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Innovation is an important approach to boost economic development and social advances, and innovative talents are the cornerstone of the development of the pharmaceutical industry. Conventional pharmaceutical education is not, however, tightly interconnected with current developments because pharmaceutical training lacks practicality and innovation. A deep integration of industry–university–research (IUR) would be a significant approach to solve this issue. In view of this, the School of Pharmacy of Jilin Medical University has thus integrated its own specialized characteristics with regional industrial strength to build a “one core, three chains, and four platforms” talent training mode, with “IUR collaborative education” as the core, “knowledge chain–capability chain–quality chain” as the inner spiral, and “teaching platform–research platform–enterprise platform–social platform” as the external spiral. Under the background of the deep integration of IUR, the quality of talent training is comprehensively improved by taking the “Double Hundred–double Entering” action as an opportunity (100 entrepreneurs enter the campus and 100 doctoral faculty members enter enterprises), relying on the Modern Pharmaceutical Industry College, using scientific research feedback teaching as the driving force and projects and competitions as the starting point. This cultivation pattern has achieved positive results in practice and effectively improved the training quality of innovative talents in our university. It can provide a reference for the talent cultivation of related majors in similar universities.

Four new p-terphenyl derivatives, talaroterphenyls A–D (1–4), together with three biosynthetically related known ones (5–7), were obtained from the mangrove sediment-derived Talaromycessp. SCSIO 41412. Compounds 1–3are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1–7were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB–ttpE). These p-terphenyls (1–7) and 36 marine-derived terphenyl analogues (8–43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1–5, 14, 17, 23, and 26showed notable activities with IC50values of 0.40–16 μM. The binding pattern of p-terphenyl inhibitors 1–3with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-β1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5–20 μM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.

A range of annealing treatments were implemented to regulate the microstructure and mechanical properties of Ti−6Al−4V forging. The results show that both the as-forged and as-annealed microstructures exhibit a bimodal structure composed of equiaxed primary αphase (αp) and transformed βphase (βt). With the increase of annealing temperature, the secondary α(αs) phase precipitates from the βphase. There is no obvious texture and the crystal orientation is uniformly distributed. Meanwhile, strength initially increases and then decreases, whereas ductility remains largely unaffected. The alloy annealed at 860 °C has an excellent combination of strength and ductility, due to the larger content of the fine αsphase. All fracture surfaces contain massive dimples, which is a typical ductile fracture feature. The characteristics of microcracks, microvoids, and kinked αp/αl(equiaxed αpand lamellar αphase) phases are found near the fracture.

An unprecedented di-seco-indole diterpenoid, peniditerpenoid A (1), and a rare N-oxide-containing indole diterpenoid derivative, peniditerpenoid B (2), together with three known ones (3–5), were obtained from the mangrove-sediment-derived fungus Penicilliumsp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A (1) inhibited lipopolysaccharide-induced NF-κB with an IC50value of 11 μM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitrostudies demonstrated that 1exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.

To discover novel osteoclast-targeting antiosteoporosis leads from natural products, we identified 40 tanzawaic acid derivatives, including 22 new ones (1–8, 14–19, 27–32, 37, and 38), from the South China Sea mangrove-derived fungus Penicillium steckiiSCSIO 41025. Penicisteck acid F (2), one of the new derivatives showing the most potent NF-κB inhibitory activity, remarkably inhibited osteoclast generation in vitro. Mechanistically, 2reduced RANKL-induced IκBα degradation, NF-κB p65 nuclear translocation, the activation and nuclear translocation of NFATc1, and the relevant mRNA expression. NF-κB p65 could be a potential molecular target for 2, which has been further determined by the cellular thermal shift assay, surface plasmon resonance, and the gene knock-down assay. Moreover, 2could also alleviate osteoporosis in ovariectomized mice by reducing the quantities of osteoclasts. Our finding offered a novel potential inhibitor of osteoclastogenesis and osteoporosis for further development of potent antiosteoporosis agents.

Protein S-acylation is a reversible post-translational modification (PTM). It is present on diverse proteins and has important roles in regulating protein function. Aminolysis with hydroxylamine is widely used in the global identification of the PTM. However, the identification is indirect. Distinct criteria have been used for identification, and the false discovery rate has not been addressed. Here, we report a site-specific method for S-acylation identification based on tagging of S-acylation sites with iodoTMT0. Efforts to improve the performance of the method and confidence of identification are discussed, highlighting the importance of reducing contaminant peptides and keeping the recovery rate consistent between aliquots with or without hydroxylamine treatment. With very stringent criteria, presumptive S-acylation sites of 269, 684, 695, and 780 were identified from HK2 cells, HK11 cells, mouse brain, and mouse liver samples, respectively. Among them, the newly identified protein S-acylation sites are equivalent to 34% of human and 24% of mouse S-acylation sites reported previously. In addition, false-positive rates for S-acylation identification and S-acylation abundances were estimated. Significant differences in S-acylation abundance were found from different samples (from 0.08% in HK2 cells to 0.76% in mouse brain), and the false-positive rates were significantly higher for samples with a low abundance of S-acylation.

Purpose: The mechanical behaviors of general microbeams are presented, including the lateral forced vibration of a symmetric straight microbeam subjected to transverse excitation and the buckling and postbuckling of a symmetric curved composite microbeam subjected to axial and thermal loads. Methods: To achieve this, the nonlocal elasticity theory is taken into account and the small scale parameter is involved to modeling the symmetric straight microbeam. The nonlinear partial differential equation governing microbeam lateral motion is derived due to the axial elongation, and a set of linear ordinary differential equations are derived by the method of multiple scales. The lateral displacement is determined and the amplitude-frequency relation is presented and discussed. Subsequently, the in-plane instability of functionally graded carbon nanotube reinforced composite curved microbeams in thermal environment is examined. Results: It is showed that an increase in carbon nanotube volume fraction improves the critical buckling load of the composite microbeams. The temperature-induced tensile loading and displacement also have remarkable effects. Furthermore, geometrical parameters can be used to determine the buckling mode of the composite microbeam due to its significant effect on critical buckling loads. Conclusions: The solutions of critical geometrical parameters are determined and they are affected by the temperature change, carbon nanotube distribution and volume fraction, respectively.

Intrauterine adhesions (IUA) refer to adhesions within the uterine cavity and cervix caused by injuries from uterine surgery. They are a significant cause of female infertility. Exosomes derived from mesenchymal stem cells (MSCs) play an active role in the treatment of IUA. However, the mechanism by which they reduce fibrosis in the damaged endometrium remains unclear. In this paper, we demonstrate that exosomes derived from placental mesenchymal stem cells (PMSCs) can restore uterine functions and improve the fertility rate of injured animals. This is achieved by promoting cell proliferation, increasing endometrial thickness, and reversing fibrosis. Regarding the molecular mechanism behind these therapeutic effects, we identify three specific miRNAs, namely, miR-125b-5p, miR-30c-5p, and miR-23a-3p, enriched in PMSC-exosomes, as the key players in the treatment of IUA. Specifically, miR-125b-5p/miR-30c-5p and miR-23a-3p inhibit the expression of smad2 and smad3 by targeting their 3′-untranslated regions, resulting in the downregulation of the transforming growth factor-β (TGF-β)/smad signaling pathway and the reversal of fibrosis. Notably, the safety of PMSC-exosomes in intrauterine treatment was also been confirmed. In conclusion, we illustrate that exosomes derived from PMSCs possess the capability to repair endometrial damage and enhance fertility in injured animals by regulating the TGF-β/smad pathway via miR-125b-5p, miR-30c-5p, and miR-23a-3p. This provides insights into the precision treatment of IUA through exosome-based cell-free therapy.

An NFC tag chip employing the ISO/IEC14443-A protocol is developed in SMIC $0.13\mu \text{m}$ EEPROM 2P6M CMOS process, boasting a chip area of $620.03\mu \text{m}\times 567.93\mu \text{m}$ and a power consumption of under $100\mu \text{W}$ . The chip addresses critical issues such as reducing power consumption and minimizing area costs for covering numerous IoT nodes. For a small area of the chip, a specialized ESD protection circuit is proposed, efficiently multiplexing discharge transistors, cross-gate connected rectifiers, limiters for overvoltage protection, and load switch modulators within the chip’s limited space. For power efficiency, a compact $175.44\mu \text{m}\times 32.98\mu \text{m}\,\,18.52\mu \text{A}$ LDO based on the current mirror and current feedback is presented for the DC supply during the 100% ASK modulation. Additionally, an ASK demodulator and a 13.56MHz±kHz clock generator are designed in compact areas of $62.19\mu \text{m}\times 56.06\mu \text{m}$ and $24.76\mu \text{m}\times 13.14\mu \text{m}$ , respectively. These components ensure stable protocol communication with digital circuits and support a 7kb EEPROM, providing a comprehensive solution for NFC-based IoT information collection.

In this work, we successfully constructed Mn-coordinated nitrogen–carbon nanoparticles (Mn–N–C NPs) exhibiting multienzyme-like activities. In a bacterial infectious microenvironment, the POD-like and OXD-like activities of Mn–N–C NPs could synergistically trigger the generation of ROS (OH and O2−), causing oxidative damage to the bacterial cell membrane for killing bacteria. Alternatively, in neutral or weak alkaline normal tissues, the excessive O2−could be converted into O2and H2O2viathe SOD-like ability of Mn–N–C NPs, and subsequently their CAT-like activity catalyzed excess H2O2into H2O and O2for protecting normal cells through the antioxidant defense. Mn–N–C NPs also possessed a good NIR-photothermal performance, which could enhance their POD-like and OXD-like activities. Furthermore, Mn–N–C NPs could facilitate the GSH oxidation process and disrupt the intrinsic balance in the bacterial protection microenvironment with the assistance of H2O2, which is beneficial for rapid bacterial death. Undoubtedly, the Mn–N–C NPs + H2O2system showed the highest antibacterial activity when irradiated with an 808 nm laser, destroying the bacterial membrane and causing the efflux of proteins. Moreover, the Mn–N–C NPs + H2O2system was immune to the development of bacterial resistance and could efficiently disrupt the formation of a bacterial biofilm with negligible cytotoxicity and low hemolysis ratio. Finally, Mn–N–C NPs exhibited an excellent antibacterial performance in vivoand could accelerate wound healing without cellular inflammation production. Therefore, due to their significant therapeutic effects, Mn–N–C NPs show great potential in fighting antibiotic-resistant bacteria.

ABSTRACT In order to study the dynamic behaviour and energy dissipation of reinforced recycled aggregate concrete (RAC) beams under impact, four groups of reinforced RAC simply supported beams with various [...]

ABSTRACT This paper presents the experimental and numerical investigations on the seismic behaviour of steel-jacket retrofitted reinforced concrete (SJRRC) columns with recycled aggregate concrete (RAC). An unstrengthened reinforced concrete (RC) [...]

We consider the problem of recovering the superposition of $R$distinct complex exponential functions from compressed non-uniform time-domain samples. Total variation (TV) minimization or atomic norm minimization was proposed in the literature to recover the $R$frequencies or the missing data. However, it is known that in order for TV minimization and atomic norm minimization to recover the missing data or the frequencies, the underlying $R$frequencies are required to be well separated, even when the measurements are noiseless. This paper shows that the Hankel matrix recovery approach can super-resolve the $R$complex exponentials and their frequencies from compressed non-uniform measurements, regardless of how close their frequencies are to each other. We propose a new concept of orthonormal atomic norm minimization (OANM), and demonstrate that the success of Hankel matrix recovery in separation-free super-resolution comes from the fact that the nuclear norm of a Hankel matrix is an orthonormal atomic norm. More specifically, we show that, in traditional atomic norm minimization, the underlying parameter values mustbe well separated to achieve successful signal recovery, if the atoms are changing continuously with respect to the continuously valued parameter. In contrast, for the OANM, it is possible the OANM is successful even though the original atoms can be arbitrarily close. As a byproduct of this research, we provide one matrix-theoretic inequality of nuclear norm, and give its proof using the theory of compressed sensing.

Single-atom catalysts (SACs), a novel kind of electrocatalysts with full metal utilization, have been developed as unique signal amplifiers in several sensing platforms. Herein, based on theoretical prediction of the oxygen reduction reaction (ORR) mechanism on different atom sites, we constructed dual-atomic-site catalysts (DACs), Fe/Mn–N–C, to catalyze luminol-dissolved oxygen electrochemiluminescence (ECL). Computational simulation indicated that the weak adsorption of OH* on a single Fe site was overcome by introducing Mn as the secondary metallic active site, resulting in a synergic dual-site cascade mechanism. The superior catalytic activity of Fe/Mn–N–C DACs for the ORR was proven by the highly efficient cathodic luminol ECL, surpassing the performance of single-site catalysts (SACs), Fe–N–C and Mn–N–C. Furthermore, the ECL system, enhanced by a cascade reaction, exhibited remarkable sensitivity to ascorbic acid, with a detection limit of 0.02 nM. This research opens up opportunities for enhancing both the ECL efficiency and sensing performance by employing a rational atomic-scale design for DACs.

ABSTRACT It is an effective solution to strengthen structural column by using steel jacket and infill concrete for reinforced concrete (RC) structure retrofitting. In this research, the recycled aggregate concrete [...]

2-Phenyl-1H-imidazole-1-sulfonate (PHIS) is used as an electrolyte additive, to scavenge H2O/HF and help to build a protective film on the interface of the electrodes/electrolyte, as a result, to enhance the high temperature performance of LiNi0.8Co0.1Mn0.1O2/graphite batteries.

Nowadays, as the vivid visual enjoyment requiring in mobile display devices exploding everywhere, enormous bandwidth pressure lands in all high-speed digital transmission interfaces, such as HDMI, MIPI, DP, eDP etc. A low latency in pixels’ time, flexible implementation for circuits, and high performance in visual quality video stream encoder and decoder (FHP-Codec) is proposed to relax the stress. The image structural features are analyzed, which directs an accurate 1D or 2D prediction reducing the redundancy utmost compared with DSC by 10~20% benefit in entropy, without obvious increments in circuit area and power consumption. According to the benchmark in Kodak image suite, FHP-Codec shows a considerable cost-performance ratio for display driver application fields.

Mura artifacts reduction (De‐Mura) processing, with a high performance for low grayscales, is developed and integrated in display drivers for active‐matrix organic light‐emitting diode (AMOLED) display. The proposed De‐Mura processing, designed to compensate an AMOLED panel's luminance Mura (L‐Mura) and color Mura (C‐Mura), shows excellent display performance, and the major display properties include a diminished luminance non‐uniformity under low grayscales (<= Gray 16) and low luminous brightness (<= 2 cd/m 2), and an improved visually imperceptible color non‐uniformity. Our works reveals an effective solution to work around the inevitable difficulties of optical measurement of AMOLED panels under low luminous brightness.

Background: The role of laparoscopic-assisted natural orifice specimen extraction (LA-NOSE) colectomy in the treatment of left-sided colon cancer has not been well defined, and there remains confusion about how to conveniently exteriorize specimens through natural orifices. Therefore, we introduced a homemade invention, the Cai tube, to facilitate the extraction of specimens and compared the clinical outcomes of LA-NOSE with conventional laparoscopic (CL) colectomy for left-sided colon cancer. Methods: From March 2015 to August 2017, patients with left-sided colon cancer were randomly divided into LA-NOSE and CL groups. Specimens were extracted through the anus with the help of a Cai tube (Patent Number: ZL201410168748.2) in the LA-NOSE group. The primary outcome measure was postoperative pain. Secondary outcomes were the duration of operation, postoperative recovery, surgical morbidity, pathological quality of the specimen, and long-term outcomes, including 3-year overall survival, disease-free survival, local recurrence, and overall recurrence. Results: A total of 60 patients (30 per group) were recruited for this study. None of the patients required emergency conversion to conventional laparoscopic or open surgery during the operation. The postoperative maximum pain score was significantly lower in the LA-NOSE group (mean 2.5 vs. 5.1,P= 0.001), as was the additional analgesia requirement (mean 2/30 vs. 10/30,P= 0.021). Patients in the LA-NOSE group experienced a shorter first time to passage of flatus (mean 2.2 vs. 3.1 days, P= 0.026). All patients could control their defecation at 6 months after surgery. The comparison between the two groups showed no significant differences in the operative time, bleeding volume, postoperative hospital stay, surgical morbidity rates, number of lymph nodes harvested, or resection margin status. The mean follow-up was 48 months (range 7–59) and was similar in both groups. The results showed no differences in long-term outcomes between the two groups. Conclusion: In the treatment of left-sided colon cancer, compared with conventional laparoscopic colectomy, LA-NOSE colectomy using the Cai tube exhibited lower postoperative pain, shorter recovery of gastrointestinal function, and similar long-term outcomes. Registration number: ChiCTR-OOR-15007060 (http://www.chictr.org.cn/).

The technology of fan-out wafer level packaging (FOWLP) has been widely adopted for millimeter wave Antenna-in-Package (AiP) system integration with low interconnection parasitic parameters. Present AiP solutions using FOWLP technology generally form antenna pattern on Redistribution Layer, which brings design inconvenience. In our work, a low-cost PCB antenna with relatively large size is integrated, forms three-dimensional stacked structure. The AiP employs right angle transition board embedded in Epoxy molding compound (EMC), which transmits mm-wave signal to the substrate-integrated waveguide (SIW) antenna stacked on the back of EMC. The SIW antenna consists of 4x4 radiation slots with modified magnetoelectric dipole for bandwidth enhancement. Measured gain is 14dBi at 60GHz with bandwidth beyond 55-65GHz. The SIW antenna works also as heat sink, no extra thermal design is needed for 0.5W power consumption. The AiP module is manufactured and measured on circuit board. The proposed approach is a convenient solution for wide band and high gain millimeter wave AiP system integration.

Aiming at the limitations of current fixed charging facilities and considering the charging needs of users in multiple scenarios, a mobile charging complex with real-time monitoring of rest, consumption and charging safety has been developed to meet the needs of users in multiple scenarios. Firstly, according to the development status of mobile charging, the technical route of mobile charging complex is proposed and the functions and requirements of the complex are clarified. Secondly, the mobile charging complex device that can be used in multiple scenarios such as high-speed service areas, residential areas and so on. A mobile charging integrated cabin, a charging cabin and a rest cabin are respectively designed. And the functional composition and commercial promotion value of each cabin are researched, which has been applied in Quzhou service area of G60 Shanghai–Kunming expressway in Zhejiang, China. Finally, the development of mobile charging complex is prospected from the perspectives of ergonomics, demand response, intelligent parking and bionic charging arm. Through the practical application, it is verified that the technical solution can effectively reduce the operation and maintenance cost of charging facilities under the premise of safety and reliability. It realizes peak shaving and valley filling, which is conducive to the healthy and stable development of charging facilities.

In this paper, we present a new color space model for AMOLED display based on IR drop. This paper discusses the relationship between the color space and the IR drop of AMOLED display, then derives the corresponding color space model. Based on this model, the level of IR Drop can be adaptively adjusted to change the color space of the panel, to accurately display the brightness and chroma of target. In the experimental results, it is confirmed that the native color space of the panel can be auto tuned to less than 0.5 on average in CIEDE2000 for different target color spaces in different applications. In addition, a corresponding fast calibration method within 15 seconds has been developed to match with our driver chips, to be applied to individual panel correction and calibration requirements in a production line.

Stylocarotid artery syndrome (SAS) is a rare variant of Eagle’s syndrome that may lead to transient ischemic attack or stroke. The underlying pathophysiological mechanism involves compression of the internal carotid artery by an elongated styloid process (ESP), potentially resulting in vascular occlusion or dissection. An ESP exceeding 2.5 cm is deemed elongated, with a length of 3.0 cm considered clinically significant. Although the prevalence of ESP ranges from 4.0% to 7.3%, symptomatic cases are rare; symptoms are present in only approximately 4.0% of individuals with an ESP. Unlike the typical symptoms of Eagle’s syndrome, SAS may not cause pharyngeal discomfort, the sensation of a foreign body in the throat, dysphagia, or facial pain. This absence of characteristic symptoms as well as the development of central nervous system symptoms often leads patients to seek care from neurologists instead of otolaryngologists, increasing the likelihood of misdiagnosis or underdiagnosis. We herein report a unique case of ischemic stroke caused by SAS and present a literature review on cases of SAS-associated ischemic stroke published in the past decade. The reporting of this study conforms to the CARE guidelines.

In a 2 yr field experiment, we investigated the combined effects of reduced nitrogen (N) rate and increased plant density on the trade-off between the grain protein content (GPC) and the grain yield (GY) in soft wheat cultivars. Reducing N application significantly decreased both GPC and GY; however, to some extent, increasing the top-dressed N ratio and plant density compensated for the GY loss. Optimizing the combination of these three factors (150 kg N ha–1with 50% top-dressed N and 360 × 104plants ha–1) achieved both the required lower GPC for soft wheat and relatively higher GY compared with the conventional cultivation strategy. In addition, this optimized combination downregulated 11 high-molecular-weight glutenin subunits, 8 low-molecular-weight glutenin subunits, 5 α/β-gliadins, and 2 γ-gliadins in mature grains as identified by data-independent acquisition mass spectrometry. Further analysis indicated that the relatively lower free amino acid content and downregulated expressions of the seed storage protein (SSP) synthesis-related genes in filling grains contributed to the reduction of SSP and GPC. Furthermore, the dilution effect induced by a relatively higher accumulation of starch than proteins also partially explained the reduced GPC. Unlike proteins, grain starch accumulation and content depended more on the soluble sugar availability, rather than on the starch synthesis capacity. These findings provide novel insights on simultaneous improvement in the grain quality and yield of soft wheat through synchronized manipulations of N fertilization and plant density.

The Omicron (B.1.1.529) variant of SARS-CoV-2 emerged in November 2021 and is rapidly spreading among the human population1. Although recent reports reveal that the Omicron variant robustly escapes vaccine-associated and therapeutic neutralization antibodies2–10, the pathogenicity of the virus remains unknown. Here we show that the replication of Omicron is substantially attenuated in human Calu3 and Caco2 cells. Further mechanistic investigations reveal that Omicron is inefficient in its use of transmembrane serine protease 2 (TMPRSS2) compared with wild-type SARS-CoV-2 (HKU-001a) and previous variants, which may explain its reduced replication in Calu3 and Caco2 cells. The replication of Omicron is markedly attenuated in both the upper and lower respiratory tracts of infected K18-hACE2 mice compared with that of the wild-type strain and Delta (B.1.617.2) variant, resulting in its substantially ameliorated lung pathology. Compared with wild-type SARS-CoV-2 and the Alpha (B.1.1.7), Beta (1.351) and Delta variants, infection by Omicron causes the lowest reduction in body weight and the lowest mortality rate. Overall, our study demonstrates that the replication and pathogenicity of the Omicron variant of SARS-CoV-2 in mice is attenuated compared with the wild-type strain and other variants.

Highly pathogenic coronaviruses, including severe acute respiratory syndrome coronavirus 2 (refs. 1,2) (SARS-CoV-2), Middle East respiratory syndrome coronavirus3(MERS-CoV) and SARS-CoV-1 (ref. 4), vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture5–7and in patient tissues8–10, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that caspase-6, a cysteine-aspartic protease of the apoptosis cascade, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid proteins, generating fragments that serve as interferon antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss in golden Syrian hamsters infected with SARS-CoV-2 and improves the survival of mice expressing human DPP4 that are infected with mouse-adapted MERS-CoV. Our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivoactive. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses(SARS-CoV-1 and SARS-CoV-2), Merbecovirus(MERS-CoV), as well as the Alphacoronavirus(hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.

High‐performance Mura artifact reduction (De‐Mura) processing is developed and integrated in display drivers for raising panel yield. The proposed De‐Mura processing, designed to compensate an active‐matrix organic light‐emitting diode (AMOLED) panel's luminance Mura (L‐Mura) and color Mura (C‐Mura), shows excellent display performance, and the major display properties include a diminished luminance nonuniformity from about 50% to about 10% under different gray levels, and an improved visually imperceptible color nonuniformity. Among 500 pieces of 5.83” (1128×2436, 460 PPI) retina AMOLED panels, panel yield is improved up to 96.8%. Our works reveals an effective external De‐Mura solution integrated in display drivers for panel factories and module suppliers to obtain high panel yield.

ABSTRACTBackgroundCOVID-19 vaccination has been accepted widely. However, there are only a few reports on patients’ willingness to be vaccinated. This study investigated the willingness of Chinese outpatients to accept COVID-19 vaccination as well as influencing factors.MethodsA cross-sectional survey was conducted in Jiangsu province, China in December 2020. Self-administered questionnaires, which were distributed to 625 outpatients among secondary hospitals, addressed demographic characteristics, sociological characteristics, and subjective reasons. There were 522 (83.5%) participants who gave completely valid responses. Logistic regression analysis was performed to explore the risk factors for willingness of COVID-19 vaccination.Results71.5% of participants were willing to receive the COVID-19 vaccine. “worried about contracting COVID-19” (49.6%) and “vaccines have just been introduced and need time to consider” (38.9%) were the main reasons for being willing and unwilling to receive COVID-19 vaccine, respectively. The logistic regression analysis showed that “vaccines are an effective way to prevent diseases” (OR = 5.07, 95%CI: 3.32–7.75), “the price you are willing to pay for non-free vaccines (yuan) (101–500 vs ≤100)″ (OR = 1.87, 95%CI: 1.16–3.02), “per capital monthly income(yuan) (>6000 vs ≤3000)”(OR = 2.13, 95%CI: 1.03–4.41), and “self- assessed health status (Good vs Bad)″ (OR = 1.71, 95%CI: 1.01–2.90) were the main risk factors for outpatients to be willing to receive the COVID-19 vaccine.ConclusionsThe willingness of Chinese outpatients to receive COVID-19 vaccine was not high. The government should do more to increase publicity of knowledge about COVID-19 vaccine thus increasing willingness to vaccinate, and provide free vaccine to eliminate the cost impact.

Drought priming is a promising approach to improve tolerance to further drought in wheat. The root apex plays important roles in drought however, its contribution to drought priming remains unknown. To provide mechanistic insights into this process, the transcriptomes and proteomes at three different zones along the root axis under drought stress were analyzed. Physiological assessment of root growth indicated that priming augmented roots growth in response to drought and also the levels of protective proline and glycine betaine. Scanning across the proximal to the distal zones of the root apex indicated increases the transcription of genes involved in primary and secondary metabolism. Conversely, genes related to translation, transcription, folding, sorting and degradation, replication and repair were increased in the apex compared to the proximal zone. A single drought episode suppressed their expression but prior drought priming served to maintain expression with recurrent drought stress. The differentially primed responses genes were mainly involved in the pathways related to plant hormone signaling, stress defense and cell wall modification. The prediction of regulatory hubs using Cytoscape implicated signaling components such as the ABA receptor PYL4 as influencing antioxidant status and the cell cycle. Based our integrative transcriptomic-proteomic assessments we present a model for drought priming protected plant hormone signaling transduction pathways to drive the cell cycle and cell wall loosening to confer beneficial effects on roots to counter the effects of drought. This model provides a theoretical basis for improvement of drought tolerance in wheat, via an increased understanding of drought priming induced drought tolerance.

The forming process of wire and arc additively manufacture (WAAM) was studied using the self-developed and designed WAAM system. The single-pass and single-layer weld bead samples were prepared with different process parameters, and the cross-sectional dimensions of the weld bead were measured. The influence rules of weld current, welding speed, wire feed speed and welding height on the weld bead size were obtained. In addition, the overlap experiment of the WAAM forming process was also carried out. The multiple and multilayer lap samples with different overlap rates were prepared, and the cross-sections of the lap samples were observed and analyzed. Finally, the overlap rate range of 35-45% with good forming effect was obtained.

The plastic deformation mechanism of Ti-55531 alloy with bimodal microstructure was investigated by compression testing at room temperature. The bimodal microstructure was composed of equiaxed primary α phase (αp) and transformed β (βtrans) that consisted of acicular secondary α phase (αs) and residual β phase (βr). In the initial stage of deformation, the αp grains first underwent plastic deformation, the dislocations germinated and increased, forming the dislocation loop with the dislocation free zone in αp at the true stain of 0.083. With the true strain subsequently increasing to 0.105, the dislocation tangle and dislocation pile-up occurred in αp, and a lot of dislocations were also activated in most of αs. Moreover, the dislocation density was increasing gradually in βr with the adding of strain. Finally, the dislocation pile-up and dislocation tangle appeared in αs and βr at the true strain of 0.163. The whole deformation process was coordinated by αp, αs and βr. They accommodated mutually and completed deformation together.

ABSTRACTIntroduction: Cytochrome P450 (CYP) is a monooxygenase superfamily mediating the elimination of anti-hypertensive drugs. Polymorphisms of CYP would lead to differential drug efficacy. Building relationships between genotype and phenotype will benefit individual medical treatment of hypertension.Areas covered: The review systematically summarizes the polymorphisms of four CYPs (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) concentrated distributed in the Han Chinese population. Moreover, the activity of variants on metabolizing anti-hypertensive drugs are reviewed, especially drugs with adrenoceptor blocking properties, as well as their clinical relevancies.Expert opinion: The polymorphisms of CYP can cause stratification in drug exposure of antihypertensive drugs. Although the clinical relevance has been built partially, the translational medicine still lacks reliable data support. Furthermore, the studies have demonstrated that even the same CYP variant will exhibit different catalytic capability for different drugs, which is another obstacle to hinder its application. With the deepening of multiomics research and structural biology, nucleotide polymorphisms can be combined with transcriptome, proteome, metabolome and molecular structure analyses to study the susceptibility to hypertension and drug efficacy. A complete data chain would be further estabolished by combining studies of pharmacokinetics-pharmacodynamics, which can effectively promote the precise application of anti-hypertensive drugs.

The impact of drought stress on crop yield and quality is substantial. Drought priming during the early growth stage of plants has been shown to improve tolerance to drought stress during the reproductive stage, although its effects on grain quality remains elusive. This study aimed to investigate the influence of drought priming on starch and protein levels in grains under drought stress during grain filling. Our results reveal that drought stress results in a reduction in starch content and its constituents, while simultaneously increasing glutenin macropolymers and protein fractons. Notably, drought primed plants under drought stress (PD) exhibit mitigated declines in starch content and its components, leading to improvements in starch swelling power and pasting properties. Additionally, PD results in a slight increase in protein fractions, limiting the overall rise in total protein content compared to drought stress alone. Collectively, our study underscores the efficacyof drought priming as a strategy to counteract the negative effects of drought stress on grain quality, particularly by minimizing starch losses and restraining protein content elevation.

Biogenic amine (BA) is a class of nitrogen-containing small molecular organic compounds with biological activity. Excessive BAs in wine affect flavor and quality of wine and are hazardous to human health. However, little attention has been paid to the effect of non-Saccharomycesyeasts and Saccharomyces cerevisiaemixed fermentation on BAs in white wine. The effect of mixed fermentation on BAs and amino acids in wine was investigated using two white grapes of Sauvignon Blanc and Gewürztraminer. Higher levels of total amino acids and BAs in Gewürztraminer wine compared to Sauvignon Blanc wine may be due to different grape varieties. Mixed fermentation did not influence BA profiles in Sauvignon Blanc wine, while it increased total BAs content. VL3 (VL) fermented wine has 33.7% less BAs content than EC1118 (EC) single-strain fermented wine. Similar phenomenon was found in Gewürztraminer wine produced by different fermentation combinations except that cadaverine was only detected in wine produced by Hanseniaspora uvarumparticipated in mixed fermentations. Principal coordinate analysis (PCoA) and permutational multivariate analysis of variance (PERMANOVA) revealed that the effects on BAs were related to grape varieties and yeast species in white wine. Ethanolamine, tryptamine, isoamylamine and histamine content in wine were related to grape varieties. Collectively, mixed fermentation increased BAs content in Sauvignon Blanc and Gewürztraminer wine. The content of BAs in wine fermented by VL single-strain fermentation was lower than that fermented by EC single-strain fermentation, which is more suitable for the winemaking of white wine.

This study aims to examine the relationship between dyadic coping (DC), intimate relationship, and quality of life (QOL), and to explore the mediating role of intimate relationship in patients with breast cancer (BC) and their spouses from a dyadic perspective.

Frequent drought events especially those occur in the reproductive stages severely restrict global crop productivity. Moderate drought priming during the earlier growth stages is a promising strategy for plants to resist to recurrent severe drought stress. However, the underlying mechanisms remain unclear. Here, we subjected wheat plants to drought priming during the vegetative growth stage and to severe drought stress at 10 days after anthesis. We then collected leaf samples at the ends of the drought priming, recovery periods, and at the ends of drought stress for transcriptome sequencing in combination with phenotypic and physiological determination. The drought-primed wheat plant maintained a lower plant temperature, with higher stomatal openness and photosynthesis, thereby resulting in much less 1,000-grain weight and grain yield losses under the later drought stress than the non-primed plants. Interestingly, 416 genes of which 27 transcription factors (e.g., MYB, NAC, HSF) seemed to be closely related to the improved drought tolerance as indicated by the dynamic transcriptome analysis. Moreover, the candidate genes showed six temporal expression patterns and significantly enriched in several stress response related pathways such as plant hormone signal transduction, starch and sucrose metabolism, arginine and proline metabolism, inositol phosphate metabolism, and wax synthesis. These findings illustrate new insights into physiological and molecular mechanisms of the long-term effects of early drought priming to effectively improve drought tolerance in wheat, which proved potential approaches to challenge the increasing abiotic stresses and secure food safety under global warming scenarios.

Drought stress is a limiting factor for wheat production and food security. Drought priming has been shown to increase drought tolerance in wheat. However, the underlying mechanisms are unknown. In the present study, the genes encoding the biosynthesis and metabolism of abscisic acid (ABA) and jasmonic acid (JA), as well as genes involved in the ABA and JA signaling pathways were up-regulated by drought priming. Endogenous concentrations of JA and ABA increased following drought priming. The interplay between JA and ABA in plant responses to drought priming was further investigated using inhibitors of ABA and JA biosynthesis. Application of fluridone (FLU) or nordihydroguaiaretic acid (NDGA) to primed plants resulted in lower chlorophyll-fluorescence parameters and activities of superoxide dismutase and glutathione reductase, and higher cell membrane damage, compared to primed plants (PD) under drought stress. NDGA + ABA, but not FLU + JA, restored priming-induced tolerance, as indicated by a finding of no significant difference from PD under drought stress. Under drought priming, NDGA induced the suppression of ABA accumulation, while FLU did not affect JA accumulation. These results were consistent with the expression of genes involved in the biosynthesis of ABA and JA. They suggest that ABA and JA are required for priming-induced drought tolerance in wheat, with JA acting upstream of ABA.

The vehicle axle is the main bearing part of the vehicle transmission, which needs to carry large power and torque. The axle is processed with high-strength steel. In order to verify the material properties of the axle and confirm whether it meets the design requirements, the chemical composition, mechanical properties, microstructure and metal inclusions of the axle are analyzed. The results show that the chemical composition of the material used in the axle meets the standard requirements, the parts with high hardness and tensile strength are tempered martensite, and the metal inclusions are mainly alumina inclusions, silicate inclusions and tin inclusions. Through the analysis of the performance of the axle, it is concluded that the axle material can meet the design requirements.

Carbon materials have shown remarkable usefulness in facilitating the performance of insulating sulfur cathode for lithium–sulfur batteries owing to their excellent conductivity and porous structure. However, the anxiety is the poor affinity toward polar polysulfides due to the intrinsic nonpolar surface of carbon. Herein, we report a direct pyrolysis of the mixture urea and boric acid to synthesize B/N–codoped hierarchically porous carbon nanosheets (B–N–CSs) as efficient sulfur host for lithium–sulfur battery. The graphene–like B–N–CSs provides high specific surface area and porous structure with abundant micropores (1.1 nm) and low–range mesopores (2.3 nm), thereby constraining the sulfur active materials within the pores. More importantly, the codoped B/N elements can further enhance the polysulfide confinement through strong Li–N and B–S interaction based on the Lewis acid–base theory. These structural superiorities significantly suppress the shuttle effect by both physical confinement and chemical interaction, and promote the redox kinetics of polysulfide conversion. When evaluated as the cathode host, the S/B–N–CSs composite displays the excellent performance with a high reversible capacity up to 772 mA h g–1at 0.5 C and a low fading rate of ~0.09% per cycle averaged upon 500 cycles. In particular, remarkable stability with a high capacity retention of 87.1% can be realized when augmenting the sulfur loading in the cathode up to 4.6 mg cm–2.

A novel coronavirus—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—emerged in humans in Wuhan, China, in December 2019 and has since disseminated globally1,2. As of April 16, 2020, the confirmed case count of coronavirus disease 2019 (COVID-19) had surpassed 2 million. Based on full-genome sequence analysis, SARS-CoV-2 shows high homology to SARS-related coronaviruses identified in horseshoe bats1,2. Here we show the establishment and characterization of expandable intestinal organoids derived from horseshoe bats of the Rhinolophus sinicusspecies that can recapitulate bat intestinal epithelium. These bat enteroids are fully susceptible to SARS-CoV-2 infection and sustain robust viral replication. Development of gastrointestinal symptoms in some patients with COVID-19 and detection of viral RNA in fecal specimens suggest that SARS-CoV-2 might cause enteric, in addition to respiratory, infection3,4. Here we demonstrate active replication of SARS-CoV-2 in human intestinal organoids and isolation of infectious virus from the stool specimen of a patient with diarrheal COVID-19. Collectively, we established the first expandable organoid culture system of bat intestinal epithelium and present evidence that SARS-CoV-2 can infect bat intestinal cells. The robust SARS-CoV-2 replication in human intestinal organoids suggests that the human intestinal tract might be a transmission route of SARS-CoV-2.

TA29 titanium alloy forging was heated by duplex annealing. The fatigue crack growth behaviour of the alloy at room temperature, 400 °C, 500 °C and 600 °C was studied. The relationship between the fatigue crack growth rate (Da/dN) and the stress intensity factor amplitude (△K) of TA29 alloy at different temperatures was revealed by Paris formula. The fatigue fracture morphology of fatigue crack growth specimens was analysed by scanning electron microscopy (SEM). The results showed that the TA29 titanium exhibited good crack growth resistance at room temperature. With the increase of test temperature, the C value of the Paris formula increased, the m value decreased, and the fatigue crack growth rate increased. From the fatigue fracture morphology of the specimens, it was found that the fractures of fatigue crack growth specimens at different temperatures exhibited typical pre-splitting zone, steady-state expansion zone and rapid expansion zone. As the temperature increased, the range of the pre-cracking zone was larger, the range of the steady-state extension zone and the rapid expansion zone were smaller. At room temperature, there was no obvious fatigue strips in the steady-state expansion zone, and the transient fracture zone exhibited the characteristics of cleavage fracture, while the steady-state expansion zone at high temperature showed obvious fatigue strips and secondary cracks, and the transient fracture zone was a typical ductile fracture mechanism.

Understanding the contribution of protein composition and gluten structure to dough property and biscuit baking is crucial to improve soft wheat (Triticum aestivumL.) grain quality. Thus, the relationships of protein composition, gluten structure, and dough rheological properties with short biscuits quality was investigated using 10 Chinese soft wheat varieties. Content of grain protein, flour protein, gliadin, glutenin, and high and low molecular weight glutenin subunits were significantly positively correlated with hardness of biscuit, but negatively correlated with spread factor and sensory score. Gluten of wheat varieties with lower dough strength and better biscuit quality showed thinner walls of apertures and more regular apertures in its microstructure. The gluten with higher strength had more apertures and antiparallel β‐sheets and fewer α‐helices. Moreover, dough with a higher softening degree was easier to stretch and tended to produce biscuits with larger diameter and crispier taste during baking. In conclusion, main wheat quality characteristics that can be used to select grain samples suitable for making tasty biscuits were recommended as follows: flour protein content, wet gluten content and microstructure, Zeleny sedimentation value, and dough softening degree.

An ongoing outbreak of pneumonia associated with a novel coronavirus was reported in Wuhan city, Hubei province, China. Affected patients were geographically linked with a local wet market as a potential source. No data on person-to-person or nosocomial transmission have been published to date.

The exploration of efficient host materials of sulfur is significant for the practical lithium-sulfur (Li-S) batteries, and the hosts are expected to be highly conductive for high sulfur utilization and exhibit strong interaction toward polysulfides to suppress the shuttle effect for long-lasting cycle stability. Herein, we propose a simple synthesis of metallic cobalt-embedded N-doping carbon nanotubes (Co@NCNT) as a “two-in-one” host of sulfur for efficient Li-S batteries. In the binary host, the N-doped CNTs, cooperating with metallic Co nanoparticles, can serve as 3D conductive networks for fast electron transportation, while the synergetic effect of metallic Co and doping N heteroatoms helps to chemically confine polysulfides, acting as active sites to accelerate electrochemical kinetics. With these advantages, the S/Co@NCNT composite delivers an excellent cycling stability with a capacity decay of 0.08% per cycle averaged within 500 cycles at a current density of 1 A g–1and a high rate performance of 530 mA h g–1at 5 A g–1. Further, the superior electrochemical performance of the S/Co@NCNT electrode can be maintained under a high sulfur loading up to 4 mg cm–2. Our work demonstrates a feasible strategy to design promising host materials simultaneously featuring high conductivity and strong confinement toward polysulfides for high-performance Li-S batteries.