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The COVID-19 pandemic caused by SARS-CoV-2 remains a global public health threat and has prompted the development of antiviral therapies. Artificial intelligence may be one of the strategies to facilitate drug development for emerging and re-emerging diseases. The main protease (M pro ) of SARS-CoV-2 is an attractive drug target due to its essential role in the virus life cycle and high conservation among SARS-CoVs. In this study, we used a data augmentation method to boost transfer learning model performance in screening for potential inhibitors of SARS-CoV-2 M pro . This method appeared to outperform graph convolution neural network, random forest and Chemprop on an external test set. The fine-tuned model was used to screen for a natural compound library and a de novo generated compound library. By combination with other in silico analysis methods, a total of 27 compounds were selected for experimental validation of anti-M pro activities. Among all the selected hits, two compounds (gyssypol acetic acid and hyperoside) displayed inhibitory effects against M pro with IC50 values of 67.6 μM and 235.8 μM, respectively. The results obtained in this study may suggest an effective strategy of discovering potential therapeutic leads for SARS-CoV-2 and other coronaviruses.

In recent years, laparoscopic surgery and robotic surgery have been widely used, and various intraoperative image navigation systems have also developed rapidly. However, the liver itself has a complex vessel and duct system, which increase the difficulty of liver surgery. The augmented reality image navigation system combines the three-dimensional reconstructed image of the liver with the real liver anatomy, which presents the specific relationship between the tumor location and the surrounding vessels for the surgeon. Compared with other intraoperative image navigation methods, augmented reality has its unique advantages. This paper provides an overview of current advances in registration technology in augmented reality image navigation system, and focuses on its applications in liver surgery, including laparoscopic surgery and robotic surgery. Finally, the technological problems and difficulties still faced at present are summarized, and future directions worth studying in this field are proposed.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with anti-diabetic properties. Notably, the protective mechanism of the single peptide SWGEDWGEIW (TSP) from soybean peptides (SBPs) on insulin resistance of adipocytes in an inflammatory state was investigated by detecting the lipolysis and glucose absorption and utilization of adipocytes. The results showed that different concentrations of TSP (5, 10, 20 µg/mL) intervention can reduce 3T3-L1 adipocytes' insulin resistance induced by inflammatory factors in a dose-dependent manner and increase glucose utilization by 34.2 ± 4.6%, 74.5 ± 5.2%, and 86.7 ± 6.1%, respectively. Thus, TSP can significantly alleviate the lipolysis of adipocytes caused by inflammatory factors. Further mechanism analysis found that inflammatory factors significantly reduced the phosphorylation (p-Akt) of Akt, two critical proteins of glucose metabolism in adipocytes, and the expression of GLUT4 protein downstream, resulting in impaired glucose utilization, while TSP intervention significantly increased the expression of these two proteins. After pretreatment of adipocytes with PI3K inhibitor (LY294002), TSP failed to reduce the inhibition of p-Akt and GLUT4 expression in adipocytes. Meanwhile, the corresponding significant decrease in glucose absorption and the increase in the fat decomposition of adipocytes indicated that TSP reduced 3T3-L1 adipocytes' insulin resistance by specifically activating the p-Akt/GLUT4 signal pathway. Therefore, TSP has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

Local-regional therapy combined with PD-1 inhibitors and lenvatinib (triple combination therapy) has demonstrated potent antitumor activity in solid tumors. However, the efficacy and safety of the triple combination therapy in patients with advanced biliary tract cancer (BTC) remain unclear. This retrospective study evaluated the efficacy and safety of the triple combination therapy in advanced BTC. Tumor tissues were collected to assess the expression status of PDL1 to identify efficacy biomarkers. Forty-nine patients were included: 24 in lenvatinib plus toripalimab therapy; 25 in the triple combination therapy. The triple combination therapy group showed longer median progression-free survival (mPFS) (7.9 versus 5.6 months, P=0.015) and longer median overall survival (mOS) (13.7 versus 11.1 months, P=0.145) than the lenvatinib plus toripalimab group. The overall response rate (ORR) was 32% [95% confidence interval (CI): 12.3-51.7] with the triple combination therapy versus 25% (95% CI: 6.3-43.7) with toripalimab plus lenvatinib. Three patients received surgery after the triple combination therapy. All patients experienced any-grade adverse events (AEs) without any specific toxicities. PDL1 expression was associated with improved clinical benefits. Local-regional therapy combined with PD-1 inhibitors and lenvatinib may be an encouraging treatment choice for advanced BTC without an increase in specific toxicities., Competing Interests: None., (AJCR Copyright © 2023.)

The combination of immunotherapy and lenvatinib has shown a good response for inoperable hepatocellular carcinoma (HCC) patients. However, a specific marker to predict the response, overall survival (OS) and progression-free survival (PFS) of this combination treatment is lacking. The present work focused on investigating whether subcutaneous adipose tissue (SAT) characteristics on CT could predict the response and survival for HCC patients who receive the combination treatment. This study retrospectively enrolled 100 patients with inoperable HCC who received lenvatinib combined with anti-PD-1 antibody treatment from 2018 to 2022. Fifty-six patients were finally included. The area and density of SAT were measured using unenhanced cross-sectional CT images. The SAT volume index was calculated as the SAT area divided by height squared in meters (cm 2 /m 2 ). We classified these patients into two groups according to SAT volume index and density. Twenty-one patients (37.5%) with a low SAT volume index and high density were divided into the high risk group. High risk patients showed a markedly decreased objective response rate (ORR) compared with low risk patients (19.0% versus 54.3%, P = 0.021). The median PFS times were 6.00 and 12.03 months for the high risk and low risk groups, respectively (hazard ratio (HR) = 2.296, P = 0.035). High risk patients with Barcelona Clinic Liver Cancer (BCLC) stage-C had a markedly decreased OS of compared to low risk patients (HR = 4.272, P = 0.01). Patients with low SAT volume index and high density were found to have less opportunity to benefit from this combination therapy., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Short-term outcomes of laparoscopic hepatectomy of central-located liver lesions (LHCL) compared with traditional open hepatectomy of central-located liver lesions (OHCL) remain unclear. The aim of this study was to explore the safety and efficacy of LHCL., Methods: A retrospective analysis was performed on 262 patients who underwent hepatectomies involving resections of liver segment II, IV or VIII from January 2015 to June 2021 in two institutions. Patients in the LHCL group were matched in a 1:2 ratio to patients in the OHCL group., Results: After propensity score-matched (PSM) analysis, 61 patients remained in the LHCL group and 122 patients were in the OHCL group. What needs to be mentioned is that although not significant, patients in the OHCL group had increased lesion size (4.3 vs. 3.6 cm, p = 0.052), number (single/multiple, 84.8%/15.2% vs. 93.4%/6.6%, p = 0.097), and number of liver segments involved (one/two/three, 47.3%/42.0%/10.7% vs. 57.4%36.1%/10.7%, p = 0.393). To ensure surgical safety, fewer patients in the LHCL group underwent vascular exclusion than those in the OHCL group ( p = 0.004). In addition, LHCL was associated with lower blood loss ( p = 0.001) and transfusion requirement ( p = 0.004). In terms of short-term outcomes, the LHCL group had significantly lower levels of peak ALT ( p < 0.001), peak DBIL ( p = 0.042), peak PT ( p = 0.012), and higher levels of bottom ALB ( p = 0.049). Moreover, the LHCL group demonstrated quicker postoperative recovery, which was represented by shorter time to first flatus, time to oral intake, time to drain off, and hospital stay (all p < 0.001). Importantly, the LHCL group had a significantly reduced occurrence of postoperative complications ( p < 0.001) and similar R0 resection rates ( p = 0.678) when compared to the OHCL group., Conclusion: LHCL is associated with increased safety and better perioperative outcomes and thus could be recommended for patients with central space-occupying liver lesions when appropriately selecting the surgical procedure according to the total tumor burden and carefully handled by experienced surgeons. From the experience of our center, LHCL could be performed to solitary lesion involving liver segment IV/V/VIII, <5 cm, with good safety and feasibility.

In this paper, we propose a method to generate multi-depth phase-only holograms using stochastic gradient descent (SGD) algorithm with weighted complex loss function and masked multi-layer diffraction. The 3D scene can be represented by a combination of layers in different depths. In the wave propagation procedure of multiple layers in different depths, the complex amplitude of layers in different depths will gradually diffuse and produce occlusion at another layer. To solve this occlusion problem, a mask is used in the process of layers diffracting. Whether it is forward wave propagation or backward wave propagation of layers, the mask can reduce the occlusion problem between different layers. Otherwise, weighted complex loss function is implemented in the gradient descent optimization process, which analyzes the real part, the imaginary part, and the amplitude part of the focus region between the reconstructed images of the hologram and the target images. The weight parameter is used to adjust the ratio of the amplitude loss of the focus region in the whole loss function. The weight amplitude loss part in weighted complex loss function can decrease the interference of the focus region from the defocus region. The simulations and experiments have validated the effectiveness of the proposed method.

Chromium (Cr) is an important material, but also one of the most toxic heavy metal pollutants, showing great threat to human health and ecological environment, thus, accurate and rapid detection of Cr 3+ has far-reaching significance. In this work, based on the ligand of 2,3,4,5,6-pentafluorobenzoic acid (HPFBA) that does not contains oscillation effect group such as "CH, OH, and NH bond", three rare earth dinuclear cluster of Ln 2 (PFBA) 6 (phen) 2 (H 2 O) 2 (Ln = Tb 3+ 1-Tb, Eu 3+ 1-Eu, Gd 3+ 1-Gd, phen = 1,10-phenanthroline) were obtained. 1-Tb shows excellent stability and luminescence properties. In depth investigation reveals that 1-Tb shows quick detection towards Cr 3+ in water through luminescence "turn-off", with extremely short response time of 1.0 min, very low limit of detection (LOD) of 5.2 ppb and no interference from other ions. The LOD value is much lower than the total content of chromium for water in China (15 ppm, GB9078-1996). In the actual environment such as tap water, lake water, human, and serum, 1-Tb shows excellent detection and recovery rate for Cr 3+ . More interestingly, a fiber based paper of test paper that based on 1-Tb and ordinary filter paper was fabricated, which can probe Cr 3+ by visible color changes to the naked eye under UV light., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Toxoplasma gondii is an obligate protozoon that can infect all warm-blooded animals including humans. T. gondii afflicts one-third of the human population and is a detriment to the health of livestock and wildlife. Thus far, traditional drugs such as pyrimethamine and sulfadiazine used to treat T. gondii infection are inadequate as therapeutics due to relapse, long treatment period, and low efficacy in parasite clearance. Novel, efficacious drugs have not been available. Lumefantrine, as an antimalarial, is effective in killing T. gondii but has no known mechanism of action. We combined metabolomics with transcriptomics to investigate how lumefantrine inhibits T. gondii growth. We identified significant alternations in transcripts and metabolites and their associated functional pathways that are attributed to lumefantrine treatment. RH tachyzoites were used to infect Vero cells for three hours and subsequently treated with 900 ng/mL lumefantrine. Twenty-four hours post-drug treatment, we observed significant changes in transcripts associated with five DNA replication and repair pathways. Metabolomic data acquired through liquid chromatography-tandem mass spectrometry (LC-MS) showed that lumefantrine mainly affected sugar and amino acid metabolism, especially galactose and arginine. To investigate whether lumefantrine damages T. gondii DNA, we conducted a terminal transferase assay (TUNEL). TUNEL results showed that lumefantrine significantly induced apoptosis in a dose-dependent manner. Taken together, lumefantrine effectively inhibited T. gondii growth by damaging DNA, interfering with DNA replication and repair, and altering energy and amino acid metabolisms.

Trichinellosis is caused by Trichinella spiralis, a meat-borne zoonotic disease transmitted to humans through the consumption of infected undercooked or raw meat. Surveillance using safe and precise diagnostic tools to diagnose T. spiralis in sheep is needed to assess the incidence and probability of transmission from sheep to humans. In this study, we developed a real-time PCR assay to detect T. spiralis DNA in ovine muscle samples that can be used as an alternative surveillance tool to ensure food safety using newly designed primers. The assay is specific for the Scfld4 gene of Trichinella (T1) and enables the detection of larvae in ovine muscle tissue samples with high sensitivity and specificity. Trichuris ovis, Oesophagostomum dentatum, Haemonchus contortus, and Bunostomum trigonocephalum showed no nonspecific amplification. The assay could detect Trichinella DNA concentrations as low as 0.0026 ng/μL, equivalent to 0.0064 larvae, indicating a high sensitivity for T. spiralis detection. We used this real-time PCR to detect 73 ovine muscle samples from an ovine abattoir, and five samples tested positive via real-time PCR but negative via microscopy. This assay may provide a more specific and sensitive method for rapidly detecting Trichinella larvae in ovine muscle tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

There are significant differences in energy footprints among individual households. This study uses an environmentally extended input-output approach to estimate the per capita household energy footprint (PCHEF) of 10 different income groups in China's 30 provinces and analyzes the heterogeneity of household consumption categories, and finally measures the energy equality of households in each province by measuring the energy footprint Gini coefficient (EF-Gini). It is found that the energy footprint of the top 10% income households accounted for about 22% of the national energy footprint in 2017, while the energy footprint of the bottom 40% income households accounted for only 24%. With the growth of China's economy, energy footprint inequality has declined spatially and temporally. Firstly, wealthier coastal regions have experienced greater convergence in their energy footprint than poorer inland regions. Secondly, China's household EF-Gini has declined from 0.38 in 2012 to 0.36 in 2017. This study shows that China's economic growth has not only raised household income levels, but also reduced energy footprint inequality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cu-based catalysts have been widely applied in electroreduction of carbon dioxide (CO 2 ER) to produce multicarbon (C 2+ ) feedstocks (e.g., C 2 H 4 ). However, the high energy barriers for CO 2 activation on the Cu surface is a challenge for a high catalytic efficiency and product selectivity. Herein, we developed an in situ *CO generation and spillover strategy by engineering single Ni atoms on a pyridinic N-enriched carbon support with a sodalite (SOD) topology (Ni-SOD/NC) that acted as a donor to feed adjacent Cu nanoparticles (NPs) with *CO intermediate. As a result, a high C 2 H 4 selectivity of 62.5 % and an industrial-level current density of 160 mA cm -2 at a low potential of -0.72 V were achieved. Our studies revealed that the isolated NiN 3 active sites with adjacent pyridinic N species facilitated the *CO desorption and the massive *CO intermediate released from Ni-SOD/NC then overflowed to Cu NPs surface to enrich the *CO coverage for improving the selectivity of CO 2 ER to C 2 H 4 ., (© 2023 Wiley-VCH GmbH.)

Background: In recent years, liquid biopsy has shown great potential for improving cancer diagnosis and treatment. This study aimed to explore the trends and prospects in liquid biopsy for cancer from a bibliometric perspective., Methods: Reviews and articles on liquid biopsy and cancer were collected from the Web of Science Core Collection (WoSCC). Key bibliometric characteristics were analyzed using CiteSpace. Co-occurrence analysis of keywords and co-citation analysis of references was performed., Results: A total of 6331 publications from 11 years of scientific research were retrieved. Ninety-five countries and 7004 institutions in liquid biopsy and cancer contributed. The United States (US) and China published the most articles. The institution with the most published articles was the University of Texas MD Anderson Cancer Center. The most published journals were Cancer and Frontiers in Oncology. "Bettegowda (2014)" was the most cited reference with the highest burst strength in the last decade. Cluster analysis revealed that the recent hot topics were "circulating tumor cells," "cancer," and "exosomes.", Conclusions: This bibliometric analysis maps the basic knowledge structure of the field of liquid biopsy for cancer. The field is entering a phase of rapid development. The hot spots identified in this study deserve further investigation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Non-Hermitian metasurfaces provide an excellent platform for the study of parity-time (PT) symmetry transition. The exceptional point (EP) in the transition process exhibits peculiar physical phenomena and enriches the development of metasurfaces. In this study, a terahertz metal-graphene hybrid metasurface that can study PT symmetry transition and EP in transmission and reflection polarization channels is designed by using the phase transition characteristics of VO 2 . The tunable asymmetric loss and PT symmetry transition can be actively controlled by changing the Fermi energy of the graphene strip. Interestingly, owing to the special chirality of the structure, the original metasurface, and the mirrored metasurface degenerate into a circularly polarized state with opposite rotations at the same Fermi energy. The π-phase mutation at EP is observed following the interaction of circularly polarized waves and the metasurface and is expected to have good application prospects in environmental monitoring and gas sensing.

Background: The COVID-19 pandemic has spread rapidly and heavily hit the globe, and the mutation and transmission speed of the coronavirus have accelerated so that the world is still in danger. Thus, this study aims to investigate the participants' risk perception and explore the associations of risk perception of COVID-19 with negative emotions, information value perception and other related dimensions., Methods: A cross-sectional, population-based online survey was conducted from April 4 to 15, 2020, in China. A total of 3,552 participants were included in this study. A descriptive measure of demographic information was used in this study. Multiple regression models and moderating effect analysis were used to estimate the effect of potential associations of risk perceptions., Results: Those who showed negative emotions (depressed, helplessness, loneliness) and perceived video information in social media to be useful were positively correlated with risk perception, whereas individuals who perceived experts' advice to be useful, shared risk information with friends and thought that their community made adequate emergency preparation reported lower risk perception. The moderating effect of information perceived value (β = 0.020, p < 0.001) on the relationship between negative emotion and perception of risk was significant., Conclusions: Individual differences in risk cognition during the COVID-19 pandemic were observed in subgroups of age level. Furthermore, the role of negative emotional states, the perceived usefulness of risk information and the sense of security also contributed to improving the public's risk perception. It is crucial for authorities to focus on residents' negative emotions and to clarify misinformation in accessible and effective ways in a timely manner., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Sang, Wu, Feng, Long, Ye, Yan, Sun, Ji and Tang.)

FeOOH nanorods, as one-dimensional nanomaterials, have been widely used in many fields due to their stable properties, low cost, and easy synthesis, but their application in the field of chemiluminescence (CL) is rarely reported. In this work, FeOOH nanorods were synthesized by a simple and environmentally friendly one-pot hydrothermal method and used for the first time as a catalyst for generating strong CL with luminol without additional oxidant. Remarkably, luminol-FeOOH exhibits about 250 times stronger CL than the luminol-H 2 O 2 system. Its CL intensity was significantly quenched by uric acid. We established a simple, rapid, sensitive, and selective CL method for the detection of uric acid with a linear range of 20-1000 nM and a detection limit of 6.3 nM (S/N = 3). In addition, we successfully applied this method to the detection of uric acid in human serum, and the standard recoveries were 95.6-106.4%.

Weak interlayer van der Waals (vdW) bonding has significant impact on the surface/interface structure, electronic properties, and transport properties of vdW layered materials. Unraveling the complex atomistic dynamics and structural evolution at vdW surfaces is therefore critical for the design and synthesis of the next-generation vdW layered materials. Here, we show that Ge/Bi cation diffusion along the vdW gap in layered GeBi 2 Te 4 (GBT) can be directly observed using in situ heating scanning transmission electron microscopy (STEM). The cation concentration variation during diffusion was correlated with the local Te 6 octahedron distortion based on a quantitative analysis of the atomic column intensity and position in time-elapsed STEM images. The in-plane cation diffusion leads to out-of-plane surface etching through complex structural evolutions involving the formation and propagation of a non-centrosymmetric GeTe 2 triple layer surface reconstruction on fresh vdW surfaces, and GBT subsurface reconstruction from a septuple layer to a quintuple layer. Our results provide atomistic insight into the cation diffusion and surface reconstruction in vdW layered materials., (© 2023. The Author(s).)

Diagnostic results can be radically influenced by the quality of 2D ovarian-tumor ultrasound images. However, clinically processed 2D ovarian-tumor ultrasound images contain many artificially recognized symbols, such as fingers, crosses, dashed lines, and letters which assist artificial intelligence (AI) in image recognition. These symbols are widely distributed within the lesion's boundary, which can also affect the useful feature-extraction-utilizing networks and thus decrease the accuracy of lesion classification and segmentation. Image inpainting techniques are used for noise and object elimination from images. To solve this problem, we observed the MMOTU dataset and built a 2D ovarian-tumor ultrasound image inpainting dataset by finely annotating the various symbols in the images. A novel framework called mask-guided generative adversarial network (MGGAN) is presented in this paper for 2D ovarian-tumor ultrasound images to remove various symbols from the images. The MGGAN performs to a high standard in corrupted regions by using an attention mechanism in the generator to pay more attention to valid information and ignore symbol information, making lesion boundaries more realistic. Moreover, fast Fourier convolutions (FFCs) and residual networks are used to increase the global field of perception; thus, our model can be applied to high-resolution ultrasound images. The greatest benefit of this algorithm is that it achieves pixel-level inpainting of distorted regions without clean images. Compared with other models, our model achieveed better results with only one stage in terms of objective and subjective evaluations. Our model obtained the best results for 256 × 256 and 512 × 512 resolutions. At a resolution of 256 × 256, our model achieved 0.9246 for SSIM, 22.66 for FID, and 0.07806 for LPIPS. At a resolution of 512 × 512, our model achieved 0.9208 for SSIM, 25.52 for FID, and 0.08300 for LPIPS. Our method can considerably improve the accuracy of computerized ovarian tumor diagnosis. The segmentation accuracy was improved from 71.51% to 76.06% for the Unet model and from 61.13% to 66.65% for the PSPnet model in clean images.

This paper examines the impact of agricultural mechanization services (AMS) on rural household income and income gap, utilizing the recentered influence function regression method and publicly available data collected through the China Labor-force Dynamics Survey. The results of this study shed light on various impacts of AMS. First, agricultural mechanization services can significantly increase rural household income, but there is heterogeneity in the impact on rural household income in different quantiles. The effect of income growth on medium-income and low-income groups is greater. Second, agricultural mechanization services help to narrow the income gap between rural households and alleviate income inequality in rural areas. Third, the effect of agricultural mechanization services on reducing the income gap between rural households in the eastern and western regions is significantly stronger than that in the central region. Finally, further analysis based on income source structure reveals that agricultural mechanization services can significantly reduce the non-agricultural income gap of rural households, but the impact on the agricultural income gap is negligible. Our findings highlight the importance of government's efforts in promoting the development of agricultural mechanization service market in order to improve the income inequality in rural areas., (© 2023 The Authors.)

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence. Furthermore, ESC-EVs have achieved preliminary efficacy while treating many age-related diseases. The present study aimed to test the effect of ESC-EVs on the replicative senescence model of RPE cells as well as its mechanism. The results showed that ESC-EVs enhanced the proliferative ability and cell cycle transition of senescent RPE cells, whereas reduced the senescence-associated galactosidase (SA-β-gal) staining rate, as well as the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Moreover, classical markers of cellular senescence p21 WAF1/CIP1 (p21) and p16 INK4a (p16) were downregulated. The bioinformatic analysis and further study showed that the inhibition of the p38MAPK pathway by ESC-EVs played a pivotal role in RPE cellular senescence-reversing effect, which was ameliorated or even abolished when dehydrocorydaline were administrated simultaneously, demonstrating that ESC-EVs can effectively reverse RPE cellular senesence by inhibiting the p38MAPK pathway, thus highlights the potential of ESC-derived EVs as biomaterials for preventative and protective therapy in AMD., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM)., Aim of the Study: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model., Materials and Methods: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay., Results: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF)., Conclusion: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier B.V.)

Diamond holds promise for optoelectronic devices working in high-frequency, high-power and high-temperature environments, for example in some aspect of nuclear energetics industry processing and aerospace due to its wide bandgap (5.5 eV), ultimate thermal conductivity, high-pressure resistance, high radio frequency and high chemical stability. In the last several years, p-type B-doped diamond (BDD) has been fabricated to heterojunctions with all kinds of non-metal oxide (AlN, GaN, Si and carbon-based semiconductors) to form heterojunctions, which may be widely utilized in various optoelectronic device technology. This article discusses the application of diamond-based heterostructures and mainly writes about optoelectronic device fabrication, optoelectronic performance research, LEDs, photodetectors, and high-electron mobility transistor (HEMT) device applications based on diamond non-metal oxide (AlN, GaN, Si and carbon-based semiconductor) heterojunction. The discussion in this paper will provide a new scheme for the improvement of high-temperature diamond-based optoelectronics.

The rapid emergence of SARS-CoV-2 variants of concern, the complexity of infection, and the functional redundancy of host factors, underscore an urgent need for broad-spectrum antivirals against the continuous COVID-19 pandemic, with drug repurposing as a viable therapeutic strategy. Here we report the potential of RNA G-quadruplex (RG4)-targeting therapeutic strategy for SARS-CoV-2 entry. Combining bioinformatics, biochemical and biophysical approaches, we characterize the existence of RG4s in several SARS-CoV-2 host factors. In silico screening followed by experimental validation identify Topotecan (TPT) and Berbamine (BBM), two clinical approved drugs, as RG4-stabilizing agents with repurposing potential for COVID-19. Both TPT and BBM can reduce the protein level of RG4-containing host factors, including ACE2, AXL, FURIN, and TMPRSS2. Intriguingly, TPT and BBM block SARS-CoV-2 pseudovirus entry into target cells in vitro and murine tissues in vivo. These findings emphasize the significance of RG4 in SARS-CoV-2 pathogenesis and provide a potential broad-spectrum antiviral strategy for COVID-19 prevention and treatment., Competing Interests: The authors declare no competing interest., (Copyright: © 2023 Tong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Immune checkpoint inhibitors (ICIs) like programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown considerable efficacy in several important cancers including primary liver cancer (PLC) like hepatocellular carcinoma and cholangiocarcinoma. However, only some patients with PLC will benefit, so combination therapy and biomarker classification detected by next-generation sequencing or immunohistochemistry are very important. Herein, we briefly summarize ICI-based therapies and stratify these evolving therapies for advanced PLC into three stages of immunotherapies Mark (Mk.) 1.0, 2.0, and 3.0. We illustrated the significance of ICI monotherapy (Mk. 1.0), offering combinational approaches with traditional strategies (Mk. 2.0) and additional locoregional therapy (Mk. 3.0) to achieve longer survival and even meet the "No Evidence of Disease" status. We also highlight the importance of biomarkers and prognostic factors for patients with advanced PLC treated with ICI-based therapies. Multidisciplinary team management should be investigated and collaborated closely to manage adverse events and sequential therapy suggestions for patients., Competing Interests: Competing interests: Not applicable., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Strabismus and amblyopia are common ophthalmologic developmental diseases caused by abnormal visual experiences. However, the underlying pathogenesis and visual defects are still not fully understood. Most studies have used experimental interference to establish disease-associated animal models, while ignoring the natural pathophysiological mechanisms. This study was designed to investigate whether natural strabismus and amblyopia are associated with abnormal neurological defects. We screened one natural strabismic monkey ( Macaca fascicularis ) and one natural amblyopic monkey from hundreds of monkeys, and retrospectively analyzed one human strabismus case. Neuroimaging, behavioral, neurophysiological, neurostructural, and genovariation features were systematically evaluated using magnetic resonance imaging (MRI), behavioral tasks, flash visual evoked potentials (FVEP), electroretinogram (ERG), optical coherence tomography (OCT), and whole-genome sequencing (WGS), respectively. Results showed that the strabismic patient and natural strabismic and amblyopic monkeys exhibited similar abnormal asymmetries in brain structure, i.e., ipsilateral impaired right hemisphere. Visual behavior, visual function, retinal structure, and fundus of the monkeys were impaired. Aberrant asymmetry in binocular visual function and structure between the strabismic and amblyopic monkeys was closely related, with greater impairment of the left visual pathway. Several similar known mutant genes for strabismus and amblyopia were also identified. In conclusion, natural strabismus and amblyopia are accompanied by abnormal asymmetries of the visual system, especially visual neurophysiological and neurostructural defects. Our results suggest that future therapeutic and mechanistic studies should consider defects and asymmetries throughout the entire visual system.

Background: Lenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study., Methods: Patients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated., Results: Fifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6-19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0-NA), and 9.27 (95% CI: 7.1-11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%-56.7%), 91.2% (95% CI: 81.1%-96.2%), and 73.7% (95% CI: 61.0%-83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P<0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported., Conclusion: Lenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Xue, Wang, Wang, Zhang, Wang, Zhang, Yang, Long, Yang, Sang and Zhao.)

Real-time dense view synthesis based on three-dimensional (3D) reconstruction of real scenes is still a challenge for 3D light-field display. It's time-consuming to reconstruct an entire model, and then the target views are synthesized afterward based on volume rendering. To address this issue, Light-field Visual Hull (LVH) is presented with free-viewpoint texture mapping for 3D light-field display, which can directly produce synthetic images with the 3D reconstruction of real scenes in real-time based on forty free-viewpoint RGB cameras. An end-to-end subpixel calculation procedure of the synthetic image is demonstrated, which defines a rendering ray for each subpixel based on light-field image coding. In the ray propagation process, only the essential spatial point of the target model is located for the corresponding subpixel by projecting the frontmost point of the ray to all the free-viewpoints, and the color of each subpixel is identified in one pass. A dynamic free-viewpoint texture mapping method is proposed to solve the correct graphic texture considering the free-viewpoint cameras. To improve the efficiency, only the visible 3D position and texture that contributes to the synthetic image are calculated based on backward ray tracing rather than computing the entire 3D model and generating all elemental images. In addition, an incremental calibration method by dividing camera groups is proposed to satisfy the accuracy. Experimental results show the validity of our method. All the rendered views are analyzed for justifying the texture mapping method, and the PSNR is improved by an average of 11.88dB. Finally, LVH can achieve a natural and smooth viewing effect at 4K resolution and the frame rate of 25 ∼ 30fps with a large viewing angle.

Dihydroartemisinin (DHA), a potent antimalarial drug, also exhibits distinct property in modulation on T reg and B cells, which has been recognized for decades, but the underlying mechanisms remain understood. Herein we revealed that DHA could promote T reg proliferation, meanwhile, suppress B cell expansion in germinal centers, and consequently decrease the number of circulating plasma cells and the content of serum immunoglobulins. Further, DHA-activated T reg significantly mitigated lipopolysaccharide-induced and malaria-associated inflammation. All these scenarios were attributed to the upregulation of c-Fos expression by DHA and enhancement of its interaction with target genes in both T reg and circulating plasma cells with bilateral cell fates. In T reg , the c-Fos-DHA complex upregulated cell proliferation-associated genes and promoted cell expansion; whereas in plasma cells, it upregulated the apoptosis-related genes resulting in decreased circulating plasma cells. Thus, the bilateral immunoregulatory mechanism of DHA was elucidated and its application in the treatment of autoimmune diseases is further justified., (© 2023. The Author(s).)

Limited by the low space-bandwidth product of the spatial light modulator (SLM), it is difficult to realize multiview holographic three-dimensional (3D) display. To conquer the problem, a method based on the holographic optical element (HOE), which is regarded as a controlled light element, is proposed in the study. The SLM is employed to upload the synthetic phase-only hologram generated by the angular spectrum diffraction theory. Digital grating is introduced in the generation process of the hologram to achieve the splicing of the reconstructions and adjust the position of the reconstructions. The HOE fabricated by the computer-generated hologram printing can redirect the reconstructed images of multiview into multiple viewing zones. Thus, the modulation function of the HOE should be well-designed to avoid crosstalk between perspectives. The experimental results show that the proposed system can achieve multiview holographic augmented reality (AR) 3D display without crosstalk. The resolution of each perspective is 4K, which is higher than that of the existing multiview 3D display system.

Background: Cell cycle-related genes ( CDK1 , CDK5 , CDC20 , CCNA2 , CCNB1 , and CCNB2 ) play important roles in the regulation of mitotic cell cycle in eukaryotes. However, the correlation between cell cycle-related genes and tumor-infiltrating and prognosis of hepatocellular carcinoma (HCC) needs further investigation. Methods: Two public websites, Tumor Immune Estimate Resource (TIMER) and Oncomine, were used to assess the expression levels of cycle-related genes. We also analyzed the protein expression levels of six cell cycle-related genes using the HPA database. In addition, Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) database were used to investigate the impact of cell cycle-related gene expression levels on the clinical prognosis of HCC. The correlation between cell cycle-related genes and cancer immune infiltrates was analyzed through TIMER site. Subsequently, GEPIA and TIMER database were used to assess the correlation between the expression of six cell cycle-related genes and polygenic markers in monocytes and macrophages, respectively. The cell cycle-related genes were also analyzed to find the associated genes with the highest alteration frequency, by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) approaches of Metascape and String database, respectively. Results: The expression levels of cell cycle-related genes were up-regulated in tumor tissues compared with normal tissues. Subsequently, the expression of high cell cycle-related genes was positively correlated with poor overall survival (OS) and progression-free survival (PFS) in HCC, for CDK1 (OS: HR = 2.15, P = 1.1E-05 PFS: HR = 2.03, P = 2.3E-06), CDK5 (OS: HR = 1.85, P = 0.0035 PFS: HR = 1.26, P = 0.17), CDC20 (OS: HR = 2.49, P = 5.1E-07 PFS: HR = 1.77, P = 0.00012), CCNA2 (OS: HR = 1.92, P = 0.00018 PFS: HR = 1.96, P = 5.2E-06), CCNB1 (OS: HR = 2.34, P = 3.4E-05 PFS: HR = 1.97, P = 5.3E-06), and CCNB2 (OS: HR = 1.91, P = 0.0013 PFS: HR = 1.63, P = 0.0011), respectively. Furthermore, the transcription level of cell cycle-related genes was significantly correlated with immune infiltrating levels of CD4+ T and CD8+ T cells, neutrophils, macrophages, and dendritic cells (DCs) in HCC, respectively. Amongst them, the expression levels of CDK1 , CDC20 , CCNA2 , CCNB1 and CCNB2 manifest strongly correlated with diverse immune marker sets in HCC. Conclusions: Our results demonstrated that cell cycle-related genes played key roles in the prognosis of HCC. Meanwhile, they were significantly correlated with immune infiltrating levels of CD4 + T cells, CD8 + T cells, neutrophils, macrophages and DCs in HCC, respectively. In addition, CDK1 , CDC20 , CCNA2 , CCNB1 and CCNB2 expressions may be involved in the regulation of monocytes and tumor-associated macrophages (TAMs) in HCC, respectively. These findings strongly suggested that cell cycle-related genes could be used as novel biomarkers for exploring the prognosis and immune cells infiltration of HCC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients.

Background: This study aimed to describe the relationship between the different levels of intraoperative mean arterial blood pressure (MAP) and postoperative delirium in elderly patients undergoing gastrointestinal laparoscopic surgery., Materials and Methods: This prospective controlled clinical trial enrolled 116 patients aged 65 to 85 years who underwent gastrointestinal laparoscopic surgery. These patients were randomized 1:1 to a MAP goal of 65 to 85 mmHg (L group) or an 86 to 100 mmHg (H group). The primary endpoint was the incidence of postoperative delirium, assessed twice daily with the Confusion Assessment Method (CAM) and Richmond Agitation-Sedation Scale (RASS) during the first five postoperative days. Delirium severity was evaluated with the Delirium-O-Meter (D-O-M)., Results: 108 patients (L group n = 55, H group n = 53) were eventually included in intention-to-treat analyses. Postoperative delirium occurred in 18 (32.7%) of 55 cases of L group and in 15 (28.3%) of 53 cases of H group. The incidence of delirium subtypes between the two groups: hypoactive delirium 14.5% (8/55) vs 11.3% (6/53); hyperactive delirium 7.3% (4/55) vs 3.8% (2/53); mixed delirium 10.9% (6/55) vs 13.2% (7/53). However, the L group showed higher D-O-M scores of the first episode of delirium: 14.5 (Q1 = 12, Q3 = 18.5) vs 12 (Q1 = 10, Q3 = 14), which means the delirium is more severe., Conclusions: Compared with 65 to 85 mmHg, maintaining intraoperative MAP at 86-100 mmHg did not reduce the incidence of postoperative delirium in elderly patients undergoing gastrointestinal laparoscopic surgery. However, the severity of delirium could be reduced and blood loss is a risk factor for postoperative delirium., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aiming to the personalized laser therapy of nevus of Ota (NO), a local thermal non-equilibrium model was employed to optimize laser wavelength, pulse duration, and energy density under different melanin depth and volume fraction. According to our simulation, the optimal pulse duration is between 15 and 150 ns to limit heat transfer inside the hyperplastic melanin, and 50 ns is recommended to decrease the energy absorption by normal melanin in epidermis. Correlations of the minimum and the maximum energy densities are proposed with respect to melanin depth and volume fraction for the 755-nm and 1064-nm lasers. For the same NO type, the therapy window of the 755-nm laser is larger than that of 1064-nm. For NO with shallow depth or low volume fraction, the 755-nm laser is recommended to make the treatment more stable owing to its lager therapy window. For deeper depth or higher volume fraction, the 1064-nm laser is recommended to avoid thermal damage of epidermis. Through comparison with clinical data, the optimized laser parameters are proved practicable since high cure rate can be achieved when energy density falls into the range of predicted therapy window. With developing of non-invasive measurement technology of melanin content and distribution, personalized treatment of NO maybe possible in the near future., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The soybean aphid Aphis glycines Matsumura is a predominant insect pest in Asia and North America and causes great losses to soybean. The release of genome data for A. glycines will facilitate gene function research in the future. However, suitable reference genes for A. glycines under various experimental conditions are scarce. To search for appropriate reference genes for A. glycines, nine candidate reference genes, including Act, α-Tub, β-Tub, RPS12, RPS18, RPL5, RPL27, EF1α, and Fer, were tested under six experimental conditions to evaluate their suitability for use in the normalization of qRT‒PCR data. Results showed that EF1α and RPS12 were optimal for the developmental stages of A. glycines, RPS18 and RPS12 were appropriate for wing dimorphism, β-Tub and RPS18 were suitable for different tissues and RPL5, and α-Tub could be used for normalization at different temperatures. β-Tub and EF1α could be proposed as reference genes for insecticide treatment, and RPL5 and RPS12 were found to be the most stable reference genes in different photoperiods. The results provide appropriate reference genes for analyzing gene expression in A. glycines and contribute to future research on the molecular physiology and biochemistry of A. glycines., (© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lenvatinib is a standard first-line systemic therapy in advanced hepatocellular carcinoma (aHCC) and is widely used in all lines. However, the efficacy and safety of immune checkpoint inhibitors (ICIs) plus molecular targeted agents (MTAs) after the progression of lenvatinib treatment are unclear., Objective: The aim of this study was to evaluate the anticancer effects of ICI plus MTA in patients with aHCC who progressed after lenvatinib., Methods: We retrospectively included aHCC patients treated with ICI plus MTA after the progression of lenvatinib from two medical centers. Participants who continued lenvatinib treatment were classified into the "ICI+Lenva" group, while the "ICI+Others" group included patients receiving other MTAs. The efficacy endpoints were progression-free survival (PFS), post-progression survival (PPS), overall survival (OS), and tumor response following RECIST v1.1. Safety was evaluated according to Common Terminology Criteria for Adverse Events v5.0., Results: In this study, 85 eligible aHCC patients were enrolled, including 58 in the ICI+Lenva group and 27 in the ICI+Others group. At a median follow-up time of 22.8 months, the median PPS and PFS were 14.0 (95% CI: 9.0-18.2) and 4.5 months (95% CI: 3.5-8.3), respectively. The objective response and disease control rates were 10.6% and 52.9%, respectively. No significant differences were observed in any of the efficacy endpoints between the two groups. Prolonged PPS was associated with Child-Pugh grade A, AFP < 400 IU/ml, and concomitant locoregional treatment. All patients experienced adverse events (AEs), but no fatal AEs were observed., Conclusion: ICI plus MTA in aHCC patients after the progression of lenvatinib presented high antitumor activity and safety. Patients could continue lenvatinib treatment and receive ICIs as well as locoregional treatment to achieve better OS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Chen, Yang, Wang, Zhang, Wang, Wang, Zhang, Xue, Long, Li, Sun, Xun, Liu, Chen, Song, Yang, Lu, Mao, Sang, Lu and Zhao.)

Trypanosoma brucei , the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca 2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xie, Liang, Jiang, Liu, Zhang, Li, Zhang, Sang, Feng, Chen, Zhang and Chen.)

Background: The prognosis of biliary neuroendocrine neoplasms (NENs) patients is affected by the status of metastatic lymph nodes. The purpose of this study was to explore the prognostic value of the log odds of positive lymph nodes (LODDS) and develop a novel nomogram to predict the overall survival (OS) in biliary NENs patients., Methods: A total of 125 patients with histologically confirmed biliary NENs were selected from the Surveillance, Epidemiology and End Results (SEER) database and further divided into training and validation cohorts. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits and clinical utility of the nomogram were quantified and compared with those of the SEER staging system using decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). The risk stratifications of the nomogram and the SEER staging system were compared., Results: LODDS showed the highest accuracy in predicting OS for biliary NENs. The C-index (0.789 for the training cohort and 0.890 for the validation cohort) and the time-dependent AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. The calibration plots showed a high degree of consistency. The DCA, NRI, and IDI indicated that the nomogram performed significantly better than the SEER staging system., Conclusion: A novel LODDS-incorporated nomogram was developed and validated to assist clinicians in evaluating the prognosis of biliary NENs patients., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Background and Objective: Owing to the greater absorption affinity for lipo-rich tissue than water, the 1210 nm laser is a promising candidate for transcutaneous lipolysis in the near-infrared band. However, fat reduction is limited because laser therapy may yield thermal injury of normal tissue. A new protocol to incorporate multipulsed cryogen spray cooling is beneficial to improve the lipolysis effect, and the parameters of laser and cooling can be optimized via skin histopathological analysis., Materials and Methods: A murine in vivo model of inguinal tissue of SD rats was established to test the effectivity of transcutaneous lipolysis protocol by R134a multipulsed spray cooling assisted 1210 nm laser irradiation. Tissue response of lipolysis with/without cooling 10 days post the treatment was evaluated by histopathological analysis of skin samples stained with hematoxylin-eosin (HE), through which safe and effective parameters for lipolysis were determined., Results: From histopathological analysis of the inguinal tissue of SD rats irradiated by the 1210 nm laser alone, the optimal durations are respectively 7 and 3 s (seconds) for low-dosage (6 W) and high-dosage (9 W) therapy, with pronounced lipolysis effect and minimum injury of skin tissue. The multipulsed spray cooling by R134a with a pulse duration of 10 ms (milliseconds), a pulse delay of 2000 ms, and a pulse number of 5 can be introduced to assist the 1210 nm laser therapy with a power of 9 W and a duration of 7 s to achieve desirable fat liquefaction while keeping the complete structure of skin tissue as well as esthetic-related beneficial effects of hair removal and skin rejuvenation., Conclusion: Excellent lipolysis effect can be achieved via R134a multipulsed spray cooling assisted high-dosage 1210 nm laser irradiation with reasonably matched laser and cooling parameters. The protocol is as follows: Start MP-CSC for one cycle, and then fire the laser with specific power and duration, while keeping MP-CSC accordingly. This new protocol may promote the safe and effective clinical implement of transcutaneous laser lipolysis in body contouring., (© 2022 Wiley Periodicals LLC.)

Glabridin is a prenylated isoflavonoid with considerable anticancer property. Reactive oxygen species (ROS) have evolved as regulators of many cellular signaling pathways in prostate cancer (PC). However, the role of ROS signaling in the anticancer activity of glabridin has not been investigated. Here, we attempted to evaluate the effect of glabridin on PC and the involvement of ROS signaling. Intracellular ROS and mitochondrial ROS (mitoROS) production in PC cell lines, DU-145 and LNCaP, were measured by H2DCFDA and MitoSOX Red staining, respectively. MTT assay was used to analyze the cellular viability. EdU staining assay was conducted to analyze the cell proliferation. To analyze apoptotic rate, TUNEL assay was performed. Caspase-3 activity was detected to reflect cell apoptosis. Western blot was carried out to detect the expression levels of Akt and p-Akt. We found that intracellular ROS and mitoROS levels were dose-dependently upregulated after glabridin treatment in both DU-145 and LNCaP cells, which was reversed by the treatment of ROS inhibitor, N-acetyl-L-cysteine (NAC). Glabridin inhibited the cell viability and reduced the number of EdU-positive DU-145 and LNCaP cells, which were respectively proved by MTT assay and EdU staining assay. Glabridin promoted cell death with increased apoptotic rate and caspase-3 activity in DU-145 and LNCaP cells. The effects of glabridin on cell proliferation and apoptosis were reversed by NAC. Moreover, glabridin suppressed the ratio of p-Akt/Akt, while NAC mitigated the decreased p-Akt/Akt ratio. In addition, the effects of glabridin on cell proliferation and apoptosis were also attenuated by Akt activator, SC79. Collectively, our results demonstrated that glabridin suppressed proliferation and induced apoptosis in PC cells via regulating ROS-mediated PI3K/Akt pathway. These findings suggested that glabridin might hold a promising prospective as a therapeutic agent against PC., (© 2022 Wiley Periodicals LLC.)

Due to the limited pixel pitch of the spatial light modulator (SLM), the field of view (FOV) is insufficient to meet binocular observation needs. Here, an optimized controlling light method of a binocular holographic three-dimensional (3D) display system based on the holographic optical element (HOE) is proposed. The synthetic phase-only hologram uploaded onto the SLM is generated with the layer-based angular spectrum diffraction theory, and two different reference waves are introduced to separate the left view and the right view of the 3D scene. The HOE with directional controlling light parameters is employed to guide binocular information into the left-eye and the right-eye viewing zones simultaneously. Optical experiments verify that the proposed system can achieve binocular holographic augmented reality 3D effect successfully with real physical depth, which can eliminate the accommodation-vergence conflict and visual fatigue problem. For each perspective, the FOV is 8.7° when the focal length of the HOE is 10 cm. The width of the viewing zone is 2.3 cm when the viewing distance is 25 cm.

Light field (LF) image super-resolution (SR) can improve the limited spatial resolution of LF images by using complementary information from different perspectives. However, current LF image SR methods only use the RGB data to implicitly exploit the information among different perspectives, without paying attention to the information loss from raw data to RGB data and the explicit structure information utilization. To address the first issue, a data generation pipeline is developed to collect LF raw data for LF image SR. In addition, to make full use of the multiview information, an end-to-end convolutional neural network architecture (namely, LF-RawSR) is proposed for LF image SR. Specifically, an aggregated module is first used to fuse the angular information based on a volume transformer with plane sweep volume. Then the aggregated feature is warped to all LF views using a cross-view transformer for nonlocal dependencies utilization. The experimental results demonstrate that our method outperforms existing state-of-the-art methods with a comparative computational cost, and fine details and clear structures can be restored.

A holographic function screen (HFS) can recompose the wavefront and re-modulate the light-field distribution from a three-dimensional (3D) light field display (LFD) system. However, the spread function of existing HFSs does not particularly suit integral imaging (II) 3D LFD systems, which causes crosstalk and reduces the sharpness of reconstructed 3D images. An optimized holographic function screen with a flat-top rectangular spread function (FRSF) was designed for an II 3D LFD system. A simulation was carried out through ray tracing, which verified that the proposed diffusion function could suppress crosstalk and improve the overall effect.

Introduction: Over recent years, 3D bioprinting has changed dramatically. The articles related to liver 3D bioprinting have not been quantitatively analyzed. In this article, we screen all articles related to liver 3D bioprinting until January 2022 and analyzed them using bibliometric citation analysis to characterize the current trends in liver 3D bioprinting. Methods: The articles were identified and analyzed from the Clarivate Analytics Web of Science Core Collection database. Results: Until 1 January 2022, 71 articles focusing on liver 3D bioprinting were identified. There was an increase in the number of articles in 2015. Most articles came from the USA ( n = 27), followed by South Korea ( n = 22), China ( n = 16), and Japan ( n = 5). The printing technology of liver 3D printing was the most studied topic ( n = 29). Biofabrication published the highest number of papers ( n = 16) with 1,524 total citations. Conclusion: Based on bibliometric analysis of the articles until January 2022, a comprehensive analysis of the liver 3D bioprinting articles highlighted the current trends and research topics of this field. The data should provide clinicians and researchers insight into future directions relative to the liver 3D bioprinting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jin, Liu, Du, Sang, Yang and Mao.)

Vaccination is one of the most vigorous ways to intervene in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Cases of autoimmune hepatitis (AIH) after coronavirus disease (COVID-19) vaccination have been increasingly reported. Twenty-seven cases of AIH are summarized in this study, providing emerging evidence of autoimmune reactions in response to various COVID-19 vaccines, including in patients with special disease backgrounds such as primary sclerosing cholangitis (PSC), liver transplantation, and previous hepatitis C virus (HCV) treatment. Molecular mimicry, adjuvants, epitope spreading, bystander activation, X chromosome, and sceptical hepatotropism of SARS-CoV-2 may account for, to some extent, such autoimmune phenomena. Immunosuppressive corticosteroids perform well with or without azathioprine in such post-COVID-19-vaccination AIH. However, determination of the exact mechanism and establishment of causality require further confirmation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zheng, Zhang, Xu, Lu and Sang.)

To date, hepatocytes derived from human-induced pluripotent stem cells (hiPSC) provide a potentially unlimited resource for clinical application and drug development. However, most hiPSC-derived hepatocyte-like cells initiated differentiation from highly purified definitive endoderm, which are insufficient to accurately replicate the complex regulation of signals among multiple cells and tissues during liver organogenesis, thereby displaying an immature phenotypic and short survival time in vitro . Here, we described a protocol to achieve codifferentiation of endoderm-derived hepatocytes and mesoderm-derived nonparenchymal cells by the inclusion of BMP4 into hepatic differentiation medium, which has a beneficial effect on the hepatocyte maturation and lifespan in vitro . Our codifferentiation system suggests the important role of nonparenchymal cells in liver organogenesis. Hopefully, these hepatocytes described here provide a promising approach in the therapy of liver diseases., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2022 Ying Shi et al.)

Prognosis prediction is difficult in hepatocellular carcinoma (HCC) due to high heterogeneity and complex etiology. It has recently been discovered that cuproptosis is a type of programmed cell death. However, its significance for HCC is still unclear. We analyzed mRNA expression profiles and clinical information from public databases to determine whether cuproptosis-related genes are associated with improved prognoses for HCC patients. The training cohort consisted of HCC patients from The Cancer Genome Atlas (TCGA), and the validation cohort relied on the International Cancer Genome Consortium (ICGC) database. We constructed a signature containing four genes using the least absolute shrinkage and selection operator (LASSO) COX regression model for calculating risk scores. Two risk groups were formed based on the median score. A significant improvement in survival was observed in the low-risk group compared to the high-risk. The multivariate Cox regression analysis showed that the risk score was an independent predictor of overall survival (OS). Further confirmation of the predictive accuracy of this signature is provided by receiver operating characteristic (ROC) analysis. Functional analysis revealed differences in immune status between the two risk groups. All the results described above were confirmed in the validation cohort. Therefore, a novel cuproptosis-related signature has the potential as a prognostic biomarker for HCC patients. Drugs developed to target cuproptosis-related genes may open up new pathways for treating HCC., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Three-dimensional (3D) light-field displays can provide an immersive visual experience, which has attracted significant attention. However, the generating of high-quality 3D light-field content in the real world is still a challenge because it is difficult to capture dense high-resolution viewpoints of the real world with the camera array. Novel view synthesis based on CNN can generate dense high-resolution viewpoints from sparse inputs but suffer from high-computational resource consumption, low rendering speed, and limited camera baseline. Here, a two-stage virtual view synthesis method based on cutoff-NeRF and 3D voxel rendering is presented, which can fast synthesize dense novel views with smooth parallax and 3D images with a resolution of 7680 × 4320 for the 3D light-field display. In the first stage, an image-based cutoff-NeRF is proposed to implicitly represent the distribution of scene content and improve the quality of the virtual view. In the second stage, a 3D voxel-based image rendering and coding algorithm is presented, which quantify the scene content distribution learned by cutoff-NeRF to render high-resolution virtual views fast and output high-resolution 3D images. Among them, a coarse-to-fine 3D voxel rendering method is proposed to improve the accuracy of voxel representation effectively. Furthermore, a 3D voxel-based off-axis pixel encoding method is proposed to speed up 3D image generation. Finally, a sparse views dataset is built by ourselves to analyze the effectiveness of the proposed method. Experimental results demonstrate the method's effectiveness, which can fast synthesize novel views and 3D images with high resolution in real 3D scenes and physical simulation environments. PSNR of the virtual view is about 29.75 dB, SSIM is about 0.88, and the synthetic 8K 3D image time is about 14.41s. We believe that our fast high-resolution virtual viewpoint synthesis method can effectively improve the application of 3D light field display.

Hypothesis: The use of water to reduce friction has always played a significant role in a wide range of areas ranging from biology to engineering. Many efforts have been made to extensively investigate the water behavior between two contacted surfaces, but its role in water-based friction remains incompletely understood., Experiments: Herein, we utilize the sum-frequency generation (SFG) spectroscopy to identify interfacial water structures upon adjusting the wettability of titanium dioxide (TiO 2 ) and silicon surfaces. And the corresponding wettability-tunable underwater friction is measured by atomic force microscopy (AFM)., Findings: It demonstrates that enhanced wettability induces higher friction on the TiO 2 surface but lower friction on the silicon surface. Although the tribological properties of TiO 2 show independence of surface forces in contrast to the case of silicon, both TiO 2 and silicon surfaces covered with homogeneous water molecules correspond to a lower friction coefficient. This observation indicates that a homogeneous interfacial water structure, dominating over surface forces, is of the utmost importance for achieving low friction. Our results shed new light on the origins of friction in the presence of water and reveal the ubiquitous role of interfacial water structures on friction., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)