may decrease the risk of breast cancer. Meanwhile, it is well known that interleukin-6 (IL6) played dual roles in the tumor microenvironment. Fever may stimulate IL6 production, and IL6 rs1800796 also influences the expression of IL6. However, the impact of fever and its interaction with IL6 rs1800796 on breast cancer survival remains to be explored. Methods: This was a prospective cohort study of 4,223 breast cancer patients. Exposures were pre-/postdiagnostic infection-induced fever and rs1800796 polymorphism. The endpoints were overall survival (OS) and progression-free survival (PFS). Adjusted hazard ratios were obtained using multivariate Cox proportional hazards regression models. Results: Compared with women without prediagnostic fever, the adjusted hazard ratio (HR) of progression for those with prediagnostic fever was 0.81 (95% CI, 0.66–0.99), particularly for the CC genotype of IL6 rs1800796 (HR, 0.53; 95% CI, 0.36–0.79). OS was also better (HR, 0.59; 95% CI, 0.36–0.99) among women with the CC genotype exposed to prediagnostic fever, accompanied by a significant interaction (P = 0.021). Postdiagnostic fever conferred better PFS for breast cancer (HR, 0.72; 95% CI, 0.52–1.00). Irrespective of the genotype of IL6, lymph node–positive women with postdiagnostic fever (HR, 0.57; 95% CI, 0.37–0.89) had a lower risk of progression than lymph node–negative women (HR, 1.12; 95% CI, 0.70–1.79). Conclusions: Infection-induced fever was beneficial to breast cancer survival, particularly for women who were the CC genotype of IL6 rs1800796 or node positive. Impact: This study provides new insight into the roles of infection-induced fever as a potential prognostic marker and therapy regimen for breast cancer.

Purpose: Increasing crop yield to ensure global food security while decreasing carbon footprint (CF) is a challenge for sustainable agriculture. Although intercropping is suggested as a potential pathway in this regard, the balance between yield advantage and CF is unclear, especially under different nitrogen (N) application rates. Methods: A two-year field experiment was conducted to investigate the effect of oat/sunflower intercropping and N application rates (0, 50, 100, and 150 kg ha−1) on yield advantages, N uptake, and CF. Results: The overall land equivalent ratio of oat/sunflower intercropping decreased from 1.33 to 1.07 with increasing N fertilization, which implies the potential N reduction to maintain crop yield. Without fertilization, the yield advantage of intercropping was 28–32% and 18–47% higher for oat and sunflower, respectively compared with corresponding monocultures. However, this yield advantage decreased with increasing fertilization, especially for oat. The border rows contributed more than one-third of the yield for intercropped oat without N fertilization, but their contribution decreased with increasing N fertilization. However, the contribution of border rows to intercropped sunflower yield was independent of N fertilization and remained around 69–75%. Overall, oat/sunflower relay strip intercropping maximizes the productivity by border row effects due to reduced N fertilization demand. Furthermore, intercropping decreased the CF relative to monoculture, especially without N fertilization. Conclusion: Intercropping can act as a win–win strategy for sustainable agriculture in Northwest China with higher productivity and lower carbon footprint.

Lung cancer has become a global health issue in recent decades. Approximately 80-85% of cases are non-small-cell lung cancer (NSCLC). Despite the high rate of resistance, cisplatin-base chemotherapy is still the main treatment for NSCLC patients. Thus, overcoming cisplatin resistance is urgently needed in NSCLC therapy. In this study, we identify NADPH metabolism and reactive oxygen species (ROS) levels as the main causes accounting for cisplatin resistance. Based on a small panel consisting of common chemotherapy drugs or compounds, APR-246 is proved to be an effective compound targeting cisplatin-resistant NSCLC cells. APR-246 specially inhibits proliferation and colony formation of cisplatin-resistant cells. In details, APR-246 can significantly cause G0/G1 accumulation and S phase arrest of cisplatin resistant cells and gives rise to severe mitochondria dysfunction as well as elevated apoptosis. Further study proves that it is the aberrant ROS levels as well as NRF2/SLC7A11/GSH axis dysfunction accounting for the specific antitumor effects of APR-246. Scavenging ROS with N-acetylcysteine (NAC) disrupts the inhibitory effect of APR-246 on cisplatin-resistant cells. Mechanistically, NRF2 is specifically degraded by the proteasome following its own ubiquitylation in APR-246-treated cisplatin-resistant cells, which in turn decreases NRF2/SLC7A11/GSH axis activity. Our study provides new insights into the biology driving cisplatin resistance of lung cancer and highlights APR-246 as a potential therapeutic reagent for overcoming cisplatin resistance.

Context Longitudinal patterns of resting heart rate (RHR) in patients with diabetes mellitus and their association with health outcomes are not well-characterized. Objective We sought to explore the RHR trajectories in patients with diabetes mellitus and their association with cardiovascular disease (CVD) and all-cause mortality. Design The Kailuan Study is a prospective cohort study. Participants underwent health examinations biennially starting in 2006 and were followed until December 31, 2020. Setting General community. Participants A total of 8218 diabetic participants who attended at least 3 of the examinations conducted in 2006, 2008, 2010, and 2012 were included. Main outcome measures CVD and all-cause mortality. Results We identified 4 RHR trajectories in participants with diabetes mellitus between 2006 and 2012: low-stable (range, 66.83-64.91 beats/min; n = 1705), moderate-stable (range, 76.30-76.95 beats/min; n = 5437), high-decreasing (mean decreased from 92.14 to 85.60 beats/min; n = 862), and high-increasing (mean increased from 84.03 to 111.62 beats/min; n = 214). During an average follow-up of 7.25 years, 977 cases of CVD and 1162 deaths were identified. Compared with the low-stable trajectory, adjusted hazard ratios (HRs) for CVD were 1.48 (95% CI, 1.02-2.14; P = .04) for the high-increasing trajectory, adjusted HRs for all-cause mortality were 1.34 (95% CI, 1.14-1.58; P < .01) for the moderate-stable trajectory, 1.68 (95% CI, 1.35-2.10; P < .01) for the high-decreasing trajectory, and 2.47 (95% CI, 1.85-3.31; P < .01) for the high-increasing trajectory. Conclusions RHR trajectories were associated with the subsequent risks of CVD and all-cause mortality in patients with diabetes mellitus.

The interfacial thermal transport between graphene and β-Ga2O3 is systematically investigated using molecular dynamics simulation.

Thermo-optic (TO) phase shifters are very fundamental units in large-scale active silicon photonic integrated circuits (PICs). However, due to the limitation of microheater materials with a trade-off between heating efficiency and absorption loss, designs reported so far typically suffer from slow response time, high power consumption, low yields, and so on. Here, we demonstrate an energy-efficient, fast-response, and low-loss TO phase shifter by introducing hydrogen-doped indium oxide (IHO) films as microheater, and the optimized electron concentration with enhanced mobility endows the IHO high conductivity as well as high near-infrared (NIR) transparency, which allow it to directly contact the silicon waveguide without any insulating layer for efficient tuning and fast response. The TO phase shifter achieves a sub-microsecond response time (970 ns/980 ns) with a {\pi} phase shift power consumption of 9.6 mW. And the insertion loss introduced by the IHO microheater is ~ 0.5 dB. The proposed IHO-based microheaters with compatible processing technology illustrate the great potential of such material in the application of large-scale silicon PICs., Comment: 10 pages, 4 figures, journal

Additional file 2. Original data of western blotting.

Additional file 1:Supplementary Fig. 1. Flow chart of data analysis in this study. Supplementary Table 1. Parameters of two risk equations used in this study for men and women. Supplementary Table 2. Comparison of research objects between man and woman. Supplementary Table 3.1. Screening variable subsets based on Cox regression in man. Supplementary Table 3.2. Screening variable subsets based on Lasso-Cox regression in man. Supplementary Table 3.3. Screening variable subsets based on RSF in man. Supplementary Table 3.4. Screening variable subsets based on Cox regression in woman. Supplementary Table 3.5. Screening variable subsets based on Lasso-Cox regression in woman. Supplementary Table 3.6. Screening variable subsets based on RSF in woman. Supplementary Table 4. C statistic of different models on training and test sets.

In a recurrent setting, conventional approaches to neural architecture search find and fix a general model for all data samples and time steps. We propose a novel algorithm that can dynamically search for the structure of cells in a recurrent neural network model. Based on a combination of recurrent and recursive neural networks, our algorithm is able to construct customized cell structures for each data sample and time step, allowing for a more efficient architecture search than existing models. Experiments on three common datasets show that the algorithm discovers high-performance cell architectures and achieves better prediction accuracy compared to the GRU structure for language modelling and sentiment analysis.

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary arterial pressure. This occurs due to abnormal remodeling of small peripheral lung vasculature resulting in progressive occlusion of the artery lumen that eventually causes right heart failure and death. Current therapeutic options for PAH are limited and focused mainly on reversal of pulmonary vasoconstriction and proliferation of vascular cells. Although these treatments can relieve disease symptoms, PAH remains a progressive lethal disease.Bone morphogenetic proteins (BMPs) and their receptors were required for PAH-induced right ventricular hypertrophy. Emerging data suggest that restoration of BMP type II receptor (BMPR2) signaling in PAH is a promising alternative that could prevent and reverse pulmonary vascular remodeling. BMPR2 mutations have been identified in >70% of familial and roughly 15% of sporadic PAH cases. Wingless (Wnt) are a family of secreted glycoproteins with varying expression patterns and a range of functions, Wnt signaling pathway is divided into canonical signaling pathway and non-canonical signaling pathway. A recent study reports that interaction between BMP and Wnt closely associated with lung development, those cascade coordination regulation stem cell fate which determine lung branching morphogenes. The promoting effect of BMPR2 on proliferation, survival, and motility of endothelial cells was through recruiting Wnts signaling pathway, the interaction between BMP and Wnt closely associated with lung development.Therefore, in this review, we outline the latest advances of BMP and Wnt signaling pathway in the pathogenesis of PAH and disease progression.

Thin-film Schottky barrier diodes (SBDs) based on amorphous oxide semiconductors play an important role in flexible and wearable electronics. In this work, thin-film SBDs based on indium–gallium–zinc oxide (InGaZnO or IGZO) were fabricated with sputtered PdO x /Pd top Schottky contact and low-temperature (100 °C) annealing in air atmosphere. PdO x produces an oxygen-rich stoichiometry in the Schottky interface, resulting in high-quality contact with rather low interface trap state density of $2.6\times 10^{17}$ cm−3 and extremely low barrier inhomogeneity of 0.01 eV. As a result, high-performance IGZO SBDs were achieved with high ON/ OFF ratio of $3\times 10^{7}$ , near–unity ideality factor of 1.04, barrier height of 0.85 eV, high ON-current density of 2.5 $\text{A}\cdot $ cm−2 at 1 V, and high reverse breakdown voltage of ~12 V.

The prior literature on analyst forecasts has focused almost exclusively on firms that just meet or beat the mean or median consensus analyst forecast, without much regard to alternative benchmarks within the forecast distribution. Anecdotal evidence suggests that there is institutional significance to the lowest (minimum) and highest (maximum) analyst earnings forecast. We rigorously explore whether these two new benchmarks actually have incremental significance and, if so, whether there are differences in how managers and investors perceive the importance of these three benchmarks (i.e., minimum, mean, and maximum). Consistent with the theory of investor ambiguity aversion, which predicts an asymmetric market response to good and bad news, our results support the notion that of the three benchmarks we explore, firms act most aggressively to exceed the minimum forecast, followed by the mean, and then finally the maximum. This order is consistently supported by the following evidence: the existence of higher incentives to beat the benchmark; the likelihood of earnings management to beat the benchmark; accrual reversal after firms just barely achieve each benchmark; accrual mispricing around each benchmark; and, finally, a faster incorporation into the stock price of the bad news that a firm misses the minimum than of the good news that a firm meets or beats the maximum. These findings fill a void in academic research on these two new benchmarks and offer a consistent explanation as to why the popular press and managers frequently highlight and discuss beating these benchmarks as a separate and notable achievement. This paper was accepted by Brian Bushee, accounting. Funding: Q. Xin gratefully acknowledges the financial support from the “Shenzhen Peacock Plan” start-up research [Grant GA11409004] and the Shenzhen Key Research Base of Humanities and Social Sciences [Grant KP191001]. Supplemental Material: The data files and online appendix are available at https://doi.org/10.1287/mnsc.2022.4609 .

ObjectivesPrevious studies have confirmed the relations between inter-arm systolic blood pressure difference (IASBPD) and carotid artery plaque with the risk of cardiovascular diseases (CVD). But it is unclear whether the combined effect of IASBPD and carotid artery plaque further increases the risk of CVD and all-cause mortality.Materials and methodsWe enrolled 4,970 participants (≥40 years old) in the prospective Kailuan study. All participants underwent dual-arm blood pressure and carotid artery ultrasounds. IASBPD was the absolute value of the difference between dual-arm blood pressure. All the participants were divided into four groups according to their IASBPD levels and the presence or absence of carotid artery plaque and Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence interval (CI) for incident CVD and all-cause mortality.ResultsDuring a median follow-up of 7 years, 179 CVD events and 266 deaths occurred. Multivariable Cox Regression showed that participants with IASBPD ≥ 10 mmHg and plaque had a significantly higher incidence of CVD, cerebral infarction (CI), and myocardial infarction (10, 7.27, and 1.36%, respectively). After adjusting for covariates, the IASBPD ≥ 10 mmHg and carotid plaque group significantly increased risks for CVD (HR 2.38; 95% CI, 1.40∼4.05), CI (HR, 2.47; 95% CI, 1.31∼4.67), and all-cause mortality (HR, 2.08; 95% CI, 1.20∼3.59).ConclusionOur study indicated that the combination of IASBPD and carotid artery plaque was associated with incident CVD and all-cause mortality.

Bone injury plagues millions of patients worldwide every year, and it demands a heavy portion of expense from the public medical insurance system. At present, orthopedists think that autologous bone transplantation is the gold standard for treating large-scale bone defects. However, this method has significant limitations, which means that parts of patients cannot obtain a satisfactory prognosis. Therefore, a basic study on new therapeutic methods is urgently needed. The in-depth research on crosstalk between macrophages (Mϕs) and bone marrow mesenchymal stem cells (BMSCs) suggests that there is a close relationship between inflammation and regeneration. The in-depth understanding of the crosstalk between Mϕs and BMSCs is helpful to amplify the efficacy of stem cell-based treatment for bone injury. Only in the suitable inflammatory microenvironment can the damaged tissues containing stem cells obtain satisfactory healing outcomes. The excessive tissue inflammation and lack of stem cells make the transplantation of biomaterials necessary. We can expect that the crosstalk between Mϕs and BMSCs and biomaterials will become the mainstream to explore new methods for bone injury in the future. This review mainly summarizes the research on the crosstalk between Mϕs and BMSCs and also briefly describes the effects of biomaterials and aging on cell transplantation therapy.

Background Cellular experiments revealed that a decreased histone H3 lysine 9 trimethylation (H3K9me3) level was associated with the upregulation of oncogenes in breast cancer cells. Moreover, the role of H3K9me3 in breast cancer was closely associated with estrogen receptor (ER) status. Therefore, we aimed to examine the prognostic value of H3K9me3 on breast cancer by ER status. The level of H3K9me3 in tumors were evaluated with tissue microarrays by immunohistochemistry for 917 women diagnosed with primary invasive breast cancer. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction between H3K9me3 and ER on the prognosis was assessed on multiplicative scale. Results The level of H3K9me3 in tumor tissues was lower than that in adjacent tissues. The high level of H3K9me3 was associated with a better OS (HR = 0.43, 95% CI: 0.21–0.86) and PFS (HR = 0.49, 95% CI: 0.29–0.81) among only ER-positive but not ER-negative tumors. Moreover, the interaction between the level of H3K9me3 and ER status (negative and positive) on the prognosis was significant (Pinteraction = 0.011 for OS; Pinteraction = 0.022 for PFS). Furthermore, the ER-positive tumors were stratified by ER-low and ER-high positive tumors, and the prognostic role of H3K9me3 was significant among only ER-high positive patients (HR = 0.34, 95% CI: 0.13–0.85 for OS; HR = 0.47, 95% CI: 0.26–0.86 for PFS). Conclusions Our study showed that the prognostic value of H3K9me3 on breast cancer was related to ER status and expression level, and the high level of H3K9me3 was associated with a better prognosis among ER-positive tumors, particularly ER-high positive tumors.

Self-powered UV photodetectors and imaging arrays based on p-type NiO/n-type InGaZnO (IGZO) heterojunctions are fabricated at room temperature by using ratio-frequency magnetron sputtering. The p-n heterojunction exhibits typical rectifying characteristics with a rectification ratio of 7.4×104 at a ±4 V applied bias. A high photo-responsivity of 28.8 mA/W is observed under zero bias at a wavelength of 365 nm. The photodetector possesses a fast response time of 15 ms which is among the best in reported oxide-based p-n junction-based UV photodetectors. Finally, recognition of an “H” pattern is demonstrated by a 10×10 photodetector array at zero bias. The results indicate that the NiO/IGZO based photodetectors may have a great potential in constructing large-scale self-powered UV imaging systems.

Whereas the critical roles of innate lymphoid cells (ILCs) in adult are increasingly appreciated, their developmental hierarchy in early human fetus remains largely elusive. In this study, we sorted human hematopoietic stem/progenitor cells, lymphoid progenitors, putative ILC progenitor/precursors and mature ILCs in the fetal hematopoietic, lymphoid and non-lymphoid tissues, from 8 to 12 post-conception weeks, for single-cell RNA-sequencing, followed by computational analysis and functional validation at bulk and single-cell levels. We delineated the early phase of ILC lineage commitment from hematopoietic stem/progenitor cells, which mainly occurred in fetal liver and intestine. We further unveiled interleukin-3 receptor as a surface marker for the lymphoid progenitors in fetal liver with T, B, ILC and myeloid potentials, while IL-3RA– lymphoid progenitors were predominantly B-lineage committed. Notably, we determined the heterogeneity and tissue distribution of each ILC subpopulation, revealing the proliferating characteristics shared by the precursors of each ILC subtype. Additionally, a novel unconventional ILC2 subpopulation (CRTH2– CCR9+ ILC2) was identified in fetal thymus. Taken together, our study illuminates the precise cellular and molecular features underlying the stepwise formation of human fetal ILC hierarchy with remarkable spatiotemporal heterogeneity.

P-type tin monoxide (SnO) thin-film phototransistors were developed with high photoresponsivity of $2.94\times 10^{{5}}$ A/W and high detectivity of $1.82\times 10^{{14}}$ Jones, and these values are, to the best of our knowledge, among the highest for the reported oxide-semiconductor-based phototransistors. The excellent performances of these phototransistors were further demonstrated by incorporating the devices into a ${10}\times {10}$ array to successfully image a letter “A” pattern. Furthermore, by integration of n-type indium gallium zinc oxide and p-type SnO thin-film phototransistors, we realized a complementary photosensitive inverter. The inverter exhibits excellent photoresponse with a high voltage gain rate change of 194%. Our results indicates that the SnO based phototransistors have great potential in thin-film photoelectronic circuits and systems.

Neuromorphic electronics, which use artificial photosensitive synapses, can emulate biological nervous systems with in-memory sensing and computing abilities. Benefiting from multiple intra/interactions and strong light-matter coupling, two-dimensional heterostructures are promising synaptic materials for photonic synapses. Two primary strategies, including chemical vapor deposition and physical stacking, have been developed for layered heterostructures, but large-scale growth control over wet-chemical synthesis with comprehensive efficiency remains elusive. Here we demonstrate an interfacial coassembly heterobilayer films from perylene and graphene oxide (GO) precursors, which are spontaneously formed at the interface, with uniform bilayer structure of single-crystal perylene and well-stacked GO over centimeters in size. The planar heterostructure device exhibits an ultrahigh specific detectivity of 3.1 × 1013 Jones and ultralow energy consumption of 10−9 W as well as broadband photoperception from 365 to 1550 nm. Moreover, the device shows outstanding photonic synaptic behaviors with a paired-pulse facilitation (PPF) index of 214% in neuroplasticity, the heterosynapse array has the capability of information reinforcement learning and recognition.

The underlying mechanism behind the deteriorated laying performance of aged laying hens remains unclear. In the present study, the laying performance and gene expression along the hypothalamus-pituitary-gonad axis were determined. A total of 300 healthy 90-wk-old ISA hens with similar body weights were classified into three groups according to their laying rate between 90 and 94 wk of age. The experimental groups were the low laying rate (60%, LLR), high laying rate (85%, HLR), and intermediate laying rate (60%laying rate85%, MLR) hens. At the end of 94 wk of age, eight hens were randomly selected from each group for tissue collection. The gene expression of hormones and their receptors were determined in the hypothalamus, pituitary, and follicles. The results showed that the serum 17-β-estradiol had no significant difference among the three groups. However, the level of insulin-like growth factor 1 (IGF1) in LLR hens was significantly decreased in the serum, small white follicles (SWF), and dominant follicles (DF, P0.05). Within the hypothalamus and small yellow follicles (SYF), the mRNA expression level of estrogen receptor was higher in the MLR group (P0.05). Compared with HLR hens, the steroid hormone-synthesis key gene, CYP19A1 was significantly decreased in the SWF of MLR-hens and DF of MLR- and LLR-hens (P0.05). The mRNA expression level of IGF1 receptor was higher in the hypothalamus, pituitary, SWF, large white follicles (LWF), SYF, and DF of LLR hens, compared to the HLR hens (P0.05). These results suggest that decreased IGF1 in serum and follicles was associated with the decreased egg production of aged laying hens. The present study provides novel insights into the endocrine changes in aged hens having different egg production.The level of insulin-like growth factor 1 (IGF1) in low laying rate hens was significantly decreased in the serum, small white follicles, and dominant follicles. In the hypothalamus and small yellow follicles, the mRNA expression level of estrogen receptor in low laying rate hens was higher than in the medium laying rate hens. Compared with the high laying rate hens, the steroid hormone-synthesis gene, CYP19A1 was significantly decreased in the small white and dominant follicles of medium laying rate hens, as well as in the dominant follicles of low laying rate hens. Additionally, the mRNA expression level of IGF1 receptor was increased in the hypothalamus, pituitary, small white follicles, large white follicles, small yellow follicles, and dominant follicles of low laying rate hens compared to the high laying rate hens. These results suggest that decreased IGF1 in the serum and follicles of laying hens was associated with the reduction in the egg production of aged laying hens. The present study provides novel insights into the endocrine changes in aged laying hens having different egg production performances.

A new wood-rotting fungal species, Punctularia bambusicola, is proposed based on a combination of morphological features and molecular data. The species is characterized by resupinate, lilac to purple basidiomata, pink to rose tuberculate hymenial surface, monomitic hyphal system with clamped generative hyphae, yellowish to brown dendrohyphidia and ellipsoid basidiospores measuring 6.5–8.5 × 3.5–5 µm. Phylogenetic analyses of combining ITS and LSU nrRNA gene regions demonstrated that P. bambusicola forms a single lineage sister to P. atropurpurascens with strong statistical supports (100% BS, 100% BT, 1.00 BPP).

Background Low-risk individuals are unlikely to benefit from noninvasive testing, and women tend to have a lower prevalence of obstructive coronary artery disease (CAD). This study compared the performance of two current guidelines that differ by sex to assess stable chest pain outpatients, including symptom-based (2016 National Institute for Health and Care Excellence, NICE) and risk-based strategies (2019 European Society of Cardiology, ESC). Methods A total of 542 men and women outpatients referred for coronary computed tomography angiography (CCTA) at a single-centre were retrospectively included in this study. A risk assessment was calculated for each outpatient according to the NICE and ESC guidelines. Patients were classified into low-risk and high-risk groups according to each strategy. The presence of obstructive coronary artery disease was the endpoint. Net reclassification improvement (NRI) was used to assess the performance of the two strategies. Results The 2016 NICE guidelines classified 29.39% of women and 34.60% of men into the low-risk group. The 2019 ESC guidelines classified 55.56% of women and 28.14% of men into the low-risk group. The 2019 ESC guidelines had a higher predictive value for coronary artery disease compared to the 2016 NICE guidelines, with a positive NRI in men (15.55%) and women (36.59%) respectively. Conclusion The 2019 ESC guidelines offered a more accurate calculation of risk assessment than the 2016 NICE guidelines. Patient sex influenced applying the recent ESC guidelines, which would result in a significant decrease in inappropriate testing of women but an increase in appropriate noninvasive testing of men.

Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan–Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271–285 of FOXA1 expression increased from 0.35 (95% CI 0.14–0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35–6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P

Human skeletal stem cells (SSCs) have been discovered in fetal and adult long bones. However, the spatiotemporal ontogeny of human embryonic SSCs during early skeletogenesis remains elusive. Here we map the transcriptional landscape of human limb buds and embryonic long bones at single-cell resolution to address this fundamental question. We found remarkable heterogeneity within human limb bud mesenchyme and epithelium, and aligned them along the proximal–distal and anterior–posterior axes using known marker genes. Osteo-chondrogenic progenitors first appeared in the core limb bud mesenchyme, which give rise to multiple populations of stem/progenitor cells in embryonic long bones undergoing endochondral ossification. Importantly, a perichondrial embryonic skeletal stem/progenitor cell (eSSPC) subset was identified, which could self-renew and generate the osteochondral lineage cells, but not adipocytes or hematopoietic stroma. eSSPCs are marked by the adhesion molecule CADM1 and highly enriched with FOXP1/2 transcriptional network. Interestingly, neural crest-derived cells with similar phenotypic markers and transcriptional networks were also found in the sagittal suture of human embryonic calvaria. Taken together, this study revealed the cellular heterogeneity and lineage hierarchy during human embryonic skeletogenesis, and identified distinct skeletal stem/progenitor cells that orchestrate endochondral and intramembranous ossification.

Oxide semiconductors have emerged as ideal candidate materials for flexible electronics and circuits. However, complementary flip-flops, which are the essential building blocks in sequential circuits, based on all-oxide thin-film transistors (TFTs) have not yet been demonstrated. Here, we employed n-type indium gallium zinc oxide and p-type tin monoxide to achieve J-K flip-flop (JK-FF) and D-type edge-triggered FF (D-FF). The operation properties of the JK-FF and D-FF were characterised both statically and dynamically. The output signals of the D-FF show great robustness. The D-FF shows very short propagation delay times of 17 and $40~\mu \text{s}$ from “0” to “1” and from “1” to “0”, respectively. Based on the D-FFs, a two-bit counter with 90 transistors was designed and fabricated successfully, acting as either up-counter or down-counter. To the best of our knowledge, this counter has the highest integration among the reported thin-film complementary sequential circuits based on all-oxide transistors to date.

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.

Dual-gate (DG) Ion-sensitive thin-film transistor (ISTFT) pH sensors based on tin oxide (SnOx) channel and Al2O3 sensor membrane have been developed. DG SnOx thin film transistors with Al2O3 dielectrics were fabricated, illustrating effective linear current modulation under top gate bias. The SnOX DG-ISTFTs with 10-nm Al2O3 sensor membrane can operate at a low single supply voltage of −1.0 V with a low power consumption around 3 $\mu \text{W}$ . In contrast to most reported ISTFT pH sensors, which show linear dependence of pH value on threshold voltage, and are not directly readable, the SnOx DG-ISTFTs exhibit linear pH dependence on directly readable drain current. We demonstrate a high sensitivity of 83.87 nA/pH and a low current hysteresis of 1.65 nA after a pH loop of 7-10-7-4-7. This enables significantly simplified readout circuits with reduced power consumption. The SnOx based DG-ISTFTs may have huge practical potential as portable and wearable biosensors and chemical sensors.

Two lanthanide coordination polymers (CPs) with the chemical formulae of [Pr(HPIDC)(C2O4)0.5(H2O)]n (1, H3PIDC = 2-(pyridine-2-yl)-1H-imidazole-4,5-dicarboxylic acid and H2C2O4 = oxalic acid) and [...

Graphene/β-Ga

Neuromorphic electronics, which use artificial photosensitive synapses, can emulate biological nervous systems with in-memory sensing and computing abilities. Benefiting from multiple intra/interactions and strong light-matter coupling, two-dimensional heterostructures are promising synaptic materials for photonic synapses. Two primary strategies, including chemical vapor deposition and physical stacking, have been developed for layered heterostructures, but large-scale growth control over wet-chemical synthesis with comprehensive efficiency remains elusive. Here we demonstrate an interfacial coassembly heterobilayer films from perylene and graphene oxide (GO) precursors, which are spontaneously formed at the interface, with highly uniform bilayer structure of single-crystal perylene and well-stacked GO over centimeters in size. The planar heterostructure device exhibits an ultrahigh specific detectivity of 5.01×1016 Jones and ultralow energy consumption of 10− 9 W as well as broadband photoperception from 365 to 1550 nm. Moreover, the device shows extraordinary photonic synaptic behaviors with a paired-pulse facilitation (PPF) index of 214% in neuroplasticity, and the heterosynapse array has the capability of information reinforcement learning and recognition.

Nutrition during the pre-lay period takes effect on the production performance in the laying flock. This study evaluated the effects of dietary energy and protein levels in pre-lay diet on performance during the whole laying period and the egg quality, bone quality, and mRNA expression of hypothalamus-pituitary-gonadal (HPG) axis-related genes of hens at the end of the laying cycle. A total of 1,856 15-wk old Hy-Line brown pullets were randomly assigned to one of the four dietary treatments: using a 2 × 2 factorial arrangement with 2 energy levels (2,700 and 2,800 kcal/kg ME, respectively) and 2 protein levels (15 and 16.5% CP, respectively). Pullets were fed ad libitum from 15 to 20 wk and from 20 wk onward, fed with a similar laying diet till 72 wk of age. At 72 wk, the expression of genes in the hypothalamus, pituitary, ovarian, and follicles and bone quality was evaluated. At 72wk, there were no differences in production performance, BW, organ index, and ovarian parameters among the dietary treatments. High-CP diet increased the egg shape index and eggshell thickness (p < 0.05), but the eggshell breaking strength, Haugh unit, and albumen height did not differ among the treatments. Neither dietary energy nor protein level took an effect of bone quality. Low-energy diet increased the mRNA expression of gonadotropin-releasing hormone-1 (GnRH-1) in the hypothalamus (p < 0.05). The mRNA expression level of estrogen receptor-1 (ESR-1) in the hypothalamus and ovary was elevated by the 2,700 ME-15%CP diet (p < 0.05). The expression of cytochrome family 17 subfamily A polypeptide 1 (CYP17A1) in the large white follicle (LWF), small yellow follicles (SYF) and dominant follicle (DF) was decreased by the 2,800 kcal/kg diet (p < 0.05). These results indicate that the prelay diet had no influence on the production performance but had minimal effect on the eggshell characteristics and bone parameters. These results suggest that the energy and protein level of the prelay diet changes the expression of HPG axis-related genes of hens around the end of the laying cycle without changing the circulating sex hormone profile. The effect of prelay diet on the endocrinal adjustment at the end of the laying cycle needs to be investigated further.