Exploring the phosphorus-starch content balance mechanisms in maize grains using GWAS population and transcriptome data.

Examining the connection between P and starch-related signals can help elucidate the balance between nutrients and yield. This study utilized 307 diverse maize inbred lines to conduct multi-year and multi-plot trials, aiming to explore the relationship among P content, starch content, and 100-kernel weight (HKW) of mature grains. A significant negative correlation was found between P content and both starch content and HKW, while starch content showed a positive correlation with HKW. The starch granules in grains with high-P and low-starch content (HPLS) were significantly smaller compared to grains with low-P high-starch content (LPHS). Additionally, mian04185-4 (HPLS) exhibited irregular and loosely packed starch granules. A significant decrease in ZmPHOs genes expression was detected in the HPLS line ZNC442 as compared to the LPHS line SCML0849, while no expression difference was observed in AGPase encoding genes between these two lines. The down-regulated genes in ZNC442 grains were enriched in nucleotide sugar and fatty acid anabolic pathways, while up-regulated genes were enriched in the ABC transporters pathway. An accelerated breakdown of fat as the P content increased was also observed. This implied that HPLS was resulted from elevated lipid decomposition and inadequate carbon sources. The GWAS analysis identified 514 significantly associated genes, out of which 248 were differentially expressed. Zm00001d052392 was found to be significantly associated with P content/HKW, exhibiting high expression in SCML0849 but almost no expression in ZNC442. Overall, these findings suggested new approaches for achieving a P-yield balance through the manipulation of lipid metabolic pathways in grains.

Molecular insight into the initial hydration of tricalcium aluminate.

Portland cement (PC) is ubiquitously used in construction for centuries, yet the elucidation of its early-age hydration remains a challenge. Understanding the initial hydration progress of tricalcium aluminate (C3A) at molecular scale is thus crucial for tackling this challenge as it exhibits a proclivity for early-stage hydration and plays a pivotal role in structural build-up of cement colloids. Herein, we implement a series of ab-initio calculations to probe the intricate molecular interactions of C3A during its initial hydration process. The C3A surface exhibits remarkable chemical activity in promoting water dissociation, which in turn facilitates the gradual desorption of Ca ions through a metal-proton exchange reaction. The dissolution pathways and free energies of these Ca ions follow the ligand-exchange mechanism with multiple sequential reactions to form the ultimate products where Ca ions adopt fivefold or sixfold coordination. Finally, these Ca complexes reprecipitate on the remaining Al-rich layer through the interface-coupled dissolution-reprecipitation mechanism, demonstrating dynamically stable inner-sphere adsorption states. The above results are helpful in unmasking the early-age hydration of PC and advancing the rational design of cement-based materials through the bottom-up approach.

Spatiotemporal distribution and dynamics evolution of artificial intelligence development in China.

The quantified measurement and comprehensive analysis of artificial intelligence development (AIDEV) are vital for countries to form AI industrial ecology and promote the long-term development of regional AI technology. Based on the innovation ecosystems (IE) theory, this paper constructs an evaluation system to measure and analyze the spatiotemporal distribution and dynamic evolution of the AIDEV in China from 2011 to 2020. The results show that the AIDEV of China presents an overall upward trend and an obvious unbalance in the spatial distribution which is "eastern > central > western". Meanwhile, the provinces of low-level AIDEV are catching up with the high-level provinces, which leads to the regional difference of AIDEV narrowing. Moreover, the concentration and polarization phenomenon of AIDEV in China has been weakening and the AIDEV will continue to increase in the next three years. Further, there is a significantly positive spatial autocorrelation of AIDEV. Finally, high AIDEV provinces will increase the probability of surrounding provinces' AIDEV to develop. This paper expands the research stream in the field of AI research, extends the application scenarios of IE theory, and puts forward some relevant policy recommendations.

A review of biomineralization in healing concrete: Mechanism, biodiversity, and application.

Concrete is the main ingredient in construction, but it inevitably fractures during its service life, requiring a large amount of cement and aggregate for maintenance. Concrete healing through biomineralization can repair cracks and improve the durability of concrete, which is conducive to saving raw materials and reducing carbon emissions. This paper reviews the biodiversity of microorganisms capable of precipitating mineralization to repair the concrete and their mineralization ability under different conditions. To better understand the mass transfer process of precipitates, two biomineralization mechanisms, microbially-controlled mineralization and microbially-induced mineralization, have been briefly described. The application of microorganisms in the field of healing concrete, comprising passive healing and intrinsic healing, is discussed. The key insight on the interaction between cementitious materials and microorganisms is the main approach for developing novel self-healing concrete in the future to improve the corrosion resistance of concrete. At the same time, the limitations and challenges are also pointed out.

Breakthrough infection elicits hypermutated IGHV3-53/3-66 public antibodies with broad and potent neutralizing activity against SARS-CoV-2 variants including the emerging EG.5 lineages.

The rapid emergence of SARS-CoV-2 variants of concern (VOCs) calls for efforts to study broadly neutralizing antibodies elicited by infection or vaccination so as to inform the development of vaccines and antibody therapeutics with broad protection. Here, we identified two convalescents of breakthrough infection with relatively high neutralizing titers against all tested viruses. Among 50 spike-specific monoclonal antibodies (mAbs) cloned from their B cells, the top 6 neutralizing mAbs (KXD01-06) belong to previously defined IGHV3-53/3-66 public antibodies. Although most antibodies in this class are dramatically escaped by VOCs, KXD01-06 all exhibit broad neutralizing capacity, particularly KXD01-03, which neutralize SARS-CoV-2 from prototype to the emerging EG.5.1 and FL.1.5.1. Deep mutational scanning reveals that KXD01-06 can be escaped by current and prospective variants with mutations on D420, Y421, L455, F456, N460, A475 and N487. Genetic and functional analysis further indicates that the extent of somatic hypermutation is critical for the breadth of KXD01-06 and other IGHV3-53/3-66 public antibodies. Overall, the prevalence of broadly neutralizing IGHV3-53/3-66 public antibodies in these two convalescents provides rationale for novel vaccines based on this class of antibodies. Meanwhile, KXD01-06 can be developed as candidates of therapeutics against SARS-CoV-2 through further affinity maturation.

Eltrombopag directly activates BAK and induces apoptosis.

Small molecule direct BAK activators can potentially be used for the development of anti-cancer drugs or as tools to study BAK activation. The thrombopoietin receptor agonist eltrombopag (Eltro) inhibits BAX activation and BAX-mediated apoptosis. Here we report that, in contrast to its function as a BAX inhibitor, Eltro directly binds BAK but induces its activation in vitro. Moreover, Eltro induces or sensitizes BAK-dependent cell death in mouse embryonic fibroblasts (MEFs) and Jurkat cells. Chemical shift perturbation analysis by NMR indicates that Eltro binds to the BAK α4/α6/α7 groove to initiate BAK activation. Further molecular docking by HADDOCK suggests that several BAK residues, including R156, F157, and H164, play an important role in the interaction with Eltro. The introduction of an R156E mutation in the BAK α4/α6/α7 groove not only decreases Eltro binding and Eltro-induced BAK activation in vitro but also diminishes Eltro-induced apoptosis. Thus, our data suggest that Eltro directly induces BAK activation and BAK-dependent apoptosis, providing a starting point for the future development of more potent and selective direct BAK activators.

Spectral optimization of trichromatic white LEDs based on age of lighting user and application scene.

The optimization of trichromatic white light emitting diodes (LEDs) spectrum for application scenes related to the age of lighting users is proposed and demonstrated. Based on the spectral transmissivity of human eyes at different ages, the visual and non-visual responses of human eyes to different wavelengths of light, we have built the blue light hazards (BLH) and circadian action factor (CAF) related to the age of the lighting user. The BLH and CAF are used to evaluate the spectral combinations of high color rendering index (CRI) white LEDs obtained from different radiation flux ratios of red, green, and blue monochrome spectrum. The best spectra of white LEDs for lighting users at different ages in work and leisure scenes are achieved due to the optimization criterion of BLH proposed by us. This research provides a solution for intelligent health lighting design applicable to light users of different ages and application scenes.

AKT inhibition sensitizes acute leukemia cells to S63845-induced apoptosis.

The MCL1 inhibitors are undergoing clinical testing for multiple leukemia. However, because that MCL1 inhibition has on-target hematopoietic, hepatic and cardiac toxicities, there is substantial interest in finding agents can sensitize leukemia cells to the MCL1 inhibitors. Here we describe that the AKT inhibitors MK-2206 and Gsk690693 sensitize multiple leukemia cells to the MCL1 inhibitor S63845. Further experiments demonstrate that MK-2206 and Gsk690693 sensitize S63845 through the mitochondrial apoptosis pathway. Moreover, MK-2206 downregulates the anti-apoptotic protein BCLXL and induces the BH3-only pro-apoptotic protein BAD dephosphorylation and mitochondrial translocation. Knockdown of BAD significantly inhibits MK-2206-induced sensitization to S63845. Thus, our results suggest that MK-2206 sensitizes multiple leukemia cells to S63845-induced apoptosis, with the mechanisms involving BAD dephosphorylation and BCLXL downregulation.

Mitigating the impact of outliers in traffic crash analysis: A robust Bayesian regression approach with application to tunnel crash data.

Traffic crash datasets are often marred by the presence of anomalous data points, commonly referred to as outliers. These outliers can have a profound impact on the results obtained through the application of traditional methods such as logit and probit models, commonly used in the domain of traffic safety analysis, resulting in biased and unreliable estimates. To mitigate this issue, this study introduces a robust Bayesian regression approach, the robit model, which utilizes a heavy-tailed Student's t distribution to replace the link function of these thin-tailed distributions, effectively reducing the influence of outliers on the analysis. Furthermore, a sandwich algorithm based on data augmentation is proposed to enhance the estimation efficiency of posteriors. The proposed model is rigorously tested using a dataset of tunnel crashes, and the results demonstrate its efficiency, robustness, and superior performance compared to traditional methods. The study also reveals that several factors such as night and speeding have a significant impact on the injury severity of tunnel crashes. This research provides a comprehensive understanding of the outliers treatment methods in traffic safety studies and offers valuable recommendations for the development of appropriate countermeasures to effectively prevent severe injuries in tunnel crashes.

The mtDNA-STING pathway plays an important role in both navitoclax- and S63845-induced autophagy and enhances cell death.

Targeting BCL2 family proteins to induce cancer cell death has been successful in the treatment of cancer. BH3 mimetics such as ABT-737 not only induce cell death, but also activate autophagy. The molecular mechanism by which the BH3 mimetics induce autophagy is still controversial. In this study, we show that the BCL2/BCLXL/BCLw inhibitor navitoclax and the MCL1 inhibitor S63845 induce both apoptosis and autophagy in mouse embryonic fibroblasts (MEFs) and leukemia cell lines, while autophagy induced by navticlax and S63845 in leukemia cell lines requires the inhibition of caspase activities. Further experiments demonstrate that the autophagy induced by navitoclax or S63845 does not depend on Beclin 1, but downstream of Bax/Bak. Moreover, both navitoclax and S63845 treatment induce mtDNA release in MEFs, which activates STING and thereby induces autophagy, while STING KO inhibits both navitoclax- and S63845-induced autophagy. Furthermore, STING KO diminishes navitoclax- or S63845-induced apoptosis, suggesting that STING activation enhances rather than inhibits apoptosis. Thus, our findings provide new insights into the regulations of navitoclax- or S63845-induced autophagy and cell death.

How does COVID-19 pandemic affect entrepreneur anxiety? The role of threat perception and performance pressure.

The entrepreneurial firms may be more vulnerable to the COVID-19 pandemic, and the entrepreneurs of entrepreneurial firms are also threatened by the revenues decline and business failure, which vehemently affect their well-being. The mental health of the entrepreneur decides whether the entrepreneurial firms can make the right decision, which is related to the healthy development of the entrepreneurial firms. Based on the event system theory and the cognitive appraisal theory, this paper aims to explore the effect of COVID-19 pandemic on the entrepreneur anxiety, and the threat perception and performance pressure are introduced to investigate the mediating mechanism and boundary of this effect. Using the simple random sampling to obtain questionnaire survey data, 168 entrepreneurs of entrepreneurial firms have participated in the empirical study, and the research results are as follows. First, the COVID-19 pandemic significantly positively affects entrepreneur anxiety. Second, the entrepreneur threat perception plays a mediating role between the COVID-19 pandemic and the entrepreneur anxiety, which means the COVID-19 pandemic can enhance the external threat perception of entrepreneurs, and then affect the entrepreneur anxiety. Third, the positive effect of the COVID-19 pandemic on the entrepreneur anxiety is strengthened by the entrepreneur performance pressure, while the positive effect of entrepreneur threat perception on entrepreneur anxiety is weakened by the entrepreneur performance pressure. The above findings are helpful to explore the mechanism of the COVID-19 pandemic and other critical crisis events on entrepreneurs' mental health from the new perspective of cognitive appraisal theory and event system theory, filling the research gaps between the COVID-19 pandemic and entrepreneur anxiety. Besides, this study broadens the applied range of the cognitive appraisal theory and the event system theory in the fields of crisis situations and entrepreneur research, and enriches the research outputs. Furthermore, this study will help provide a new theoretical analysis insight for the related research on how the COVID-19 pandemic affects entrepreneurs' psychology, and further deepen researchers to understand the mechanism of entrepreneur anxiety under the COVID-19 pandemic, providing theoretical inspirations for reducing entrepreneur anxiety. What's more, this study finds that individual pressure can affect their cognitive appraisal, which means that future research should take the pressure influential mechanism into consideration in the process of exploring "external stimulus--cognitive appraisal--emotional response," further expanding the theoretical model of cognitive appraisal proposed from the perspective of pressure.

Development of the prediction model based on clinical-imaging omics: molecular typing and sentinel lymph node metastasis of breast cancer.

Background: Imageology uses high-throughput and automatic computing methods to transform medical image data into quantitative data with feature space, and then makes accurate quantitative analysis, extracts features and builds models, which can intuitively observe the overall features of lesions and the surrounding tissues, and provide rich invisible information. At present, the research on the imaging features of dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) to predict the molecular typing value has achieved results, but the imaging model based on DWI and DCE-magnetic resonance imaging (MRI) is not enough to predict the molecular subtypes, and the prediction value of the prediction model based on the three-dimensional volume of interest of the lesion to the four molecular subtypes of breast cancer has not been fully studied. Methods: The clinical data of 202 breast cancer patients at our hospital from October 2020 to November 2021 were collected. All patients were examined with multimodal MRI before surgery. Base on immunohistochemical recombinant Ki-67 protein (Ki-67), estrogen receptor (ER), human epidermal growth factor receptor-2 (HER-2) and progesterone receptor (PR) results, the tumors were divided into four types According to the results of the sentinel lymph node (SLN) biopsies, the patients were divided into SLN (+) and SLN (-) groups. 3-dimensional (3D) Slicer software was used to outline the region of interest (ROI), and AMni-Kinetics software was used for feature extraction. The imaging characteristics were screened using least absolute shrinkage and selection operator (LASSO)-Logistic regression model using R statistical software, and the receiver operating characteristic (ROC) curve was drawn using "pROC" software package to evaluate the prediction efficiency of the model. Results: The most efficacious model at predicting SLN (+) in breast cancer patients with different molecular subtypes and SLN metastasis was the model based on the imageological characteristics of fat inhibition, and T2-weighted imaging (T2WI), T1-weighted imaging + C (T1WI-C), and DWI combined sequences at the tumor + 2 mm periphery. AUC (sensitivity, specificity) of the validation group were 0.831 (0.856, 0.891), 0.832 (0.660, 0.877), 0.801 (0.772, 0.765), 0.904 (0.769, 0.873), and 0.819 (0.810, 0.500) respectively when the tumor was 2 mm around the tumor. Conclusions: The imaging features extracted from multi-parameter DWI, T1WI+C, and T2WI in breast cancer have certain value at predicting different molecular types and SLNs of breast cancer.

COVID-19 Pandemic and SMEs Performance Decline: The Mediating Role of Management Innovation and Organizational Resilience.

It is a major practical problem to find out a pathway for firms to quickly recover from the performance decline in the context of the COVID-19 pandemic and other sudden major crisis in the current academic circles. Based on event system theory and structural adjustment to regain fit model, this paper empirically explores the impact of the COVID-19 pandemic on SMEs performance decline and discusses the management innovation response and organizational resilience mechanism of firms by virtue of the questionnaire survey data of SMEs in Guangdong Science and Technology Park in China. The research results elucidate that the criticality and disruption of the COVID-19 pandemic will not only lead to the SMEs performance decline, but also enable SMEs to carry out management innovation. Moreover, management innovation does not directly curb the SMEs performance decline caused by the COVID-19 pandemic, but indirectly inhibit it by promoting organizational resilience. In other words, the COVID-19 pandemic will indirectly promote organizational resilience through firm management innovation, thereby curbing the SMEs performance decline. A path of management innovation response and organizational resilience to reverse the performance decline can be obtained in the study when SMEs confronting sudden major crisis. Furthermore, the study also expands the application scope of structural adjustment to regain fit model, which provides a useful reference for firm crisis response and sustainable development.

Ligand-promoted palladium-catalyzed ß-methylene C-H arylation of primary aldehydes.

The transient directing group (TDG) strategy allowed long awaited access to the direct ß-C(sp3)-H functionalization of unmasked aliphatic aldehydes via palladium catalysis. However, the current techniques are restricted to terminal methyl functionalization, limiting their structural scopes and applicability. Herein, we report the development of a direct Pd-catalyzed methylene ß-C-H arylation of linear unmasked aldehydes by using 3-amino-3-methylbutanoic acid as a TDG and 2-pyridone as an external ligand. Density functional theory calculations provided insights into the reaction mechanism and shed light on the roles of the external and transient directing ligands in the catalytic transformation.

Ab initio mechanism revealing for tricalcium silicate dissolution.

Dissolution of minerals in water is ubiquitous in nature and industry, especially for the calcium silicate species. However, the behavior of such a complex chemical reaction is still unclear at atomic level. Here, we show that the ab initio molecular dynamics and metadynamics simulations enable quantitative analyses of reaction pathways, thermodynamics and kinetics of the calcium ion dissolution from the tricalcium silicate (Ca3SiO5) surface. The calcium sites with different coordination environments lead to different reaction pathways and free energy barriers. The low free energy barriers result in that the detachment of the calcium ion is a ligand exchange and auto-catalytic process. Moreover, the water adsorption, proton exchange and diffusion of water into the surface layer accelerate the leaching of the calcium ion from the surface step by step. The discovery in this work thus would be a landmark for revealing the mechanism of tricalcium silicate hydration.

Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

Constitutive BAK/MCL1 complexes predict paclitaxel and S63845 sensitivity of ovarian cancer.

We previously found that preformed complexes of BAK with antiapoptotic BCL2 proteins predict BH3 mimetic sensitivities in lymphohematopoietic cells. These complexes have not previously been examined in solid tumors or in the context of conventional anticancer drugs. Here we show the relative amount of BAK found in preformed complexes with MCL1 or BCLXL varies across ovarian cancer cell lines and patient-derived xenografts (PDXs). Cells bearing BAK/MCL1 complexes were more sensitive to paclitaxel and the MCL1 antagonist S63845. Likewise, PDX models with BAK/MCL1 complexes were more likely to respond to paclitaxel. Mechanistically, BIM induced by low paclitaxel concentrations interacted preferentially with MCL1 and displaced MCL1-bound BAK. Further studies indicated that cells with preformed BAK/MCL1 complexes were sensitive to the paclitaxel/S63845 combination, while cells without BAK/MCL1 complexes were not. Our study suggested that the assessment of BAK/MCL1 complexes might be useful for predicting response to paclitaxel alone or in combination with BH3 mimetics.

Curcumin-loaded sandwich-like nanofibrous membrane prepared by electrospinning technology as wound dressing for accelerate wound healing.

Wound healing is a complicated process constituted of four successive physiological stages involving wound bleeding, inflammatory response, cell proliferation and tissue remodeling. During this period, bacteria can easily infect the wound. Therefore, we prepared a novel curcumin-loaded sandwich-like nanofibrous membrane (CSNM) using sequential electrospinning for the hemostasis, antibacterial and accelerate wound healing. The morphology of the nanofibrous membrane was analyzed by SEM. In addition, the water absorption capacity, water vapor transmission rate, water contact-angle, and in vitro drug release were all tested. Then in vitro and in vivo hemostatic experiments demonstrated that CSNM has a good hemostatic effect. Antioxidant effect was assessed by the DPPH radical scavenging method and CSNM presented a high antioxidant activity. Additionally, CSNM demonstrated excellent antibacterial activity by the disk diffusion method. Furthermore, the rat dorsal skin defects model revealed that the CSNM distinctly induced the granulation tissue grew, collagen deposition and epithelial tissue remodeling. Meanwhile, the results of the immunohistochemical staining showed that the CSNM can facilitate the expression of CD31 and TGF-ß in the early stage of the wound, thereby accelerating wound healing. In general, this study proved that the multifunctional CSNM has great potential as wound dressing in wound healing.

A novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers for postoperative rapid hemostasis and prevention of tumor recurrence.

Surgical resection of the tumor remains the preferred treatment for most solid tumors at an early stage, but surgical treatment often leads to massive bleeding and residual tumor cells. Therefore, a novel alginate/gelatin sponge combined with curcumin-loaded electrospun fibers (CFAGS) for rapid hemostasis and prevention of tumor recurrence was prepared by using an electrospinning and interpenetrating polymer network (IPN) strategy. The present results show that alginate/gelatin sponge display excellent hemostatic properties and possess more advantages than commercial gelatin hemostasis sponge. More importantly, CFAGS could control the release of curcumin, inducing curcumin to accumulate at the surgical site of the tumor, thereby inhibiting local tumor recurrence in the subcutaneous postoperative recurrence model. In addition, the sponge was safe to implant in the body and did not cause toxicity to normal tissues and organs. This approach represents a new strategy to implant a dual functional sponge at the postoperative site as an adjuvant to the surgical treatment of cancer.