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Byline: Song. Hang, Xu. Kai-Feng, Zhang. Chen-Xi, Zhang. Xiao, Zhang. Zhi-Qiao Three cases of tuberous sclerosis complex (TSC)-associated retinal astrocytic hamartomas (RAH) complicated with vitreous hemorrhage were presented in this [...]

BRCA1, a breast cancer susceptibility gene, has emerged as a central mediator that brings together multiple signaling complexes in response to DNA damage. The A, B, and C complexes of BRCA1, which are formed based on their phosphorylation-dependent interactions with the BRCA1-C-terminal domains, contribute to the roles of BRCA1 in DNA repair and cell cycle checkpoint control. However, their functions in DNA damage response remain to be fully appreciated. Specifically, there has been no systematic investigation of the roles of BRCA1-A, -B, and -C complexes in the regulation of BRCA1 localization and functions, in part because of cellular lethality associated with loss of CtIP protein, which is an essential component in BRCA1-C complex. To systematically investigate the functions of these complexes in DNA damage response, we depleted a key component in each of these complexes. We used the degradation tag system to inducibly deplete endogenous CtIP and obtained a series of RAP80/FANCJ/CtIP single-, double-, and triple-knockout cells. We showed that loss of BRCA1-B/FANCJ and BRCA1-C/CtIP, but not BRCA1-A/RAP80, resulted in reduced cell proliferation and increased sensitivity to DNA damage. BRCA1-C/CtIP and BRCA1-A/RAP80 were involved in BRCA1 recruitment to sites of DNA damage. However, BRCA1-A/RAP80 was not essential for damage-induced BRCA1 localization. Instead, RAP80/H2AX and CtIP have redundant roles in BRCA1 recruitment. Altogether, our systematic analysis uncovers functional differences between BRCA1-A, -B, and -C complexes and provides new insights into the roles of these BRCA1-associated protein complexes in DNA damage response and DNA repair.

Objective: The mechanical properties of corneal tissues play a crucial role in determining corneal shape and have significant implications in vision care. This study aimed to address the challenge of obtaining accurate in vivo data for the human cornea. Methods: We have developed a high-frequency optical coherence elastography (OCE) technique using shear-like antisymmetric (A0)-mode Lamb waves at frequencies above 10 kHz. Results: By incorporating an anisotropic, nonlinear constitutive model and utilizing the acoustoelastic theory, we gained quantitative insights into the influence of corneal tension on wave speeds and elastic moduli. Our study revealed significant spatial variations in the shear modulus of the corneal stroma on healthy subjects for the first time. Over an age span from 21 to 34 (N = 6), the central corneas exhibited a mean shear modulus of 87 kPa, while the corneal periphery showed a significant decrease to 44 kPa. The central cornea's shear modulus decreases with age with a slope of −19 +/− 8 kPa per decade, whereas the periphery showed non-significant age dependence. The limbus demonstrated an increased shear modulus exceeding 100 kPa. We obtained wave displacement profiles that are consistent with highly anisotropic corneal tissues. Conclusion: Our approach enabled precise measurement of corneal tissue elastic moduli in situ with high precision (<7%) and high spatial resolution (<1 mm). Our results revealed significant stiffness variation from the central to peripheral corneas. Significance: The high-frequency OCE technique holds promise for biomechanical evaluation in clinical settings, providing valuable information for refractive surgeries, degenerative disorder diagnoses, and intraocular pressure assessments.

Methoxyeugenol is a phenylpropene compound derived from plants and has various bioactivities. The chemical synthesis of methoxyeugenol is accompanied by pollution issues, whereas extraction from plants is associated with problems such as low yield and high cost. The production of methoxyeugenol can be effectively addressed through an enzymatic approach. In this study, the acyltransferase genes of Euphorbia lathyrisL. were screened by homologous alignment of the transcriptome data of E. lathyrisin the late growth stage and the acyltransferase genes of the closely related plant species. The results showed that ElBAHD10 had the closest relationship with earlier reported ScCFAT and PhCFAT, which were found to catalyze the reaction of coniferyl alcohol to generate coniferyl acetate. The ElBAHD10gene was successfully cloned from E. lathyrisand subsequently expressed in Escherichia coli. The purified protein ElBAHD10 catalyzed the reaction of sinapyl alcohol with acetyl CoA and cinnamoyl CoA to form sinapyl acetate and sinapyl cinnamate, respectively. In contrast, the crude ElBAHD10 protein could catalyze sinapyl alcohol to directly generate methoxyeugenol. The recombinant E. colistrain expressing ElBAHD10 produced methoxyeugenol through whole-cell transformation. This study provides insights and lays the foundation for methoxyeugenol production through biosynthetic approaches.

Organic mixed ionic–electronic conductors, such as poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), are essential materials for the fabrication of bioelectronic devices due to their unique ability to couple and transport ionic and electronic charges. The growing interest in bioelectronic devices has led to the development of organic electrochemical transistors (OECTs) that can operate in aqueous solutions and transduce ionic signals of biological origin into measurable electronic signals. A common challenge with OECTs is maintaining the stability and performance of the PEDOT:PSS films operating under aqueous conditions. Although the conventional approach of blending the PEDOT:PSS dispersions with a cross-linker such as (3-glycidyloxypropyl)trimethoxysilane (GOPS) helps to ensure strong adhesion of the films to device substrates, it also impacts the morphology and thus electrical properties of the PEDOT:PSS films, which leads to a significant reduction in the performance of OECTs. In this study, we instead functionalize only the surface of the device substrates with GOPS to introduce a silane monolayer before spin-coating the PEDOT:PSS dispersion on the substrate. In all cases, having a GOPS monolayer instead of a blend leads to increased electronic performance metrics, such as three times higher electronic conductivity, volumetric capacitance, and mobility–capacitance product [μC*] value in OECT devices, ultimately leading to a record value of 406 ± 39 F cm–1V–1s–1for amorphous PEDOT:PSS. This increased performance does not come at the expense of operational stability, as both the blend and surface functionalization show similar performance when subjected to pulsed gate bias stress, long-term electrochemical cycling tests, and aging over 150 days. Overall, this study establishes a novel approach to using GOPS as a surface monolayer instead of a blended cross-linker, for achieving high-performance organic mixed ionic–electronic conductors that are stable in water for bioelectronics.

In early 2020, two unique events perturbed ship emissions of pollutants around Southern China, proffering insights into the impacts of ship emissions on regional air quality: the decline of ship activities due to COVID-19 and the global enforcement of low-sulfur (<0.5%) fuel oil for ships. In January and February 2020, estimated ship emissions of NOx, SO2, and primary PM2.5over Southern China dropped by 19, 71, and 58%, respectively, relative to the same period in 2019. The decline of ship NOxemissions was mostly over the coastal waters and inland waterways of Southern China due to reduced ship activities. The decline of ship SO2and primary PM2.5emissions was most pronounced outside the Chinese Domestic Emission Control Area due to the switch to low-sulfur fuel oil there. Ship emission reductions in early 2020 drove 16 to 18% decreases in surface NO2levels but 3.8 to 4.9% increases in surface ozone over Southern China. We estimated that ship emissions contributed 40% of surface NO2concentrations over Guangdong in winter. Our results indicated that future abatements of ship emissions should be implemented synergistically with reductions of land-borne anthropogenic emissions of nonmethane volatile organic compounds to effectively alleviate regional ozone pollution.

ABSTRACTIndoor positioning systems based on WiFi round-trip time (RTT) measurement were reported to deliver sub-metre-level accuracy using trilateration, under ideal indoor conditions. However, the performance of WiFi RTT positioning in complex, non-line-of-sight environment remains an open research question. To this end, this article investigates the properties of WiFi RTT in several real-world indoor environments on heterogeneous smartphones. We present three datasets collected on a large-scale building floor, an office room and an apartment. The datasets contain both RTT and received signal strength (RSS) signal measures with correct ground-truth labels for further research. Our results indicated that in a complex indoor environment, RTT fingerprinting system delivered an accuracy of 0.6 m which was 107% better than traditional RSS fingerprinting and 6 m better than RTT trilateration which failed to deliver sub-metre accuracy as claimed.

We study large-scale network embedding with the goal of generating high-quality embeddings for networks with more than 1 billion vertices and 100 billion edges. Recent attempts LightNE and NetSMF propose to sparsify and factorize the (dense) NetMF matrix for embedding large networks, where NetMF is a theoretically-grounded network embedding method. However, there is a trade-off between their embeddings’ quality and scalability due to their expensive memory requirements, making embeddings less effective under real-world memory constraints. Therefore, we present the SketchNE model, a scalable, effective, and memory-efficient network embedding solution developed for a single machine with CPU only. The main idea of SketchNE is to avoid the explicit construction and factorization of the NetMF matrix either sparsely or densely when producing the embeddings through the proposed sparse-sign randomized single-pass SVD algorithm. We conduct extensive experiments on nine datasets of various sizes for vertex classification and link prediction, demonstrating the consistent outperformance of SketchNE over state-of-the-art baselines in terms of both effectiveness and efficiency. SketchNE costs only 1.0 hours to embed the Hyperlink2012 network with 3.5 billion vertices and 225 billion edges on a CPU-only single machine with embedding superiority (e.g., a 282% relative HITS@10 gain over LightNE).

Alternate partial root-zone drip fertigation (ADF) is a combination of alternating irrigation and drip fertigation, with the potential to save water and increase nitrogen (N) fertilizer efficiency. A 2-year greenhouse experiment was conducted to evaluate the effect of different fertigation frequencies on the distribution of soil moisture and nutrients and tomato yield under ADF. The treatments included three ADF frequencies with intervals of 3 days (F3), 6 days (F6) and 12 days (F12), and conventional drip fertigation as a control (CK), which was fertilized once every 6 days. For the ADF treatments, two drip tapes were placed 10 cm away on each side of the tomato row, and alternate drip irrigation was realized using a manual valve on the distribution tapes. For the CK treatment, a drip tape was located close to the roots of the tomato plants. The total N application rate of all treatments was 180 kg ha−1. The total irrigation amounts applied to the CK treatment were 450.6 and 446.1 mm in 2019 and 2020, respectively; and the irrigation amounts applied to the ADF treatments were 60% of those of the CK treatment. The F3 treatment resulted in water and N being distributed mainly in the 0–40-cm soil layer with less water and N being distributed in the 40–60-cm soil layer. The F6 treatment led to 21.0 and 29.0% higher 2-year average concentration of mineral N in the 0–20 and 20–40-cm soil layer, respectively and a 23.0% lower N concentration in the 40–60-cm soil layer than in the CK treatment. The 2-year average tomato yields of the F3, F6, F12, and CK treatments were 107.5, 102.6, 87.2, and 98.7 t ha−1, respectively. The tomato yield of F3 was significantly higher (23.3%) than that in the F12 treatment, whereas there was no significant difference between the F3 and F6 treatment. The F6 treatment resulted in yield similar to the CK treatment, indicating that ADF could maintain tomato yield with a 40% saving in water use. Based on the distribution of water and N, and tomato yield, a fertigation frequency of 6 days under ADF should be considered as a water-saving strategy for greenhouse tomato production.

Objective: To investigate whether human short interspersed nuclear element antisense RNA (Alu antisense RNA; Alu asRNA) could delay human fibroblast senescence and explore the underlying mechanisms. Methods: We transfected Alu asRNA into senescent human fibroblasts and used cell counting kit-8 (CCK-8), reactive oxygen species (ROS), and senescence-associated beta-galactosidase (SA-β-gal) staining methods to analyze the anti-aging effects of Alu asRNA on the fibroblasts. We also used an RNA-sequencing (RNA-seq) method to investigate the Alu asRNA-specific mechanisms of anti-aging. We examined the effects of KIF15 on the anti-aging role induced by Alu asRNA. We also investigated the mechanisms underlying a KIF15-induced proliferation of senescent human fibroblasts. Results: The CCK-8, ROS and SA-β-gal results showed that Alu asRNA could delay fibroblast aging. RNA-seq showed 183 differentially expressed genes (DEGs) in Alu asRNA transfected fibroblasts compared with fibroblasts transfected with the calcium phosphate transfection (CPT) reagent. The KEGG analysis showed that the cell cycle pathway was significantly enriched in the DEGs in fibroblasts transfected with Alu asRNA compared with fibroblasts transfected with the CPT reagent. Notably, Alu asRNA promoted the KIF15 expression and activated the MEK-ERK signaling pathway. Conclusion: Our results suggest that Alu asRNA could promote senescent fibroblast proliferation via activation of the KIF15-mediated MEK-ERK signaling pathway.

The through silicon via (TSV) is one of the important enabling technologies of stacked 3-D ICs. However, the crosstalk is generated when signals are transmitted through the closely clustered TSVs due to the coupling effect. The crosstalk avoidance code (CAC) techniques have attracted great concerns in recent years, for the TSV-to-TSV crosstalk deteriorates the signal integrity. Nevertheless, the CAC techniques usually require specific shape of the TSV array, e.g., $3\times N$ array. This work proposes a crosstalk suppression scheme combining the CAC method and the static shielding technique, named Mosaic-3C1S. The proposed scheme is able to be applied to arbitrary rectangular TSV arrays. In the proposed scheme, the $2\times 2$ TSV subarray, which contains three signal TSVs and one shielding TSV, is used as the basic unit to tile the rectangular TSV array. The CAC method is applied to the signal TSVs in the $2\times 2$ subarrays, and the raw data are transmitted by the rest boundary TSVs, if any. In order to further reduce the bit overhead, a triangular numeral system (TNS)-based CAC, named TNS-CAC, is proposed and applied. The simulation results show that the proposed TNS-CAC has advantages on bit overhead and codec area. The proposed Mosaic-3C1S scheme with TNS-CAC is able to suppress the crosstalk between TSVs to 6C level. The bit overhead of the proposed scheme is between 25% and 45%, which is lower than that of the previous CAC methods for TSV arrays for the most cases.

As an essential part of the global water cycle, the effective detection of snow depth is of great significance to the study of climate change. Global navigation satellite system interferometric reflectometry (GNSS-IR) technology emerged as a new ground-based snow depth monitoring method. The principle is to invert the height of the reflection surface according to the signal-to-noise ratio (SNR) at a low elevation angle. However, the topographic relief in the reflection area of GNSS stations often dramatically impacts the accuracy of snow depth inversion. This study proposes a terrain tilt correction (TTC) algorithm based on different azimuth intervals to address it. Taking the P351 and P676 stations in the United States as examples, the snow depth inversion research of different systems is carried out. In the P351 station with gentle terrain, the TTC algorithm can maintain the stable accuracy. In the P676 station with steep terrain, the TTC algorithm can effectively compensate for the error caused by the landscape and significantly improve the accuracy of snow depth inversion. The experimental results of the two stations show that the snow depth inversion results of different systems after TTC are consistent with the in situ snow depth provided by the respective meteorological stations. Subsequently, a Helmert variance component estimation (HVCE) weighting algorithm is introduced for multisystem combinations based on different systems with different snow depth inversion accuracies, and the feasibility and stability of the combination strategy are investigated. Compared with the in situ snow depth, the correlation coefficient ( $R$ ) of the combined snow depth at the P351 station is 0.91, the root-mean-square error (RMSE) is 19.7 cm, and the mean error (ME) is −12.2 cm. The snow depth obtained by the combination of the multisystem at the P676 station has an $R$ of 0.95, an RMSE of 9.9 cm, and an ME of −4.9 cm. Compared with HVCE weighting before TTC, the RMSE is reduced by 53.3%, and the absolute value of ME is reduced by 74.2%. This study is not only of great significance for high-precision snow depth monitoring but also provides a necessary technical reference for further research on multisystem combined.

Byline: Wen-Zhou. Liu, Yu. Sun, Xu. Feng, Xiao-Han. Bi, Tao. Liu, Hua-Fu. ZhouAim of Study: The conclusions on the association between glutathione S-transferase P1 (GSTP1) gene polymorphism and lung cancer [...]

• Ba 5 Si 8 O 21 composite with high crystallinity was achieved by a glass crystallization strategy. • The scintillating composite with large size and complicated shape can be achieved. • The improved mechanical properties with nearly double hardness can be realized. • The outstanding scintillation property with the light yield of about 15,000 pH/MeV can be achieved in Eu-doped composite. The construction of scintillating ceramics is of great technological importance for various fundamental applications, including medical diagnostic, security inspection, resource exploration and particle physics. The chief challenge is the facile and scalable synthesis of scintillating ceramics with the desirable combination of pore-free, reliable mechanical properties and excellent scintillating performance. Here we present a pressureless glass crystallization strategy for the construction of scintillating composite with high crystallinity. The fabricated scintillating composites are featured by small optical turbidity, excellent mechanical properties, and efficient scintillating luminescence with the scintillating light yield of 15,000 pH/MeV and about 2.46 times higher than that of the commercial BGO single crystal. Moreover, the scintillating composite derived radiation detector device is successfully elaborated. The practical application for monitoring gamma ray is demonstrated and the precision of the device is less than that of the tolerable deviation of 30%. Our results suggest an innovative approach for expanding the category of scintillating material candidates, pointing to practical application in the field of radiation detection. [Display omitted] [ABSTRACT FROM AUTHOR]

Lipid‐lowering drugs, especially statins, are extensively utilized in clinical settings for the prevention of hyperlipidemia. Nevertheless, prolonged usage of current lipid‐lowering medications is associated with significant adverse reactions. Therefore, it is imperative to develop novel therapeutic agents for lipid‐lowering therapy. In this study, a chenodeoxycholic acid and lactobionic acid double‐modified polyethyleneimine (PDL) nanocomposite as a gene delivery vehicle for lipid‐lowering therapy by targeting the liver, are synthesized. Results from the in vitro experiments demonstrate that PDL exhibits superior transfection efficiency compared to polyethyleneimine in alpha mouse liver 12 (AML12) cells and effectively carries plasmids. Moreover, PDL can be internalized by AML12 cells and rapidly escape lysosomal entrapment. Intravenous administration of cyanine5.5 (Cy5.5)‐conjugated PDL nanocomposites reveals their preferential accumulation in the liver compared to polyethyleneimine counterparts. Systemic delivery of low‐density lipoprotein receptor plasmid‐loaded PDL nanocomposites into mice leads to reduced levels of low‐density lipoprotein cholesterol (LDL‐C) and triglycerides (TC) in the bloodstream without any observed adverse effects on mouse health or well‐being. Collectively, these findings suggest that low‐density lipoprotein receptor plasmid‐loaded PDL nanocomposites hold promise as potential therapeutics for lipid‐lowering therapy. This work focuses on the schematic illustration of PDL preparation and intracellular delivery of PDL/pLDLR for gene therapy.

This article presents svds-C, an open-source and high-performance C program for accurately and robustly computing truncated SVD, e.g. computing several largest singular values and corresponding singular vectors. We have re-implemented the algorithm of svdsin Matlab in C based on MKL or OpenBLAS and multi-thread computing to obtain the parallel program named svds-C. svds-Crunning on shared-memory computer consumes less time and memory than svdsthanks to careful implementation of multi-thread parallelization and memory management. Numerical experiments on different test cases which are synthetically generated or directly from real-world datasets show that, svds-Cruns remarkably faster than svdswith averagely 4.7X and at most 12X speedup for 16-thread parallel computing on a computer with Intel CPU, while preserving same accuracy and consuming about half memory space. Experimental results also demonstrate that svds-Chas similar advantages over svdson the computer with AMD CPU, and outperforms other state-of-the-art algorithms for truncated SVD on computing time and robustness.

Byline: Xu. Feng, Xiaoyong. Xie, Baoshi. Zheng, Chaoyang. Peng, Huafu. Zhou, Jiajin. Qin Background: Nonsmall cell lung cancer (NSCLC) is one of the leading incidence and mortality of malignant tumors [...]

We report the first experimental characterization of isomerically pure and pristine C120fullertubes, [5,5] C120-D5d(1) and [10,0] C120-D5h(10766). These new molecules represent the highest aspect ratio fullertubes isolated to date; for example, the prior largest empty cage fullertube was [5,5] C100-D5d(1). This increase of 20 carbon atoms represents a gigantic leap in comparison to three decadesof C60–C90fullerene research. Moreover, the [10,0] C120-D5d(10766) fullertube has an end-cap derived from C80-Ihand is a new fullertube whose C40end-cap has not yet been isolated experimentally. Theoretical and experimental analyses of anisotropic polarizability and UV–vis assign C120isomer I as a [5,5] C120-D5d(1) fullertube. C120isomer II matches a [10,0] C120-D5h(10766) fullertube. These structural assignments are further supported by Raman data showing metallic character for [5,5] C120-D5d(1) and nonmetallic character for C120-D5h(10766). STM imaging reveals a tubular structure with an aspect ratio consistent with a [5,5] C120-D5d(1) fullertube. With microgram quantities not amenable to crystallography, we demonstrate that DFT anisotropic polarizability, augmented by long-accepted experimental analyses (HPLC retention time, UV–vis, Raman, and STM) can be synergistically used (with DFT) to down select, predict, and assign C120fullertube candidate structures. From 10 774 mathematically possible IPR C120structures, this anisotropic polarizability paradigm is quite favorable to distinguish tubular structures from carbon soot. Identification of isomers I and II was surprisingly facile, i.e., two purified isomers for two possible structures of widely distinguishing features. These metallic and nonmetallic C120fullertube isomers open the door to both fundamental research and application development.

ABSTRACTThis study focuses on an anomaly in the intramonth pattern of stock returns and defines it as the ‘month-end effect’. The mean return for stocks is negative for the month-end days. Moreover, this study provides an economically plausible explanation for the month-end effect, namely, the liquidity hypothesis. It is suggested that the increase in the liquidity demand of commercial banks at the month-end days generally induces a fall in stock returns at the end of each month. Finally, additional evidence is provided that the window dressing hypothesis and macroeconomic news announcements hypothesis have limited explanation for the month-end effect.

A successful Cu-catalyzed addition of both Cl and SO2OCF2H groups into alkenes allows us to discover the unusual reactivity of the SO2OCF2H group. As opposed to common sulfonic esters (RSO2-O-R′), in which the R′ group is highly electrophilic, the SO2moiety demonstrates higher electrophilicity in RSO2–OCF2H. The unexpected reactivity is further developed not only as a synthetic tool for well-functionalized alkenyl sulfonyl fluorides but also for the first 18F labeling of alkenyl sulfonyl fluorides.

Anomaly detection is one of the most active research areas in various critical domains, such as healthcare, fintech, and public security. However, little attention has been paid to scholarly data, that is, anomaly detection in a citation network. Citation is considered as one of the most crucial metrics to evaluate the impact of scientific research, which may be gamed in multiple ways. Therefore, anomaly detection in citation networks is of significant importance to identify manipulation and inflation of citations. To address this open issue, we propose a novel deep graph learning model, namely graph learning for anomaly detection (GLAD), to identify anomalies in citation networks. GLAD incorporates text semantic mining to network representation learning by adding both node attributes and link attributes via graph neural networks (GNNs). It exploits not only the relevance of citation contents, but also hidden relationships between papers. Within the GLAD framework, we propose an algorithm called Citation PUrpose (CPU) to discover the purpose of citation based on citation context. The performance of GLAD is validated through a simulated anomalous citation dataset. Experimental results demonstrate the effectiveness of GLAD on the anomalous citation detection task. [ABSTRACT FROM AUTHOR]

One of the most popular approaches for indoor positioning is WiFi fingerprinting, which has been intrinsically tackled as a traditional machine learning problem since the beginning, to achieve a few metres of accuracy on average. In recent years, deep learning has emerged as an alternative approach, with a large number of publications reporting sub-metre positioning accuracy. Therefore, this survey presents a timely, comprehensive review of the most interesting deep learning methods being used for WiFi fingerprinting. In doing so, we aim to identify the most efficient neural networks, under a variety of positioning evaluation metrics for different readers. We will demonstrate that despite the new emerging WiFi signal measures (i.e. CSI and RTT), RSS produces competitive performances under deep learning. We will also show that simple neural networks outperform more complex ones in certain environments.

Graphical Abstract:

Bi-activated photonic materials are promising for various applications in high-capacity telecommunication, tunable laser, and advanced bioimaging and sensing. Although various Bi-doped material candidates have been explored, manufacturing of Bi heavily doped fiber with excellent optical activity remains a long-standing challenge. Herein, a novel viscosity evolutional behavior mediated strategy for manufacturing of Bi-doped active fiber with high dopant solubility is proposed. The intrinsic relation among the evolution of Bi, reaction temperature and viscosity of the glass system is established. Importantly, the effective avenue to prevent the undesired deactivation of Bi during fiber drawing by tuning the temperature dependent viscosity evolution is built. By applying the strategy, for the first time we demonstrate the success in fabrication of heavily doped Bi active fiber. Furthermore, the principal fiber amplifier device is constructed and broadband optical signal amplification is realized. Our findings indicate the effectiveness of the proposed temperature dependent viscosity mediated strategy for developing novel photonic active fiber, and they also demonstrate the great potential for application in the next-generation high-capacity telecommunication system.

Phenylphenalenones (PhPNs), phytoalexins in wild bananas (Musaceae), are known to act against various pathogens. However, the abundance of PhPNs in many Musaceae plants of economic importance is low. Knowledge of the biosynthesis of PhPNs and the application of biosynthetic approaches to improve their yield is vital for fighting banana diseases. However, the processes of PhPN biosynthesis, especially those involved in methylation modification, remain unclear. Musella lasiocarpais a herbaceous plant belonging to Musaceae, and due to the abundant PhPNs, their biosynthesis in M. lasiocarpahas been the subject of much attention. In this study, we assembled a telomere-to-telomere gapless genome of M. lasiocarpaas the reference, and further integrated transcriptomic and metabolomic data to mine the candidate genes involved in PhPN biosynthesis. To elucidate the diversity of PhPNs in M. lasiocarpa, three screened O-methyltransferases (Ml01G0494, Ml04G2958, and Ml08G0855) by phylogenetic and expressional clues were subjected to in vitroenzymatic assays. The results show that the three were all novel O-methyltransferases involved in the biosynthesis of PhPN phytoalexins, among which Ml08G0855 was proved to function as a multifunctional enzyme targeting multiple hydroxyl groups in PhPN structure. Moreover, we tested the antifungal activity of PhPNs against Fusarium oxysporumand found that the methylated modification of PhPNs enhanced their antifungal activity. These findings provide valuable genetic resources in banana breeding and lay a foundation for improving disease resistance through molecular breeding.

Sperm motility can be enhanced by adding ATP exogenously during in vitrofertilization. However, administering exogenous ATP to the testis to improve sperm motility for in vivoasthenozoospermia treatment has not been investigated yet. Inspired by the recent advances in nanomedicine, we investigated whether the capability of drug delivery nanocarriers to traverse the blood–testis barrier (BTB) can facilitate ATP-dependent asthenozoospermia treatment. We found that the human H-ferritin (HFn) nanocarrier possesses the capability to traverse the BTB and specifically targets the head of elongated sperm cells. Specifically, the HFn nanocarrier traversed the BTB and accumulated in the sperm heads by binding with the HFn receptor (HFR), whose expression was relatively low in Sertoli cells but high in sperm heads. In a gossypol-induced mouse asthenozoospermia model, the administration of an ATP-loaded HFn nanocage through a tail vein injection significantly improved sperm motility. Moreover, the HFn nanocarrier was not toxic to mice in the short (1d) and long terms (30d, 90d) nor did it affect their reproductive health. Thus, the ATP-loaded HFn nanocarrier can potentially serve as a drug-delivery system for treating asthenozoospermia.

The Barrow Sub-basin and Exmouth Plateau, of Australia’s North West Shelf, contain Australia’s largest gas reserves, underpinning the three major LNG facilities, including Gorgon, Wheatstone and Pluto. In addition, there remains significant near-field exploration potential such as the Sasanof prospect. While there is full 3D seismic coverage in the basin, the existing 3D surveys are of different vintages covering only parts of the basin with diverse acquisition and processing parameters. Multi-Client Resources has produced an extensive 3D seismic reprocessing project (BEX-MC3D) incorporating 23 legacy 3D surveys to provide a seamless 25 570 km2 3D dataset. The BEX-MC3D was processed from field tape through DUG Technology’s advanced Broadband PreSDM processing sequence with Full Waveform Inversion (FWI) imaging. The BEX-MC3D provides one continuous superlative 3D dataset covering almost the entire Barrow Sub-basin and the Exmouth Plateau. Major geological surfaces corresponding to key tectonic events from overburden to reservoirs have been interpreted from the BEX-MC3D Priority area in the current study. These high-fidelity imaged surfaces form a basin-wide framework for: (1) rapid exploration lead and prospect identification through the creation of trap and reservoir visualisations; (2) improved reservoir connectivity analysis and modelling of producing and discovered fields to support better reservoir management and field development decisions; and (3) improved understanding of basin-burial history for reservoir quality and geo-mechanical property prediction. This paper will present and discuss major geological surfaces in the context of future exploration lead/prospect identification, reservoir characterisation for field development and management, and improving overall understanding of the basin history.

A numerical study of supercritical CO2two-phase flow in the ejector was carried out by computational fluid dynamics (CFD) methods. Through the comparison of simulation results and available experimental data in the literature, the accuracy of the three-dimensional CFD model was verified. A comparison of the effects of four turbulence models on the simulation calculation results was also presented. The distributions of pressure, velocity, two-phase volume fraction, shock wave and exergy flux inside the ejector were analyzed. The effects of the mixing section geometry on the performance of the ejector were obtained. Then, the entrained performance of the ejector was investigated by changing the area ratio between the constant-area mixing chamber and the outlet of the motive nozzle (AR) and the ratio between the length and the diameter of the constant-area mixing chamber (LDR). Finally, the optimum AR and LDR were determined to be 8.3 and 8.1, respectively based on the maximum entrained ratio and the minimum exergy destruction. Through optimizing the mixing chamber geometry, the minimum total exergy destruction and the maximum mass entrainment ratio (MER) of the ejector can attain 0.33 J/(kg·K) and 0.698 respectively.

In this study, Nie et al. performed proteome profiling with label-free quantification in control and single/double-KO cells of USP7 and its closest homolog, USP47, and for the first time revealed the proteome changes caused by USP7 and/or USP47 depletion. Their proteome-wide analysis uncovered potential USP7 substrates, which provides a resource for further functional studies.

Background: The presence of clinically significant portal hypertension (CSPH) remains a relative contraindication to liver resection for patients with resectable hepatocellular carcinoma (HCC). The goal of this study was to explore whether a laparoscopic approach could extend the indications for hepatectomy to patients with PH. Method: Patients who underwent laparoscopic liver resection (LLR) from February 2016 to September 2019 performed by a single medical team were included in this study. We analyzed the surgical and oncological outcomes between groups with and without CSPH before and after propensity score matching (PSM). Result: We enrolled 156 patients divided into two groups according to the presence (CSPH, n= 26) or absence (non-CSPH, n= 130) of CSPH. CSPH group was associated with more clinical signs of liver dysfunction (p&lt; 0.05). After PSM (n= 48 patients), the CSPH group tended to have a longer postoperative hospital stay (p= 0.054); however, there was no difference in operation time (p= 0.329), blood loss volume (p= 0.392), transfusion rates (p= 0.701), rate of conversion to open surgery (p= 0.666), surgical margin (p = 0.306), surgical mortality (n= 0), or comprehensive complication index (p= 0.844) between the two groups. The median follow-up time for the entire cohort was 19.6 months (range 0.2–40.6 months). The 3-year overall survival rate was 62.9% in the CSPH group and 84.3% in the non-CSPH group (p= 0.1090), and results were similar after PSM (p= 0.5734). Conclusions: LLR is safe and feasible for HCC with PH. The introduction of minimally invasive surgery, represented by LLR, can appropriately expand the indications for hepatectomy.

Effective mitigation of surface ozone pollution entails detailed knowledge of the contributing precursors’ sources. We use the GEOS-Chem adjoint model to analyze the precursors contributing to surface ozone in the Beijing–Tianjin–Hebei area (BTH) of China on days of different ozone pollution severities in June 2019. We find that BTH ozone on heavily polluted days is sensitive to local emissions, as well as to precursors emitted from the provinces south of BTH (Shandong, Henan, and Jiangsu, collectively the SHJ area). Heavy ozone pollution in BTH can be mitigated effectively by reducing NOx(from industrial processes and transportation), ≥C3alkenes (from on-road gasoline vehicles and industrial processes), and xylenes (from paint use) emitted from both BTH and SHJ, as well as by reducing CO (from industrial processes, transportation, and power generation) and ≥C4alkanes (from industrial processes, paint and solvent use, and on-road gasoline vehicles) emissions from SHJ. In addition, reduction of NOx, xylene, and ≥C3alkene emissions within BTH would effectively decrease the number of BTH ozone-exceedance days. Our analysis pinpoint the key areas and activities for locally and regionally coordinated emission control efforts to improve surface ozone air quality in BTH.

Patients with cirrhosis face a heightened risk of complications, underscoring the importance of identification. We have developed a Connectome strategy that combines metabolites with peptide spectral matching (PSM) in proteomics to integrate metabolomics and proteomics, identifying specific metabolites bound to blood proteins in cirrhosis using open search proteomics methods. Analysis methods including Partial Least Squares Discriminant Analysis (PLS-DA), Uniform Manifold Approximation and Projection (UMAP), and hierarchical clustering were used to distinguish significant differences among the Cirrhosis group, Chronic Hepatitis B (CHB) group, and Healthy group. In this study, we identified 81 cirrhosis-associated connectomes and established an effective model distinctly distinguishing cirrhosis from chronic hepatitis B and healthy samples, confirmed by PLS-DA, hierarchical clustering analysis, and UMAP analysis, and further validated using six new cirrhosis samples. We established a Unified Indicator for Identifying cirrhosis, including tyrosine, Unnamed_189.2, thiazolidine, etc., which not only enables accurate identification of cirrhosis groups but was also further validated using six new cirrhosis samples and extensively supported by other cirrhosis research data (PXD035024). Our study reveals that characteristic cirrhosis connectomes can reliably distinguish cirrhosis from CHB and healthy groups. The established unified cirrhotic indicator facilitates the identification of cirrhosis cases in both this study and additional research data.

The exploration of transition metal-based electrode materials for asymmetric supercapacitors has garnered considerable interest owing to their potential to achieve high-energy storage and demonstrate outstanding electrochemical performance. In this study, we designed and synthesized Zn-doped NiCo layered double hydroxide (LDH), a hollow supercapacitor electrode material, through a facile ion exchange method at room temperature. Doping Zn ions results in an increased interlayer spacing expanding from 0.815 nm (ZIF-67@NiCo-LDH) to 0.874 nm (ZnNiCo-LDH-7), which facilitates sufficient penetration of the electrolyte and accelerates the charge transfer kinetics. Moreover, by employing the metal-organic framework ZIF-67 as a precursor, ZnNiCo-LDH nanosheets assembled in hollow nanocages exhibit remarkable electrochemical performance due to their large contact area with electrolytes and superior electrical conductivity. The synthesized ZnNiCo-LDH electrode material achieves a high specific capacitance of 1908 F g−1at 1 A g−1. When integrated into an asymmetric supercapacitor, in combination with activated carbon (AC), the device delivers an outstanding energy density of 41 Wh kg−1at a power density of 825 W kg−1. Notably, the assembled device shows exceptional cycling stability, retaining 120 % of its initial specific capacitance even after 5000 cycles at a current density of 5 A g−1. The extraordinary performance and remarkable stability are mainly due to Zn ion doping-induced local lattice expansion and the hierarchical hollow nanocage structure, which underscores its highly promising potential in supercapacitor applications.

Inhibition of oxidative stress and ferroptosis is currently considered to be a promising therapeutic approach for neurodegenerative diseases. Herpotrichones, a class of compounds derived from insect symbionts, have shown potential for neuroprotective activity with low toxicity. However, the specific mechanisms through which herpotrichones exert their neuroprotective effects remain to be fully elucidated. In this study, the natural [4 + 2] adducts herpotrichone A (He-A) and its new analogues were isolated from the isopod-associated fungus Herpotrichiasp. SF09 and exhibited significantly protective effects in H2O2-, 6-OHDA-, and RSL3-stimulated PC12 cells and LPS-stimulated BV-2 cells. Moreover, He-Awas able to relieve ferroptotic cell death in RSL3-stimulated PC12 cells and 6-OHDA-induced zebrafish larvae. Interestingly, He-Acan activate antioxidant elements and modulate the SLC7A11 pathway without capturing oxidic free radical and chelating iron. These findings highlight He-Aas a novel hit that protects against ferroptosis-like neuronal damage in the treatment of neurodegenerative diseases.

The evaporative emissions of anthropogenic volatile organic compounds (AVOCs) are sensitive to ambient temperature. This sensitivity forms an air pollution-meteorology connection that has not been assessed on a regional scale. We parametrized the temperature dependence of evaporative AVOC fluxes in a regional air quality model and evaluated the impacts on surface ozone in the Beijing–Tianjin–Hebei (BTH) area of China during the summer of 2017. The temperature dependency of AVOC emissions drove an enhanced simulated ozone-temperature sensitivity of 1.0 to 1.8 μg m–3K–1, comparable to the simulated ozone-temperature sensitivity driven by the temperature dependency of biogenic VOC emissions (1.7 to 2.4 μg m–3K–1). Ozone enhancements driven by temperature-induced AVOC increases were localized to their point of emission and were relatively more important in urban areas than in rural regions. The inclusion of the temperature-dependent AVOC emissions in our model improved the simulated ozone-temperature sensitivities on days of ozone exceedance. Our results demonstrated the importance of temperature-dependent AVOC emissions on surface ozone pollution and its heretofore unrepresented role in air pollution–meteorology interactions.

Although fullerenes were discovered nearly 35 years ago, scientists still struggle to isolate “single molecule” tubular fullerenes larger than C90. In similar fashion, there is a paucity of reports for pristine single-walled carbon nanotubes (SWNTs). In spite of Herculean efforts, the isolation and properties of pristine members of these carbonaceous classes remain largely unfulfilled. For example, the low abundance of spherical and tubular higher fullerenes in electric-arc extracts (<0.01–0.5%) and multiplicity of structural isomers remain a major challenge. Recently, a new isolation protocol for highly tubular fullerenes, also called f ullertubes, was reported. Herein, we describe spectroscopic characterization including 13C NMR, XPS, and Raman results for purified [5,5] fullertube family members, D5h-C90and D5d-C100. In addition, DFT computational HOMO–LUMO gaps, polarizability indices, and electron density maps were also obtained. The Raman and 13C NMR results are consistent with semiconducting and metallic properties for D5h-C90and D5d-C100, respectively. Our report suggests that short [5,5] fullertubes with aspect ratios of only ∼1.5–2 are metallic and could exhibit unique electronic properties.

Protein–protein interactions (PPIs) play vital roles in regulating biological processes, such as cellular and signaling pathways. Hotspots are certain residues located at protein–protein interfaces that contribute more in protein–protein binding than other residues. Research on the mutational effects of hotspots is important for understanding basic aspects of protein association. Hence, various computational tools have been developed to explore the impact of mutation hotspots, which will allow a better understanding of the forces that drive PPIs. However, tools that may provide comprehensive substitutions at hotspots are still rare. Hence, there is a strong need for a new free web server to explore mutational effects of hotspots. Herein we introduce a web server named PIIMS that integrates molecular dynamics simulation and one-step free energy perturbation. It contains two main computational functions: (1) computational alanine scanning analysis to identify hotspots and (2) full mutation scanning analysis to evaluate the effects of hotspot mutations. We rigidly validated its ability to predict binding free energy changes by using large and diverse datasets including 1,341 mutations from 50 PPIs with the correlation coefficient R= 0.75. The difference from the existing tools is that PIIMS can perform further evaluation of hotspot residues with regard to their different mutations. The PIIMS web server (accessible at http://chemyang.ccnu.edu.cn/ccb/server/PIIMS/index.php) is free and open to all users without login requirements.

The immense reduction in aerosol levels during the COVID-19 pandemic provides an opportunity to reveal how atmospheric chemistry is regulating our climate, among which the effect of aerosols on climate is a phenomenon of great interest but still in hot debate. The Intergovernmental Panel on Climate Change (IPCC) has continually identified the effect of aerosols on climate to have the largest uncertainty among the factors contributing to global climate change. Several studies indicate an inverse relationship between aerosol presence in the atmosphere and the diurnal surface air temperature range (DTR). Herein, we test this relationship by analyzing the DTR values from in situweather station records for periods before and during the COVID-19 epidemic in China where aerosol levels have substantially reduced, compared with the climatological mean levels for a 19 year period. Our analyses find that DTRs from February to June during the COVID-19 pandemic are greater than 3 standard deviations above the climatological mean DTR. This anomaly has never occurred before in the 21stcentury and is at least in part associated with the observed reduction in aerosols.

To systematically identify the substrates of RNF146 that are targeted for degradation, quantitative proteome and transcriptome analyses were performed in RNF146 KO and TNKS1/2 DKO cells. We identified 160 potential substrates of RNF146, which include many known substrates of RNF146 and TNKS1/2 as well as 122 potential TNKS-independent substrates of RNF146.

New fluorescent probes with up to 244 nm Stokes shift were synthesized to detect diethyl chlorophosphate (DCP), a mimic of lethal nerve agents. These BINOL-Si complexes showed rapid, sensitive and naked eye recognition through a specific reaction. Noteworthy, a fiber optic sensor capable of detecting DCP vapor in real time was also invented for the first time.

Bone destruction in inflammatory osteolytic diseases including periodontitis is related to excessive activity of osteoclasts (OC), which originate from precursor cells of the myeloid lineage, termed osteoclast precursors (OCP). In contrast to ample knowledge that we currently have on mature OC, little is known about OCP and their regulation during bacterial infection. Therefore, this study aimed to identify and characterize OCP following chronic infection with a periodontal bacteria Porphyromonas gingivalis(Pg). We used a microosmotic pump to continually release Pgsubcutaneously in a murine model. Two weeks after Pginfection, the frequency of CD11b+c‐fms+Ly6Chipopulation is significantly elevated within the bone marrow, spleen, and peripheral blood. In vitro and in vivo studies identified these cells as the OCP‐containing population and Pginfection significantly enhanced the osteoclastogenic activity of these cells. Furthermore, mRNA sequencing analysis indicated a unique gene and pathway profile in CD11b+c‐fms+Ly6Chipopulation following Pginfection, with changes in genes and pathways related to OC differentiation, cell proliferation and apoptosis, inflammatory response, phagocytosis, and immunity, as well as antigen processing and presentation. Moreover, using IL‐6 knockout mice, we found that IL‐6 is important for Pg‐induced accumulation of CD11b+c‐fms+Ly6Chipopulation from the bone marrow and periphery. Our results provide new insight into the characterization and regulation of OCP following a chronic bacterial infection. This knowledge is relevant to the understanding of the pathogenesis of bacteria‐induced bone loss, and to the identification of potential therapeutic targets of bone loss diseases. Chronic Porphyromonas gingivalisinfection promotes CD11b+c‐fms+Ly6ChiOCP accumulation in BM and periphery through elevated serum IL‐6 and enhances their osteoclastogenic potential through changed gene signatures

A modified TCAR method to improve the NL ambiguity resolution over medium-long baseline is presented. The estimated DD ionospheric delay derived from the Kalman-filter floating solution is adopted to modify the floating NL ambiguities. Modified by the smooth DD ionospheric delay, the NL ambiguity residuals are mostly within 0.5 cycles over medium-long baselines, showing a significant improvement in contrast to the classical TCAR method. The positioning performances of the modified method are even better than the LAMBDA method over 72 and 634 km baselines. As the ambiguity can be correctly fixed just after several epochs, high-precision positioning can be achieved in a very short time.

ABSTRACTWe discuss the existence and derivation of the asset growth anomaly in China’s A-share market. Our findings suggest that there is a negative relationship between the asset growth rate and future returns during 2008 to 2016 in the Chinese stock market. Furthermore, we investigate whether the asset growth anomaly is derived from mispricing or risk premia. Our tests reveal that it is the asset growth rate characteristic that predicts returns, which indicate investors misprice the asset growth rate characteristic and raise doubts regarding the risk explanation.

Inhibitors of checkpoint kinase 1 (CHK1), a central component of DNA damage and cell cycle checkpoint response, represent a promising new cancer therapy, but the global cellular functions they regulate through phosphorylation are poorly understood. To elucidate the CHK1-regulated phosphorylation network, we performed a global quantitative phosphoproteomics analysis, which revealed 142 phosphosites whose phosphorylation levels were significantly different following treatment with the CHK1 inhibitor SCH 900776. Bioinformatics analysis identified phosphoproteins that function in ATR–CHK1 signaling, DNA replication, and DNA repair. Furthermore, IRF3 phosphorylation at S173 and S175 was significantly reduced following treatment with SCH 900776. Our findings indicate that the CHK1-dependent regulation of IRF3 phosphorylation at S173 and S175 may play a role in the induction of innate immune response after replication stress or DNA damage, which suggests a potential function of CHK1 in the innate immune response. Data are available via ProteomeXchange with identifier PXD015125.

Aurora kinases are a family of serine/threonine kinases vital for cell division. Because of the overexpression of Aurora kinases in a broad range of cancers and their important roles in mitosis, inhibitors targeting Aurora kinases have attracted attention in cancer therapy. VX-680 is an effective pan-Aurora kinase inhibitor; however, its clinical efficacy was not satisfying. In this study, we performed CRISPR/Cas9 screens to identify genes whose depletion shows synthetic lethality with VX-680. The top hit from these screens was GSG2 (also known as Haspin), a serine/threonine kinase that phosphorylates histone H3 at Thr-3 during mitosis. Moreover, both Haspin knockout and Haspin inhibitor-treated HCT116 cells were hypersensitive to VX-680. Furthermore, we showed that the synthetic lethal interaction between Haspin depletion and VX-680 was mediated by the inhibition of Haspin with Aurora kinase B (AURKB), but not with Aurora kinase A (AURKA). Strikingly, combined inhibition of Haspin and AURKB had a better efficacy than single-agent treatment in both head and neck squamous cell carcinoma and non-small cell lung cancer. Taken together, our findings have uncovered a synthetic lethal interaction between AURKB and Haspin, which provides a strong rationale for this combination therapy for cancer patients.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been identified as one of the most significant targets in herbicide discovery for resistant weed control. In a continuing effort to discover potent novel HPPD inhibitors, we adopted a ring-expansion strategy to design a series of novel pyrazole–quinazoline-2,4-dione hybrids based on the previously discovered pyrazole–isoindoline-1,3-dione scaffold. One compound, 3-(2-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-1H-pyrazole-4-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione (9bj), displayed excellent potency against AtHPPD, with an IC50value of 84 nM, which is approximately 16-fold more potent than pyrasulfotole (IC50= 1359 nM) and 2.7-fold more potent than mesotrione (IC50= 226 nM). Furthermore, the co-crystal structure of the AtHPPD–9bjcomplex (PDB ID 6LGT) was determined at a resolution of 1.75 Å. Similar to the existing HPPD inhibitors, compound 9bjformed a bidentate chelating interaction with the metal ion and a π–π stacking interaction with Phe381 and Phe424. In contrast, o-chlorophenyl at the N3 position of quinazoline-2,4-dione with a double conformation was surrounded by hydrophobic residues (Met335, Leu368, Leu427, Phe424, Phe392, and Phe381). Remarkably, the greenhouse assay indicated that most compounds displayed excellent herbicidal activity (complete inhibition) against at least one of the tested weeds at the application rate of 150 g of active ingredient (ai)/ha. Most promisingly, compounds 9ajand 9binot only exhibited prominent weed control effects with a broad spectrum but also showed very good crop safety to cotton, peanuts, and corn at the dose of 150 g of ai/ha.

The reason for the reduced efficacy of lung cancer therapy is the existence of lung cancer stem cells (CSCs). Targeting CSCs results in evolved phenotypes with increased malignancy, leading to therapy failure. Here, we propose a new therapeutic strategy: investigating the “transitional” cells that represent the stage between normal lung stem cells and lung CSCs. Identifying and targeting the key molecule that drives carcinogenesis to inhibit or reverse this process would thus provide new perspectives for early diagnosis and intervention in lung cancer. We used Gprc5a-knockout (KO) mice, the first animal model of spontaneous lung adenocarcinoma established by the deletion of a single lung tumor suppressor gene. We investigated the interaction of lung progenitor cells AT2 with Lgr5 cells in the generation of CSCs and related signaling mechanism. In the present study, using Gprc5a-KO mice, we found the initiator Sca-1+Abcg1+subset with a CSC-like phenotype within the lung progenitor AT2 cell population in mice that had not yet developed tumors. We confirmed the self-renewal and tumor initiation capacities of this subset in vitro, in vivo, and clinical samples. Mechanistically, we found that the generation of Sca-1+Abcg1+cells was associated with an interaction between AT2 and Lgr5 cells and the subsequent activation of the ECM1-α6β4-ABCG1 axis. Importantly, Sca-1+Abcg1+and SPA+ABCG1+cells specifically existed in the small bronchioles of Gprc5a-KO mice and patients with pneumonia, respectively. Thus, the present study unveiled a new kind of lung cancer-initiating cells (LCICs) and provided potential markers for the early diagnosis of lung cancer.