Measurement of 19F(p, γ)20Ne reaction suggests CNO breakout in first stars.

Proposed mechanisms for the production of calcium in the first stars (population III stars)-primordial stars that formed out of the matter of the Big Bang-are at odds with observations1. Advanced nuclear burning and supernovae were thought to be the dominant source of the calcium production seen in all stars2. Here we suggest a qualitatively different path to calcium production through breakout from the 'warm' carbon-nitrogen-oxygen (CNO) cycle through a direct experimental measurement of the 19F(p, γ)20Ne breakout reaction down to a very low energy point of 186 kiloelectronvolts, reporting a key resonance at 225 kiloelectronvolts. In the domain of astrophysical interest2, at around 0.1 gigakelvin, this thermonuclear 19F(p, γ)20Ne rate is up to a factor of 7.4 larger than the previous recommended rate3. Our stellar models show a stronger breakout during stellar hydrogen burning than previously thought1,4,5, and may reveal the nature of calcium production in population III stars imprinted on the oldest known ultra-iron-poor star, SMSS0313-67086. Our experimental result was obtained in the China JinPing Underground Laboratory7, which offers an environment with an extremely low cosmic-ray-induced background8. Our rate showcases the effect that faint population III star supernovae can have on the nucleosynthesis observed in the oldest known stars and first galaxies, which are key mission targets of the James Webb Space Telescope9.

HIF-1-regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/ß-catenin pathway activation.

Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24-CD44+ cells, and aldehyde dehydrogenase-expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/ß-catenin pathway activation, and an activator of Wnt/ß-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/ß-catenin signaling in an HIF-1-dependent manner and suggest that CALR may represent a target for BC therapy.

Hypoxia-inducible factor-dependent ADAM12 expression mediates breast cancer invasion and metastasis.

Breast cancer patients with increased expression of hypoxia-inducible factors (HIFs) in primary tumor biopsies are at increased risk of metastasis, which is the major cause of breast cancer-related mortality. The mechanisms by which intratumoral hypoxia and HIFs regulate metastasis are not fully elucidated. In this paper, we report that exposure of human breast cancer cells to hypoxia activates epidermal growth factor receptor (EGFR) signaling that is mediated by the HIF-dependent expression of a disintegrin and metalloprotease 12 (ADAM12), which mediates increased ectodomain shedding of heparin-binding EGF-like growth factor, an EGFR ligand, leading to EGFR-dependent phosphorylation of focal adhesion kinase. Inhibition of ADAM12 expression or activity decreased hypoxia-induced breast cancer cell migration and invasion in vitro, and dramatically impaired lung metastasis after orthotopic implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice.

A Label-Free Optical Biosensor Based on an Array of Microring Resonators for the Detection of Human Serum Albumin.

We introduced a label-free sensing system based on an array of microring resonators (MRRs) which was successfully employed for human serum albumin (HSA) detection. The sensing-ring surface was functionalized to immobilize anti-HSA, facilitating HSA binding. Our refractive index sensing system demonstrates high sensitivity at 168 nm/RIU and a low limit of detection (LOD) of 63.54 ng/mL, closely comparable to current HSA detection methods. These findings confirm the potential of MRRs as biocompatible sensors for HSA detection. This system holds great promise as an innovative platform for the detection of HSA, carrying significant importance in medical diagnostics.

Targeted Protein Degradation Mediated by Genetically Engineered Lysosome-Targeting Exosomes.

Protein-degrading chimeras are superior drug modalities compared to traditional protein inhibitors because of their effective therapeutic performance. So far, various targeted protein degradation strategies, including proteolysis-targeting chimeras and lysosome-targeting chimeras, have emerged as essential technologies for tackling diseases caused by abnormal protein expression. Here, we report the development and application of lysosome-targeting exosomes (LYTEXs) for the selective degradation of membrane protein targets. LYTEXs are genetically engineered exosomes expressing multivalent single-chain fragment variables, simultaneously recognizing cell-surface lysosome-targeting and to-be-degraded protein. We show that by targeting the lysosome-directing asialoglycoprotein receptor, bispecific LYTEXs can induce lysosomal degradation of membrane-associated therapeutic targets. This strategy provides a generalizable, easy-to-prepare platform for modulating surface protein expression, with the advantage of therapeutic delivery.

Selective Proteolysis of Activated Transcriptional Factor by NIR-Responsive Palindromic DNA Thalidomide Conjugate Inhibits the Canonical Smad Pathway.

Dysfunctional transcription factors that activate abnormal expressions of specific proteins are often associated with the progression of various diseases. Despite being attractive drug targets, the lack of druggable sites has dramatically hindered their drug development. The emergence of proteolysis targeting chimeras (PROTACs) has revitalized the drug development of many conventional hard-to-drug protein targets. Here, the use of a palindromic double-strand DNA thalidomide conjugate (PASTE) to selectively bind and induce proteolysis of targeted activated transcription factor (PROTAF) is reported. The selective proteolysis of the dimerized phosphorylated receptor-regulated Smad2/3 and inhibition of the canonical Smad pathway validates PASTE-mediated PROTAF. Further aptamer-guided active delivery of PASTE and near-infrared light-triggered PROTAF are demonstrated. Great potential in using PASTE for the selective degradation of the activated transcription factor is seen, providing a powerful tool for studying signaling pathways and developing precision medicines.

Single-mode interband cascade laser based on V-coupled cavity with 210†nm wavelength tuning range near 3†µm.

Interband cascade lasers (ICLs) are efficient and compact mid-infrared (3-5 µm) light sources with many applications. By enhancing the coupling coefficient and using a type-I ICL wafer, single-mode ICLs were demonstrated based on V-coupled cavity with significantly extended tuning range and with a side mode suppression ratio (SMSR) exceeding 35 dB in continuous wave operation near 3 µm. A V-coupled cavity ICL exhibited a wavelength tuning up to 67 nm at a fixed temperature, and the total tuning range exceeds 210 nm when the heat sink temperature is adjusted from 80 to 180 K. The realization of single-mode in such a wide temperature range with a tuning range exceeding 210 nm verified the advantage of V-coupled cavity ICLs for effective detection of multiple gas species. This is very different from the conventional distributed feedback (DFB) laser where the single-mode operation is restricted to a narrow temperature range, in which the match between the gain peak and the DFB grating period determined wavelength is required. Another V-coupled cavity ICL is tuned over 120 nm from 2997.56 nm to 3117.50 nm with the heat-sink temperature varied from 210 K to 240 K, over 100 K higher than the previously reported maximum operating temperature for V-coupled cavity ICLs.

4*10 Gbps WDM communication system based on a tunable V-cavity semiconductor laser.

This paper is about the V-cavity tunable semiconductor laser with a 1550 nm band used as a transmitter to build a wavelength division multiplexing (WDM) optical fiber communication link. In the experiment, a 20 km optical fiber communication link with a reasonable eye diagram and low bit error rate (BER) transmitted by 40 Gbps can be established. The experimental results show that a single laser can achieve a wavelength tuning range of 25 nm, reach 32 channels at a 100 GHz frequency interval, and the average side mode suppression ratio (SMSR) is above 39 dB. The advantages and application potential of V-cavity tunable semiconductor laser (VCL) for wavelength routing in optical communication networking are verified by experiments.

Optical-electronic hybrid Fourier convolutional neural network based on super-pixel complex-valued modulation.

An optical-electronic hybrid convolutional neural network (CNN) system is proposed and investigated for its parallel processing capability and system design robustness. It is regarded as a practical way to implement real-time optical computing. In this paper, we propose a complex-valued modulation method based on an amplitude-only liquid-crystal-on-silicon spatial light modulator and a fixed four-level diffractive optical element. A comparison of computational results of convolutions between different modulation methods in the Fourier plane shows the feasibility of the proposed complex-valued modulation method. A hybrid CNN model with one convolutional layer of multiple channels is proposed and trained electrically for different classification tasks. Our simulation results show that this model has a classification accuracy of 97.55% for MNIST, 88.81% for Fashion MNIST, and 56.16% for Cifar10, which outperforms models using only amplitude or phase modulation and is comparable to the ideal complex-valued modulation method.

Soft Sensor Modeling for 3D Transient Temperature Field of Large-Scale Aluminum Alloy Workpieces Based on Multi-Loss Consistency Optimization PINN.

Uniform temperature distribution during quenching thermal treatment is crucial for achieving exceptional mechanical and physical properties of alloy materials. Accurate and rapid prediction of the 3D transient temperature field model of large-scale aluminum alloy workpieces is key to realizing effective thermal treatment. This paper establishes a 3D transient temperature field model of large aluminum alloy workpieces and proposes a multi-loss consistency optimization-based physics-informed neural network (MCO-PINN) to realize soft sensing of the 3D temperature field model. The method is based on a MLP structure and adopts Gaussian activation functions. A surrogate model of the partial differential equation (PDE) is first constructed, and the residuals of the PDE, initial and boundary conditions, and observed data are encoded into the loss functions of the network. By establishing a Gaussian probability distribution model of each loss function and combining it with maximum likelihood estimation, the weight consistency optimization method of each loss function is then proposed to further improve the approximation ability of the model. To optimize the training speed of the network, an adaptive initial-value-eigenvector coding clustering (AIV-ECC) algorithm is finally proposed, which quickly determines the parameters of the Gaussian activation function, reduces the dependence on the initial value and improves the generalization performance of the network. Simulation and industrial experiments demonstrate that the proposed MCO-PINN can solve the 3D transient temperature field model with high precision and high time efficiency based on sparse measurements.

Modeling study on the roles of the deposition and transport of PM2.5 in air quality changes over central-eastern China.

The role of PM2.5 (particles with aerodynamic diameters ≤ 2.5 µm) deposition in air quality changes over China remains unclear. By using the three-year (2013, 2015, and 2017) simulation results of the WRF/CUACE v1.0 model from a previous work (Zhang et al., 2021), a non-linear relationship between the deposition of PM2.5 and anthropogenic emissions over central-eastern China in cold seasons as well as in different life stages of haze events was unraveled. PM2.5 deposition is spatially distributed differently from PM2.5 concentrations and anthropogenic emissions over China. The North China Plain (NCP) is typically characterized by higher anthropogenic emissions compared to southern China, such as the middle-low reaches of Yangtze River (MLYR), which includes parts of the Yangtze River Delta and the Midwest. However, PM2.5 deposition in the NCP is significantly lower than that in the MLYR region, suggesting that in addition to meteorology and emissions, lower deposition is another important factor in the increase in haze levels. Regional transport of pollution in central-eastern China acts as a moderator of pollution levels in different regions, for example by bringing pollution from the NCP to the MLYR region in cold seasons. It was found that in typical haze events the deposition flux of PM2.5 during the removal stages is substantially higher than that in accumulation stages, with most of the PM2.5 being transported southward and deposited to the MLYR and Sichuan Basin region, corresponding to a latitude range of about 24°N-31°N.

Temperature-insensitive optical sensors based on two cascaded identical microring resonators.

We demonstrate a novel, to the best of our knowledge, temperature-insensitive optical sensor based on two cascaded identical microring resonators (CIMRR) in this Letter. The structural parameters of the reference ring and sensing ring are designed to be identical. The upper cladding in the sensing windows of the two rings is removed. With different microfluidic channels, the reference ring and sensing ring are exposed to the reference solution and reagent sample, respectively. For wavelength interrogation experiments in the transmission spectrum contrast ratio and low-cost intensity interrogation experiments, the sensitivities of refractive index (RI) sensing are 3402.4 dB/RIU and 1087.3 dB/RIU, respectively, while the temperature sensitivities are as low as 0.023 dB/K and 0.0124 dB/K, respectively.

Monolithic 6 × 6 transmitter-router with simultaneous sub-nanosecond port and wavelength switching.

A monolithic 6 × 6 transmitter-router with both port and wavelength switching at sub-nanosecond speed is proposed and experimentally demonstrated. Based on an intra-cavity cyclic echelle diffraction grating router (EDGR) and semiconductor optical amplifier (SOA) arrays, each selectable output port can realize a selected multi-wavelength laser (MWL) output. The measurement results show that all 36 input-output combinations have a single-mode emission spectrum with a sidemode suppression ratio (SMSR) over 30 dB. Simultaneous switching of six laser wavelengths is achieved together with the switching of the output port by a single electrode selection. The switching time is less than 1 ns. It can offer a cost-effective solution to multi-wavelength multi-port optical transmitter-routers for fast distributed optical switching in datacenters and high-performance computers (HPCs).

Ammonium Chloride Associated Aerosol Liquid Water Enhances Haze in Delhi, India.

The interaction between water vapor and atmospheric aerosol leads to enhancement in aerosol water content, which facilitates haze development, but its concentrations, sources, and impacts remain largely unknown in polluted urban environments. Here, we show that the Indian capital, Delhi, which tops the list of polluted capital cities, also experiences the highest aerosol water yet reported worldwide. This high aerosol water promotes secondary formation of aerosols and worsens air pollution. We report that severe pollution events are commonly associated with high aerosol water which enhances light scattering and reduces visibility by 70%. Strong light scattering also suppresses the boundary layer height on winter mornings in Delhi, inhibiting dispersal of pollutants and further exacerbating morning pollution peaks. We provide evidence that ammonium chloride is the largest contributor to aerosol water in Delhi, making up 40% on average, and we highlight that regulation of chlorine-containing precursors should be considered in mitigation strategies.

Profile and outcome of receptor conversion in breast cancer metastases: a nation-wide multicenter epidemiological study.

Although receptor status including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) of the primary breast tumors was related to the prognosis of breast cancer patients, little information is yet available on whether patient management and survival are impacted by receptor conversion in breast cancer metastases. Using data from the nation-wide multicenter clinical epidemiology study of advanced breast cancer in China (NCT03047889), we report the situation of retesting ER, PR and HER2 status for breast cancer metastases and evaluate the patient management and prognostic value of receptor conversion. In total, 3295 patients were analyzed and 1583 (48.0%) patients retesting receptor status for metastasis. Discordance in one or more receptors between the primary and the metastatic biopsy was found in 37.7% of women. Patients who remained hormone receptor (HR) positive in their metastases had similar progression-free survival of first-line and second-line treatment compared to patients with HR conversion (P > .05). In multivariate analysis, patients who showed ER conversion from negative to positive had longer disease-free survival (DFS) than patients who remained negative in their metastases (hazard ratio, 2.05; 95% confidence interval [CI], 1.45-2.90; P < .001). Patients with PR remained positive and had longer DFS than patients with PR conversion from negative to positive (hazard ratio, 0.56; 95% CI, 0.38-0.83; P = .004). Patients with PR conversion have shorter overall survival than patients with PR remained positive or negative (P = .016 and P = .041, respectively). Our findings showed that the receptors' conversions were common in metastatic breast cancer, and the conversion impacted the survival.

Digital Loop-Mediated Isothermal Amplification-Based Absolute Methylation Quantification Revealed Hypermethylated DAPK1 in Cervical Cancer Patients.

The aberrant methylation of many genes has been reported to be associated with various carcinomas. Accurate detection of the methylation level could provide critical insights into the diagnostic analysis of diseases. Here, a sensitive HpaII-edited absolute droplet loop-mediated isothermal amplification (HEADLAMP) method based on methylation-sensitive restriction enzyme (MSRE) HpaII was developed for the digital quantification of DNA methylation. Methylation levels of the death-associated protein kinase 1 (DAPK1) gene that is associated with many cancers were studied using ß-actin as an internal reference. DAPK1 (2.5 pM) with 0.01% methylation (250 aM) can be detected with the conventional HpaII-edited LAMP assay. Using HEADLAMP, as low as 1% methylation level can be distinguished with an estimated limit of detection of 5 aM (ca. 3 copies/µL). Moreover, HEADLAMP can detect low levels of methylated DAPK1 in normal L-02 cells, while the conventional assay cannot. Finally, HEADLAMP was applied to the detection of DAPK1 methylation in 20 clinical tissue samples, which revealed hypermethylated DAPK1 in cervical cancer patients. We envisage potential applications of this robust, specific, and sensitive HEADLAMP assay in epigenetic studies and early clinical diagnosis.

Spindle and kinetochore­associated complex subunit 3 accelerates breast cancer cell proliferation and invasion through the regulation of Akt/Wnt/ß-catenin signaling.

PURPOSE: Spindle and kinetochore­associated complex subunit 3 (SKA3) has recently been identified as a novel regulator of carcinogenesis in multiple types of cancers. However, the function and potential regulatory mechanisms of SKA3 in breast cancer remain poorly understood. The present study was designed to gain a detailed relevance of SKA3 in breast cancer. METHODS: Expression of SKA3 in breast cancer was examined via real-time quantitative PCR, western blotting and immunohistochemistry analysis. Malignant behaviors of breast cancer cells were investigated via cell counting kit-8, cell apoptosis, and transwell invasion assays. The activity of Wnt/ß-catenin signaling was monitored via luciferase reporter assay. The tumorigenicity of breast cancer cells in vivo was assessed via xenograft tumor assay. RESULTS: SKA3 expression was elevated in breast cancer tissue and was correlated with shorter survival rates in breast cancer patients. Knockdown of SKA3 caused marked reductions in cellular proliferation and invasion in breast cancer cells, whereas SKA3 overexpression accelerated proliferation and invasion. Knockdown of SKA3 resulted in decreased Akt and glycogen synthase kinase-3ß phosphorylation, and decreased expression of active ß-catenin, which lead to the inactivation of Wnt/ß-catenin signaling. Inhibition of Akt significantly reversed the SKA3 overexpression-induced activation of Wnt/ß-catenin signaling. Inhibition of Wnt/ß-catenin signaling markedly abrogated SKA3 overexpression-induced tumor-promotion effects, while re-activation of Wnt/ß-catenin signaling significantly reversed SKA3 knockdown-mediated tumor-inhibition effects. Knockdown of SKA3 resulted in a significant decrease in breast cancer tumor formation in vivo. CONCLUSIONS: SKA3 accelerates proliferation and invasion in breast cancer through the modulation of Akt/Wnt/ß-catenin signaling.

A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape.

BACKGROUND: The diversity and plasticity behind ER+/PR-/HER2- breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. METHODS: Based on the immune-related gene expression profiles of 411 ER+/PR-/HER2- breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. RESULTS: Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. CONCLUSION: Overall, this study revealed five heterogeneous immune subtypes among ER+/PR-/HER2- breast cancer, also provided important implications for clinical translations.

Can We Reliably Identify the Pathological Outcomes of Neoadjuvant Chemotherapy in Patients with Breast Cancer? Development and Validation of a Logistic Regression Nomogram Based on Preoperative Factors.

BACKGROUND: Pathological responses of neoadjuvant chemotherapy (NCT) are associated with survival outcomes in patients with breast cancer. Previous studies constructed models using out-of-date variables to predict pathological outcomes, and lacked external validation, making them unsuitable to guide current clinical practice. OBJECTIVE: The aim of this study was to develop and validate a nomogram to predict the objective remission rate (ORR) of NCT based on pretreatment clinicopathological variables. METHODS: Data from 110 patients with breast cancer who received NCT were used to establish and calibrate a nomogram for pathological outcomes based on multivariate logistic regression. The predictive performance of this model was further validated using a second cohort of 55 patients with breast cancer. Discrimination of the prediction model was assessed using an area under the receiver operating characteristic curve (AUC), and calibration was assessed using calibration plots. The diagnostic odds ratio (DOR) was calculated to further evaluate the performance of the nomogram and determine the optimal cut-off value. RESULTS: The final multivariate regression model included age, NCT cycles, estrogen receptor, human epidermal growth factor receptor 2 (HER2), and lymphovascular invasion. A nomogram was developed as a graphical representation of the model and showed good calibration and discrimination in both sets (an AUC of 0.864 and 0.750 for the training and validation cohorts, respectively). Finally, according to the Youden index and DORs, we assigned an optimal ORR cut-off value of 0.646. CONCLUSION: We developed a nomogram to predict the ORR of NCT in patients with breast cancer. Using the nomogram, for patients who are operable and whose ORR is < 0.646, we believe that the benefits of NCT are limited and these patients can be treated directly using surgery.

SGCS: a signal reconstruction method based on Savitzky-Golaysgz filtering and compressed sensing for wavelength modulation spectroscopy.

The residual oxygen concentration in pharmaceutical glass vial variously threatens the aseptic properties of encapsulated agents. The demodulated 2nd harmonic signals in the wavelength modulation spectroscopy (WMS) detection system, the data basis of the inversion of oxygen concentration, are inevitably destroyed by various time-varying industrial noises. In this work, we propose a signal reconstruction method based on self-correcting Savitzky-Golaysgz filter and compressed sensing (namely SGCS) for the urgent signal denoising task, which is a dual-step lightweight denoising scheme. First, in order to avoid the influence of glitch noise on sparse signal reconstruction, Savitzky-Golay (S-G) filter is used to smooth the 2nd harmonic signal while retaining the change information effectively. Then, the well-tuned measurement matrix of compressed-sensing (CS) is applied to aggressively fetch the sparse principal components while bypassing most residual dynamic noises. Finally, the orthogonal matching pursuit (OMP) is used to reconstruct the 2nd harmonic signal according to sparsity constrain and the sparse principal components. Experimental results show that the performance of SGCS method is superior. Compared with other competitive methods the operation time of SGCS is the shortest. When the normalized SNR is 1, the average correct discrimination rate is 98.57%. Even if SNR reduces from 1 to 0.55, the WMS detection system still survives well, with the highest average correct discrimination rate of 89.34%.