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DNA double-strand breaks (DSBs) are functionally linked to genomic instability in spermatocytes and to male infertility. The heavy metal cadmium (Cd) is known to induce DNA damage in spermatocytes by unknown mechanisms. Here, we showed that Cd ions impaired the canonical non-homologous end-joining (NHEJ) repair pathway, but not the homologous recombination (HR) repair pathway, through stimulation of Ser2056 and Thr2609 phosphorylation of DNA-PKcs at DSB sites. Hyper-phosphorylation of DNA-PKcs led to its premature dissociation from DNA ends and the Ku complex, preventing recruitment of processing enzymes and further ligation of DNA ends. Specifically, this cascade was initiated by the loss of PP5 phosphatase activity, which results from the dissociation of PP5 from its activating ions (Mn), that is antagonized by Cd ions through a competitive mechanism. In accordance, in a mouse model Cd-induced genomic instability and consequential male reproductive dysfunction were effectively reversed by a high dosage of Mn ions. Together, our findings corroborate a protein phosphorylation-mediated genomic instability pathway in spermatocytes that is triggered by exchange of heavy metal ions.

Background The diagnostic effectiveness of traditional imaging techniques is insufficient to assess the response of lymph nodes (LNs) to neoadjuvant chemotherapy (NAC), especially for pathological complete response (pCR). A radiomics model based on computed tomography (CT) could be helpful. Patients and Methods Prospective consecutive breast cancer patients with positive axillary LNs initially were enrolled, who received NAC prior to surgery. Chest contrast-enhanced thin-slice CT scan was performed both before and after the NAC (recorded as the first and the second CT respectively), and on both of them, the target metastatic axillary LN was identified and demarcated layer by layer. Using pyradiomics-based software that was independently created, radiomics features were retrieved. A pairwise machine learning workflow based on Sklearn (https://scikit-learn.org/) and FeAture Explorer was created to increase diagnostic effectiveness. An effective pairwise auto encoder model was developed by the improvement of data normalization, dimensionality reduction, and features screening scheme as well as the comparison of the prediction effectiveness of the various classifiers, Results A total of 138 patients were enrolled, and 77 (58.7%) in the overall group achieved pCR of LN after NAC. Nine radiomics features were finally chosen for modeling. The AUCs of the training group, validation group, and test group were 0.944 (0.919-0.965), 0.962 (0.937-0.985), and 1.000 (1.000-1.000), respectively, and the corresponding accuracies were 0.891, 0.912, and 1.000. Conclusion The pCR of axillary LNs in breast cancer following NAC can be precisely predicted using thin-sliced enhanced chest CT-based radiomics.

Herein, a straightforward route for dual α,β-C(sp3)–H functionalized cyclic N-aryl amines using a combination of electrocatalysis and iron catalysis is disclosed, setting the stage for the challenging multiple site selective C–H functionalization.

OBJECTIVE: To assess the safety and effectiveness of intravascular lithotripsy (IVL) treatment for de novo coronary lesion involving severely calcified vessels in a Chinese population. METHODS: The Clinical Trial of the ShOckwave Coronary IVL System Used to Treat CalcIfied Coronary ArtEries (SOLSTICE) was a prospective, single-arm, multicentre trial. According to the inclusion criteria, patients with severely calcified lesions were enrolled in the study. IVL was used to perform calcium modification prior to stent implantation. The primary safety endpoint was freedom from major adverse cardiac events (MACEs) at 30 days. The primary effectiveness endpoint was procedural success, defined as successful stent delivery with residual stenosis < 50% by core lab assessment without in-hospital MACEs. The morphological changes of calcium modification were assessed by optical coherence tomography (OCT) before and after IVL treatment. RESULTS: Patients (n = 20) were enrolled at three sites in China. Severe calcification by core lab assessment was present in all lesions, with a mean calcium angle and thickness of 300 ± 51° and 0.99 ± 0.12 mm (by OCT), respectively. The 30-day MACE rate was 5%. Both primary safety and effectiveness endpoints were achieved in 95% of patients. The final in-stent diameter stenosis was 13.1% ± 5.7% with no patient had a residual stenosis < 50% after stenting. No serious angiographic complications (severe dissection grade D or worse, perforation, abrupt closure, slow flow/no-reflow) observed at any time during the procedure. OCT imaging demonstrated visible multiplane calcium fracture in 80% of lesions with a mean stent expansion of 95.62% ± 13.33% at the site of maximum calcification and minimum stent area (MSA) of 5.34 ± 1.64 mm(2). CONCLUSIONS: The initial coronary IVL experience for Chinese operators resulted in high procedural success and low angiographic complications consistent with prior IVL studies, reflecting the relative ease of use of IVL technology.

This study aimed to investigate the effect of dexamethasone (DEX) on chemotaxis and phagocytic activity of neutrophils for spermatozoa and semen quality of preserved boar semen. The different concentrations of dexamethasone were added to boar semen dilutions to detect its effects on the chemotaxis of neutrophils and phagocytosis of neutrophils and sperm motility sperm malformation rate, plasma membrane integrity, mitochondrial activity, and spermatozoa motility parameters. The study results showed that the experimental groups of DEX significantly inhibited the phagocytosis and chemotaxis of PMNs for spermatozoa. With the increased concentration of DEX, there was an inhibition effect on PMNs activity. In addition, under 17 °C storage conditions, the addition of DEX 1 × 10

One of the greatest challenges in integrated circuit design is the repeated executions of computationally expensive SPICE simulations, particularly when highly complex chip testing/verification is involved. Recently, pseudo-transient analysis (PTA) has shown to be one of the most promising continuation SPICE solvers. However, the PTA efficiency is highly influenced by the inserted pseudo-parameters. In this work, we proposed BoA-PTA, a Bayesian optimization accelerated PTA that can substantially accelerate simulations and improve convergence performance without introducing extra errors. Furthermore, our method does not require any pre-computation data or offline training. The acceleration framework can either speed up ongoing, repeated simulations (e.g., Monte-Carlo simulations) immediately or improve new simulations of completely different circuits. BoA-PTA is equipped with cutting-edge machine learning techniques, such as deep learning, Gaussian process, Bayesian optimization, non-stationary monotonic transformation, and variational inference via reparameterization. We assess BoA-PTA in 43 benchmark circuits and real industrial circuits against other SOTA methods and demonstrate an average of 1.5x (maximum 3.5x) for the benchmark circuits and up to 250x speedup for the industrial circuit designs over the original CEPTA without sacrificing any accuracy.

Hepatitis C virus (HCV) infection remains a serious public health burden around the world. So far there is no effective vaccine against this virus. Neutralizing antibody (NAb) responses to the epitopes within HCV E1 and E2 proteins are related to the resolution of hepatitis C infection. E. coli heat-labile enterotoxin B subunit (LTB) has been described as potent immunity adjuvants. In this study, we constructed recombinant pET vectors: pET-R9-Bp (B cell polyepitopes) expressing 7 epitopes from HCV E1 and E2 proteins including R9 (E2

The specific objective of this study was to evaluate the effects of atmospheric pressure plasma (APP) in the treatment of experimental periodontitis in Beagle dogs.The APP jet was diagnosed using optical emission spectroscopy and laser-induced fluorescence spectroscopy. Six Beagles received stainless steel ligatures to establish experimental periodontitis model. The teeth in the control group were subjected to conventional root surface debridement (RSD) and chlorhexidine irrigation. The APP group also started with RSD and was then subjected to plasma irradiation. Clinical analyses including plaque index, modified sulcus bleeding index, pocket depth and attachment loss (AL), as well as cone-beam computed tomography (CBCT) analysis, were performed at baseline, 4th week, 8th week and 12th week after treatment.The results showed that typical reactive oxygen and nitrogen species were found in the full spectrum and the gas temperature of APP was close to room temperature. The highest concentrations of hydroxide and oxygen were obtained at 5 mm away from the nozzle. In both groups, all values in clinical examinations were significantly lower (P0.05) at 12th week after treatment than those at baseline. At the 12th week, the AL in clinical examinations and the bone loss in CBCT images in the APP group were significantly lower than those in the control group (P0.05). The hematoxylin-eosin staining showed more renascent alveolar bone in the APP group than in the control group.These findings suggested that APP has profound potential for use as an adjunct approach for periodontitis treatment.

A sensitive and accurate LC-MS/MS method was developed and validated for the simultaneous quantification of rivaroxaban (RIV) and sitagliptin (SIT) in rat plasma using apixaban as internal standard (IS). An Agilent Eclipse plus C18 column (2.1 × 100 mm, 3.5 µm, Agilent) was used for chromatographic separation with isocratic elution. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 436.8→144.9 for RIV, m/z 407.7→173.8 for SIT, m/z 459.8→442.8 for IS. The procedure of method validation included selectivity, linearity, precision, accuracy, matrix effect, extraction recovery and stability were conducted according to the guidelines of EMA and FDA. The results indicated that no obvious drug-drug interactions occurred might be owing to their differences in metabolic pathways.

In order to prepare cement concrete with high mechanical properties and durability, nano-stainless steel powder reactive powder cement concrete (RPC) was manufactured. The dosage of nano-stainless steel powder ranged from 0% to 1.2% by the total volume of the RPC. In this study, the compressive and flexural strengths of the RPC with nano-stainless steel powder were determined, the dry shrinkage rate of the RPC was tested and the electrical resistance and alternating current (AC) impedance spectrum of the RPC were measured; moreover, the corresponding strain-sensing properties were investigated, and the scanning electron microscope (SEM) was used for observing the microstructures of the RPC. The results showed that the RPC with 1.0% nano-stainless steel powder exhibited the threshold values of the mechanical strengths. The maximum flexural strength and compressive strength were 16.1% and 14.2% higher than the minimum values. The addition of the nano-stainless steel powders reduced the dry shrinkage rate by 12.1%–39.8%. The electrical resistance of the RPC decreased in the form of the cubic function with the volume fraction of the stainless steel powders. The 1.0% nano-stainless steel powder was the threshold value for the electrical resistance and piezoresistive performance. The relationship between the electrical reactance and electrical resistance fitted well with the quadratic function. As obtained from the SEM results, the addition of the nano-stainless steel powder could effectively improve the compactness of the hydration products.

In order to achieve the emission peak and carbon neutrality ("30·60" goals), personal carbon trading may be included in China's carbon trading market in the future, based on the corporate-level carbon trading that is already in place. It will be an effective solution to reduce carbon emissions from the consumption side and can be used as a supplement to the corporate carbon trading mechanism and carbon tax. This study constructs a personal carbon trading system based on the fundamental realities of China, which includes four attributes: carbon quota acquisition, trading partner selection, low-carbon behavior offset mechanism, and value preservation mode. Through questionnaire survey and choice experiment, the logit model is used to analyze the influence of the four attributes upon the individual willingness to participate in personal carbon trading and the heterogeneity of the public on personal carbon trading in the context of carbon neutrality policy. The study found that the influence of the attributes on the willingness to participate was ranked as follows: carbon quota acquisition value preservation mode low-carbon behavior offset mechanism trading partner selection. The level of knowledge about carbon neutrality and salary will have a significant positive impact on the attribute-level preference of personal carbon trading. Finally, suggestions are made for designing, applying, and promoting personal carbon trading mechanisms to improve the public's willingness to participate in personal carbon trading and perfect the construction of carbon trading systems at the consumption side. The take-home message of the study is that a well-established personal carbon trading mechanism is an effective solution for reducing greenhouse gas emissions.

The left-lateral strike-slip Xiaojiang fault is an important tectonic boundary between Sichuan–Yunnan diamond block and the Yangtze block, which accommodated several M > 7.0 damaging earthquakes in the past ∼500 yr, as well as intense tectonic deformation. However, the seismogenesis of its middle-northern section are not well understood due to the lack of dense stations. In this study, we analyze one year of continuous seismic records from November 2019 to November 2020, which are recorded at a recently deployed dense seismic array. We build a high-precision earthquake catalog for the region using our recently developed machine learning-based earthquake location workflow (LOC-FLOW), which consists of machine learning phase picking, phase association, velocity model updating, and station correction, absolute location, and double-difference relative location. We then adopt a double-difference tomography method (tomoDD) to refine locations of 16,000 events and build a high-resolution 3D velocity model using both machine learning differential times and cross-correlation differential times. The seismicity distribution not only delineates detailed geometry of the main fault system but also characterizes several branch faults, including two echelon subfaults crossing the north–south-striking main fault. The velocity model shows strong lateral heterogeneities and exhibits a clear relationship to the seismicity distribution: the boundary of high- and low-velocity regions or high-velocity regions above low-velocity bodies accommodate the majority of earthquakes. The variation of the constructed 3D velocity model can be well explained by geological and tectonic settings of the region. In addition, we identify two seismic gaps, which accumulate stress and imply the potential of hosting future moderate-to-large earthquakes. Our study demonstrates, with the aid of LOC-FLOW and tomoDD, machine learning-based phase picks lead to promising performance in constraining high-precision earthquake catalogs and constructing high-resolution velocity models. Machine learning-based tools are becoming the next generation of routine earthquake analysis.

PurposeCurrent policies and research on carbon emissions focus on operational emission but overlook the importance of embodied and user-transport emissions in residential buildings. This study built a comprehensive framework to assess the impact of life-cycle carbon emissions on different in-building open public spaces (open roof, open vertical garden, and open ground floor) in affordable housing.Design/methodology/approachA parametric model of a typical affordable housing building in Shanghai, China was constructed and 36 variations of open public spaces studied. Embodied, operational, and user-transport carbon emissions were quantified over 50 years.FindingsThe results show that the life-cycle carbon emissions decrease with the application of the open public space. In addition, the paper found that the carbon reduction due to user transport is seven times higher than the carbon increment due to construction and over long-term operation.Originality/valueThis paper provides quantitative evidence for carbon emissions and in-building open public spaces, and the authors suggest taking multiple aspects into account in addition to the structure of the building is crucial to sustainable building development.

Background: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer’s disease (AD) patients. Objective: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20–30% among the dementia society, were still elusive. Methods: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. Results: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-β pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. Conclusion: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.

Functionalized cyclic amines are essential structural motifs in synthetic chemistry and pharmaceutical chemistry, and Shono-type oxidation is a well-developed electrochemical approach for the synthesis of α- amines. In sharp contrast, electrochemically driven direct β-C(sp3)–H functionalization of amines has been far proven elusive. Herein, we outline the recent advances in this field and highlight our group’s effort to achieve electrochemical β-C(sp3)–H functionalization assisted by ferrocene as molecular electrocatalyst under mild conditions.1 Introduction2 Case studies of α-Functionalization (Shono-Type Oxidation)3 Electrochemical β-C(sp3)–H Acylation4 Conclusion

To achieve carbon neutrality and carbon reduction goals, China needs to consider industrial structure and trade. This study aims to test the validity of environmental Kuznets curve (EKC) hypothesis at the industry level in China and study the different impact of Sino-US trade in intermediate goods and trade in final goods on China's environment. To do so, we used the annual data of China's 25 sectors in 1990-2015 and classified 25 sectors into three main industries. Based on the Stochastic Impacts by Regression on Population, Affluence and Technology framework, we investigated the validity of EKC hypothesis and the driving factors of greenhouse gas (GHG) emissions. The results show that (1) EKC hypothesis is verified for the country and the tertiary industry. (2) Compared with the primary industry and the secondary industry, the economic growth of the tertiary industry brings less GHG emissions. (3) Intermediate goods exported to all sectors in the USA will increase GHG emissions in the country and the three main industries, but final goods exported to consumers in the USA will reduce GHG emissions except the tertiary industry. From our results, the EKC hypothesis is a suitable model for environmental policy in tertiary industry, but it does not apply to the primary industry and the secondary industry. Environmental policy in the primary industry and the secondary industry needs to focus on reducing energy intensity. In the case of exports to the USA, intermediate goods pollute the environment, while final improve the environment. Thus, China needs to increase controls on exports of intermediate goods with low added value and high pollution and gradually shift to the production of environmentally friendly final goods.

The ever-increasing networks and quantity of seismic data drive the need for seamless and automatic workflows for rapid and accurate earthquake detection and location. In recent years, machine learning (ML)-based pickers have achieved remarkable accuracy and efficiency with generalization, and thus can significantly improve the earthquake location accuracy of previously developed sequential location methods. However, the inconsistent input or output (I/O) formats between multiple packages often limit their cross application. To reduce format barriers, we incorporated a widely used ML phase picker—PhaseNet—with several popular earthquake location methods and developed a “hands-free” end-to-end ML-based location workflow (named LOC-FLOW), which can be applied directly to continuous waveforms and build high-precision earthquake catalogs at local and regional scales. The renovated open-source package assembles several sequential algorithms including seismic first-arrival picking (PhaseNet and STA/LTA), phase association (REAL), absolute location (VELEST and HYPOINVERSE), and double-difference relative location (hypoDD and GrowClust). We provided different location strategies and I/O interfaces for format conversion to form a seamless earthquake location workflow. Different algorithms can be flexibly selected and/or combined. As an example, we apply LOC-FLOW to the 28 September 2004 Mw 6.0 Parkfield, California, earthquake sequence. LOC-FLOW accomplished seismic phase picking, association, velocity model updating, station correction, absolute location, and double-difference relocation for 16-day continuous seismic data. We detected and located 3.7 times (i.e., 4357) as many as earthquakes with cross-correlation double-difference locations from the Northern California Earthquake Data Center. Our study demonstrates that LOC-FLOW is capable of building high-precision earthquake catalogs efficiently and seamlessly from continuous seismic data.

Background: Recent studies have revealed that atrial fibrillation (AF) patients have a high risk of developing cognitive impairment, vascular dementia, and Alzheimer’s disease (AD). Some reports suggest that the application of oral anticoagulant with an appropriate dose may have a preventive effect on AD. However, which oral anticoagulant drug is more appropriate for preventing AD and the underlying mechanism(s) is still unknown. Objective: The aim of the present study was to assess the treatment effect of rivaroxaban administration as well as investigate the roles of PAR-1 and PAR-2 in the AD + CAA mice model. Methods: In the present study, we compared a traditional oral anticoagulant, warfarin, and a direct oral anticoagulant (DOAC), rivaroxaban, via long-term administration to an AD with cerebral amyloid angiopathy (CAA) mice model. Results: Rivaroxaban treatment attenuated neuroinflammation, blood-brain barrier dysfunction, memory deficits, and amyloid-β deposition through PAR-1/PAR-2 inhibition in the AD + CAA mice model compared with warfarin and no-treatment groups. Conclusion: The present study demonstrates that rivaroxaban can attenuate AD progress and can be a potential choice to prevent AD.

Recent studies have experimentally shown that we can achieve in non-Euclidean metric space effective and efficient graph embedding, which aims to obtain the vertices' representations reflecting the graph's structure in the metric space. Specifically, graph embedding in hyperbolic space has experimentally succeeded in embedding graphs with hierarchical-tree structure, e.g., data in natural languages, social networks, and knowledge bases. However, recent theoretical analyses have shown a much higher upper bound on non-Euclidean graph embedding's generalization error than Euclidean one's, where a high generalization error indicates that the incompleteness and noise in the data can significantly damage learning performance. It implies that the existing bound cannot guarantee the success of graph embedding in non-Euclidean metric space in a practical training data size, which can prevent non-Euclidean graph embedding's application in real problems. This paper provides a novel upper bound of graph embedding's generalization error by evaluating the local Rademacher complexity of the model as a function set of the distances of representation couples. Our bound clarifies that the performance of graph embedding in non-Euclidean metric space, including hyperbolic space, is better than the existing upper bounds suggest. Specifically, our new upper bound is polynomial in the metric space's geometric radius $R$ and can be $O(\frac{1}{S})$ at the fastest, where $S$ is the training data size. Our bound is significantly tighter and faster than the existing one, which can be exponential to $R$ and $O(\frac{1}{\sqrt{S}})$ at the fastest. Specific calculations on example cases show that graph embedding in non-Euclidean metric space can outperform that in Euclidean space with much smaller training data than the existing bound has suggested.

Actinomorphic flowers usually orient vertically (relative to the horizon) and possess symmetric nectar guides, while zygomorphic flowers often face horizontally and have asymmetric nectar guides, indicating that floral symmetry, floral orientation, and nectar guide patterning are correlated. The origin of floral zygomorphy is dependent on the dorsoventrally asymmetric expression of CYCLOIDEA (CYC)-like genes. However, how horizontal orientation and asymmetric nectar guides are achieved remains poorly understood. Here, we selected Chirita pumila (Gesneriaceae) as a model plant to explore the molecular bases for these traits. By analyzing gene expression patterns, protein–DNA and protein–protein interactions, and encoded protein functions, we identified multiple roles and functional divergence of 2 CYC-like genes, i.e. CpCYC1 and CpCYC2, in controlling floral symmetry, floral orientation, and nectar guide patterning. CpCYC1 positively regulates its own expression, whereas CpCYC2 does not regulate itself. In addition, CpCYC2 upregulates CpCYC1, while CpCYC1 downregulates CpCYC2. This asymmetric auto-regulation and cross-regulation mechanism might explain the high expression levels of only 1 of these genes. We show that CpCYC1 and CpCYC2 determine asymmetric nectar guide formation, likely by directly repressing the flavonoid synthesis-related gene CpF3′5′H. We further suggest that CYC-like genes play multiple conserved roles in Gesneriaceae. These findings shed light on the repeated origins of zygomorphic flowers in angiosperms.

Dairy foods are crucial for adequate calcium intake in young children, but scarce data are available on the effects of formula milk on bone acquisition. This cluster-randomized controlled trial investigated the effects of the supplementation of formula milk on bone health in rural children accustomed to a low-calcium diet between September 2021 and September 2022. We recruited 196 healthy children aged 4–6 years from two kindergartens in Huining County, Northwest China. A class-based randomization was used to assign them to receive 60 g of formula milk powder containing 720 mg calcium and 4.5 µg vitamin D or 20–30 g of bread per day for 12 months, respectively. Bone mineral density (BMD) and bone mineral content (BMC) at the left forearm and calcaneus, bone biomarkers, bone-related hormones/growth factors, and body measures were determined at baseline, 6, and 12 months. A total of 174 children completed the trial and were included in the analysis. Compared with the control group, formula milk intervention showed significant extra increments in BMD (3.77% and 6.66%) and BMC (4.55% and 5.76%) at the left forearm at 6th and 12th months post-intervention (all p < 0.001), respectively. Similar trends were observed in BMD (2.83%) and BMC (2.38%) in the left calcaneus at 6 months (p < 0.05). The milk intervention (vs. control) also showed significant changes in the serum concentrations of osteocalcin level (−7.59%, p = 0.012), 25-hydroxy-vitamin-D (+5.54%, p = 0.001), parathyroid hormone concentration (−15.22%, p = 0.003), and insulin-like growth factor 1 (+8.36%, p = 0.014). The percentage increases in height were 0.34%, 0.45%, and 0.42% higher in the milk group than in the control group after 3-, 6-, and 9-month intervention, respectively (p < 0.05). In summary, formula milk supplementation enhances bone acquisition at the left forearm in young Chinese children.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, while its possible role in the secondary injury after TBI remain obscure. In the present study, we observed thatthe level of plasma irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes ofTBI patients. Knockout of FNDC5increased the lesion volume and exacerbated apoptosis and neurological deficitsafter TBI in mice, whileFNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5failed to attenuateTBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

The in-fall of meteorites and interstellar dust particles during the Hadean–Archean heavy bombardment may have provided the early Earth with various reduced oxidation state phosphorus compounds and minerals, including phosphite (HPO32−)([Pi(III)]). The ion phosphite ([Pi(III)])has been postulated to be ubiquitous on the early Earth and consequently could have played a role in the emergence of organophosphorus compounds and other prebiotically relevant P species such as condensed P compounds, e.g., pyrophosphite ([PPi(III)]) and isohypophosphate ([PPi(III–V)]). In the present study, we show that phosphite ([Pi(III)]) oxidizes under mild heating conditions (e.g., wet–dry cycles and a prebiotic scenario mimicking a mildly hot-evaporating/drying pool on the early Earth at 78–83 °C) in the presence of urea and other additives, resulting in changes to orthophosphate ([Pi(V)]) alongside the formation of reactive condensed P compounds (e.g., pyrophosphite ([PPi(III)]) and isohypophosphate ([PPi(III–V)])) through a one-pot mechanism. Additionally, we also show that phosphite ([Pi(III)]) and the condensed P compounds readily react with organics (nucleosides and organic alcohol) to form organophosphorus compounds.

Purpose: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC).Experimental Design: MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways.Results: MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression–related signaling pathways including JNK, NFκB, and toll-like receptors were repressed by MAP4K4 downregulation.Conclusions: MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance. Clin Cancer Res; 17(4); 1–11. ©2010 AACR.

Supplementary Figures S1-S2; Supplementary Tables S1-S4.

A novel and sensitive quantum dots-molecularly imprinted polymer (MIPs-capped ZnS:Mn QDs) was synthesized for the rapid and specific recognition of teflubenzuron (TBZ) in water samples. Based on the fluorescence quenching via template analytes(TBZ) rebinding into the specific recognition cavities in the polymer, which allowed the TBZ to be sensed optically. Under optimal conditions, MIPs-capped ZnS:Mn QDs was applied to detection of TBZ, and a linear relationship was obtained over the concentration range 0-100mg/L with a correlation coefficient of 0.9981. Four structurally similar compounds were used for the selectivity test of MIPs-capped ZnS:Mn QDs. It was observed that the obtained composites can selectively rebind the template molecules(TBZ). In addition, MIPs-capped ZnS:Mn QDs were successfully applied to the detection of TBZ in cabbage samples. The recovery is between 90.35 and 97.09% with relative standard deviations in the range of 2.45–3.17%. The polymer developed in this work has the advantages of simple preparation and processing, fast response, low toxicity and good optical stability, which is very promising for the detection of TBZ.

Phosphate minerals such as those in the apatite group tend to be the dominant forms of phosphorus in minerals on the Earth’s surface. Phosphate can be reduced to phosphides during high-energy events, such as lightning and impacts. Here we show that, in addition to formation of metal phosphides, a new compound was formed by lightning in a fulgurite from New Port Richey, Florida, USA. A calcium phosphite material, ideally CaHPO3, was found in spherules mainly consisting of iron silicides that formed by lightning-induced fusion of sand around a tree root. This phosphite material bears a phosphorus oxidation state intermediate of that of phosphides and phosphates in a geologic sample and implicates phosphites as being potentially relevant to other high-energy events where phosphorus may partially change its redox state, and material similar to this phosphite may also be the source of phosphite that makes up part of the phosphorus biogeochemical cycle.

The dense quantum entanglement distribution is the basis for practical quantum communication, quantum networks and distributed quantum computation. To make entanglement distribution processes stable enough for practical and large-scale applications, it is necessary to perform them with the integrated pattern. Here, we first integrate a dense wavelength-division demultiplexing system and unbalanced Mach-Zehnder interferometers on one large-scale photonic chip and demonstrate the multi-channel wavelength multiplexing entanglement distribution among distributed photonic chips. Specifically, we use one chip as a sender to produce high-performance and wideband quantum photon pairs, which are then sent to two receiver chips through 1-km standard optical fibers. The receiver chip includes a dense wavelength-division demultiplexing system and unbalanced Mach-Zehnder interferometers and realizes multi-wavelength-channel energy-time entanglement generation and analysis. High quantum interference visibilities prove the effectiveness of the multi-chip system. Our work paves the way for practical entanglement-based quantum key distribution and quantum networks.

In earlier studies, objective techniques have been used to determine the contribution of tropical cyclones to precipitation (TCP) in a region, where the Tropical cyclone Precipitation Event (TPE) and the Regional Heavy Precipitation Events (RHPEs) are defined and investigated. In this study, TPE and RHPEs are combined to determine the Typhoon Regional Heavy Precipitation Events (TRHPEs), which is employed to evaluate the contribution of tropical cyclones to regional extreme precipitation events. Based on the Objective Identification Technique for Regional Extreme Events (OITREE) and the Objective Synoptic Analysis Technique (OSAT) to define TPE, temporal and spatial overlap indices are developed to identify the combined events as TRHPE. With daily precipitation data and TC best-track data over the western North Pacific from 1960 to 2018, 86 TRHPEs have been identified. TRHPEs contribute as much as 20% of the RHPEs, but 100% of events with extreme individual precipitation intensities. The major TRHPEs continued for approximately a week after tropical cyclone landfall, indicating a role of post landfall precipitation. The frequency and extreme intensity of TRHPEs display increasing trends, consistent with an observed positive trend in the mean intensity of TPEs as measured by the number of daily station precipitation observations exceeding 100 mm and 250 mm. More frequent landfalling Southeast and South China TCs induced more serious impacts in coastal areas in the Southeast and the South during 1990–2018 than 1960–89. The roles of cyclone translation speed and “shifts” in cyclone tracks are examined as possible explanations for the temporal trends.