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Background: Previously, research has reported associations of lipid and lipoprotein imbalances with carcinogenesis and cancer progression, so they have been considered as promising prognostic biomarkers for cancer in recent years. However, the correlation of preoperative serum triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) with non-small cell lung carcinoma (NSCLC) prognosis remains under exploration. Here, the study investigated the prognostic function of TG/HDL-C for NSCLC. Methods: The total combined group of this retrospective study enrolled 479 NSCLC patients from two tertiary referral hospitals, of which 223 patients were defined as the training group (Nanchang) and the remaining 256 were defined as the validation group (Wuhan). The cut-off of preoperative TG/HDL-C was determined through ROC curve in the training group and verified in the validation and combined groups subsequently. With one Cox proportional hazards model and K-M survival curves, a survival analysis was conducted. Results: In the training group, the optimal cut-off of TG/HDL-C was 1.02. Furthermore, the data based on the training group revealed a greater, shorter, overall survival (OS) in patients having a high TG/HDL-C (>1.02) than those having low TG/HDL-C (≤1.02). Meanwhile, in univariate and multivariate analysis, for prognostic OS among NSCLC patients, TG/HDL-C acted as one independent factor. All the results above were confirmed in the validation and combined groups. Conclusion: NSCLC patients with a comparatively low preoperative serum TG/HDL-C level had a correlation with well OS. TG/HDL-C possibly acted as one novel, effective prognostic biomarker for NSCLC patients.

To clarify the copyrights of 3D models of oblique photography (3DMOP) and guarantee their security, a novel security protection scheme of 3DMOP was proposed in this study by synergistically applying digital watermarking and data encryption. In the proposed scheme, point clouds were clustered first, and then the centroid and feature points of each cluster were calculated and extracted, respectively. Afterward, the watermarks were embedded into the point clouds cluster-by-cluster, taking distances between feature points and centroids as the embedding positions. In addition, the watermarks were also embedded using texture coordinates of 3DMOP to further enhance the robustness of the watermarking algorithm. Furthermore, Arnold transformation was performed on texture images of 3DMOP for security protection of classified or sensitive information. Experimental results have verified the strong imperceptibility and robustness of the proposed watermarking algorithm, as well as the high security of the designed data encryption algorithm. The outcomes of this work can refine the current security protection methods of 3DMOP and thus further expand their application scope.

A polymer-stabilized liquid crystal (PSLC) device has been a promising candidate in several scenarios like smart vehicle windows and glass curtain walls in recent years due to its remarkable features like a fast switch from the initial transparent state to the scattering state with a rather low driving voltage, high transmittance at off-state, and broad viewing angle. The electro-optical characteristics of PSLC devices are determined by the synergistic attributions of liquid crystal (LC) molecules and the influence of the polymer network exerted on the movement of LC molecules. A systematic study of the influence of the polymer network on the movement of LC molecules is conducted, with the polymer network formed by methoxy/cyano/carboxyl monomers and diacrylate C6M. The polymer network morphology of PSLC film is greatly affected by the molecular structures and content of monoacrylic monomers. Additionally, the electro-optical performance and peel strength of PSLC films could be improved by modulating the molecular structures and morphology of polymer networks. PSLC devices containing carboxyl monomers show enhanced electro-optical performance and peel strength due to their directional filiform topology. This study might provide guidance for optimizing the performance of PSLC devices and establishing the relationship between the molecular structure, polymer network morphology, and electro-optical performance of reverse-mode dimming films.

Polymer-dispersed liquid-crystal (PDLC) films have wide applications in light shutters, smart windows for cars and buildings, dimming glasses, and smart peep-proof films due to their switchable optical states under electrical fields as well as large area processibility. They are usually prepared with liquid crystals (LCs) and non-liquid crystalline monomers (NLCMs). Introduction of liquid crystalline monomers (LCMs) into PDLCs might spark new functionality or high-performance devices such as polymer-dispersed and -stabilized liquid crystals. In this study, the effect of molecular structures and doping concentrations of acrylate LCMs on the electro-optical properties and micro-structures of PDLC films is systematically studied. The pore size of polymer networks and the driving voltage of the PDLC films are affected by the molecular polarity and degree of functionality of the LCMs. The electro-optical properties of the PDLC films are affected by the synergistic influence of molecular structure of LCMs and micro-structures of PDLCs. These results might provide the experimental and theoretical basis for constructing the relationship between the molecular structure of LCM, micro-structure and electro-optical response of PDLC films.

We developed a microfluidic chip integrated with nucleic acid purification and droplet-based digital polymerase chain reaction (ddPCR) modules to realize a ‘sample-in, result-out’ infectious virus diagnosis. The whole process involved pulling magnetic beads through drops in an oil-enclosed environment. The purified nucleic acids were dispensed into microdroplets by a concentric-ring, oil–water-mixing, flow-focusing droplets generator driven under negative pressure conditions. Microdroplets were generated with good uniformity (CV = 5.8%), adjustable diameters (50–200 μm), and controllable flow rates (0–0.3 μL/s). Further verification was provided by quantitative detection of plasmids. We observed a linear correlation of R2 = 0.9998 in the concentration range from 10 to 105 copies/μL. Finally, this chip was applied to quantify the nucleic acid concentrations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The measured nucleic acid recovery rate of 75 ± 8.8% and detection limit of 10 copies/μL proved its on-chip purification and accurate detection abilities. This chip can potentially be a valuable tool in point-of-care testing.

Droplet ejection technology is widely used in green and intelligent manufacturing. A stable jetting can be defined as no obvious satellite droplets during the whole ejection process, which is of great importance to ensure the quality and efficiency of the printed products; However, due to the multi-parameter features and the interaction between different physics, using traditional analytical-based approaches to analyze and/or optimize is usually difficult and even unfeasible. Experimental tests using a PZT printhead design-optimization method based on surrogate modeling are proposed in this paper to overcome this challenge, which can synthesize the advantages of numerical simulation. The basic data for surrogate model construction was obtained by the Computational Fluid Dynamics (CFD) numerical-based model, which was developed to predict the flow characteristic under different parameter settings of the printhead. The accuracy of the developed numerical model was validated by performing experimental tests; thereby, the predictive ability of the numerical model in droplet ejection was verified. With the validated numerical model, the Design of Experiments (DoE) was performed to generate the necessary training and validation sample dataset required by the surrogate modeling. Thereafter, four surrogate modeling methods were adopted to construct the relationship between the design parameters and flow features, where the Kriging (KRG) was identified as the optimal modeling method. Based on the developed KRG model, global sensitivity analysis (GSA) of the parameters was carried out with Sobol’s method; thereby, the influence of different parameters can be quantified. Finally, a genetic algorithm (GA) was used to optimize the structure of the droplet printhead. Through validation, the optimized design model increases the droplet ejection speed by 20.84% while keeping no satellite droplet formation, confirming the efficient and stable printhead ejection, and verifying the feasibility and effectiveness of the analysis/optimization method proposed in this paper.

Cytidine is an antiviral and anticancer drug intermediate, its primary method of manufacture being fermentation. Uridine-cytidine kinase (UCK) catalyzes the reverse process of phosphorylation of cytidine to produce cytidylic acid, which influences cytidine accumulation in the Escherichia coli cytidine biosynthesis pathway. The cytidine-producing strain E. coli NXBG-11 was used as the starting strain in this work; the udk gene coding UCK was knocked out of the chromosomal genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology. The mutant strain E. coli NXBG-12 was obtained; its transcriptomics were studied to see how udk gene deletion affected cytidine synthesis and cell-wide transcription. The mutant strain E. coli NXBG-12 generated 1.28 times more cytidine than the original strain E. coli NXBG-11 after 40 h of shake-flask fermentation at 37 °C. The udk gene was knocked out, and transcriptome analysis showed that there were 1168 differentially expressed genes between the mutant and original strains, 559 upregulated genes and 609 downregulated genes. It was primarily shown that udk gene knockout has a positive impact on the cytidine synthesis network because genes involved in cytidine synthesis were significantly upregulated (p < 0.05) and genes related to the cytidine precursor PRPP and cofactor NADPH were upregulated in the PPP and TCA pathways. These results principally demonstrate that udk gene deletion has a favorable impact on the cytidine synthesis network. The continual improvement of cytidine synthesis and metasynthesis is made possible by this information, which is also useful for further converting microorganisms that produce cytidine.

Known as the “lung of the planet”, the Amazon rainforest produces more than 20% of the Earth’s oxygen. Once a carbon pool for mitigating climate change, the Brazilian Amazônia Biome recently has become a significant carbon emitter due to increasingly frequent wildfires. Therefore, it is of crucial importance for authorities to understand wildfire dynamics to manage them safely and effectively. This study incorporated remote sensing and spatial statistics to study both the spatial distribution of wildfires during 2019 and their relationships to 15 environmental and anthropogenic factors. First, broad-scale spatial patterns of wildfire occurrence were explored using kernel density estimation, Moran’s I, Getis-Ord Gi*, and optimized hot spot analysis (OHSA). Second, the relationships between wildfire occurrence and the environmental and anthropogenic factors were explored using several regression models, including Ordinary Least Squares (OLS), global (quasi) Poisson, Geographically-weighted Gaussian Regression (GWGR), and Geographically-weighted Poisson Regression (GWPR). The spatial analysis results indicate that wildfires exhibited pronounced regional differences in spatial patterns in the vast and heterogeneous territory of the Amazônia Biome. The GWPR model outperformed the other regression models and explained the distribution and frequency of wildfires in the Amazônia Biome as a function of topographic, meteorologic, and environmental variables. Environmental factors like elevation, slope, relative humidity, and temperature were significant factors in explaining fire frequency in localized hotspots, while factors related to deforestation (forest loss, forest fragmentation measures, agriculture) explained wildfire activity over much of the region. Therefore, this study could improve a comprehensive study on, and understanding of, wildfire patterns and spatial variation in the target areas to support agencies as they prepare and plan for wildfire and land management activities in the Amazônia Biome.

There is growing concern that chemotherapy drugs can damage Leydig cells and inhibit the production of testosterone. Increasing evidence shows that melatonin benefits the reproductive process. This study mainly explores the protective effect and possible molecular mechanism of melatonin regarding cisplatin-induced oxidative stress in testicular tissue and Leydig cells. We found that there were only Leydig and Sertoli cells in the testes of gastrointestinal tumor patients with azoospermia caused by platinum chemotherapeutic drugs. Melatonin (Mel) receptor 1/melatonin receptor 2 (MT1/MT2) was mainly expressed in human and mouse Leydig cells of the testes. We also observed that the melatonin level in the peripheral blood decreased and oxidative stress occurred in mice treated with cisplatin or gastrointestinal tumor patients treated with platinum-based chemotherapeutic drugs. iTRAQ proteomics showed that SIRT1/Nrf2 signaling and MT1 proteins were downregulated in cisplatin-treated mouse testes. The STRING database predicted that MT1 might be able to regulate the SIRT1/Nrf2 signaling pathway. Melatonin reduced oxidative stress and upregulated SIRT1/Nrf2 signaling in cisplatin-treated mouse testes and Leydig cells. Most importantly, after inhibiting MT1/MT2, melatonin could not upregulate SIRT1/Nrf2 signaling in cisplatin-treated Leydig cells. The MT1/MT2 inhibitor aggravated the cisplatin-induced downregulation of SIRT1/Nrf2 signaling and increased the apoptosis of Leydig cells. We believe that melatonin stimulates SIRT1/Nrf2 signaling by activating MT1/MT2 to prevent the cisplatin-induced apoptosis of Leydig cells.

Characterized by the high morbidity and mortality and seasonal surge, the influenza virus (IV) remains a major public health challenge. Oseltamivir is commonly used as a first-line antiviral. As a neuraminidase inhibitor, it attenuates the penetration of viruses through the mucus on the respiratory tract and inhibits the release of virus progeny from infected cells. However, over the years, oseltamivir-resistant strains have been detected in the IV surveillance programs. Therefore, new antivirals that circumvent the resistant strains would be of great importance. In this study, two novel secondary amine derivatives of oseltamivir CUHK326 (6f) and CUHK392 (10i), which bear heteroaryl groups of M2-S31 proton channel inhibitors, were designed, synthesized and subjected to biological evaluation using plaque assay. Influenza A virus (A/Oklahoma/447/2008, H1N1), influenza B viruses (B/HongKong/CUHK33261/2012), an oseltamivir-resistant influenza A virus (A/HongKong/CUHK71923/2009, H1N1) and an oseltamivir-resistant influenza B virus (B/HongKong/CUHK33280/2012) were included in the antiviral effect assessment compared to oseltamivir carboxylate (OC). Both novel compounds significantly reduced the plaque size of seasonal IV A and B, and performed similarly to OC at their corresponding half-maximal inhibitory concentration (IC50). CUHK392 (10i) functioned more effectively than CUHK326 (6f). More importantly, these compounds showed an inhibitory effect on the oseltamivir-resistant strain under 10 nM with selective index (SI) of >200.

Microfluidics offer microenvironments for reagent delivery, handling, mixing, reaction, and detection, but often demand the affiliated equipment for liquid control for these functions. As a helpful tool, the capillary pressure control valve (CPCV) has become popular to avoid using affiliated equipment. Liquid can be handled in a controlled manner by using the bubble pressure effects. In this paper, we analyze and categorize the CPCVs via three determining parameters: surface tension, contact angle, and microchannel shape. Finally, a few application scenarios and impacts of CPCV are listed, which includes how CPVC simplify automation of microfluidic networks, work with other driving modes; make extensive use of microfluidics by open channel, and sampling and delivery with controlled manners. The authors hope this review will help the development and use of the CPCV in microfluidic fields in both research and industry.

Chest X-rays (CXR) and computed tomography (CT) are the main medical imaging modalities used against the increased worldwide spread of the 2019 coronavirus disease (COVID-19) epidemic. Machine learning (ML) and artificial intelligence (AI) technology, based on medical imaging fully extracting and utilizing the hidden information in massive medical imaging data, have been used in COVID-19 research of disease diagnosis and classification, treatment decision-making, efficacy evaluation, and prognosis prediction. This review article describes the extensive research of medical image-based ML and AI methods in preventing and controlling COVID-19, and summarizes their characteristics, differences, and significance in terms of application direction, image collection, and algorithm improvement, from the perspective of radiologists. The limitations and challenges faced by these systems and technologies, such as generalization and robustness, are discussed to indicate future research directions.

Oseltamivir represents one of the most successful neuraminidase (NA) inhibitors in the current anti-influenza therapy. The 150-cavity of NA was identified as an additional binding pocket, and novel NA inhibitors have been designed to occupy the 150-cavity based on the structure information of oseltamivir carboxylate (OC) in complex with NA. In this study, a series of C-5-NH2-acyl derivatives of OC containing the pyrazole moiety were synthesized. Several derivatives exhibited substantial inhibitory activity against NA. Moreover, in silico ADME evaluation indicated that the derivatives were drug-like with higher oral absorption rates and greater cell permeability than OC. Additionally, molecular docking studies revealed that the derivatives interacted with both the NA enzyme active site and 150-cavity as expected. The results provided useful information for further structural optimization of OC.

A single-layer three-dimensional model was created to simulate multi-channel scanning of AlSi25 powder in selective laser melting (SLM) by the finite element method. Thermal behaviors of laser power and scanning speed in the procedure of SLM AlSi25 powder were studied. With the increase of laser power, the maximum temperature, size and cooling rate of the molten pool increase, while the scanning speed decreases. For an expected SLM process, a perfect molten pool can be generated using process parameters of laser power of 180 W and a scanning speed of 200 mm/s. The pool is greater than the width of the scanning interval, the depth of the molten pool is close to scan powder layer thickness, the temperature of the molten pool is higher than the melting point temperature of the powder and the parameters of the width and depth are the highest. To confirm the accuracy of the simulation results of forecasting excellent process parameters, the SLM experiment of forming AlSi25 powder was carried out. The surface morphology of the printed sample is intact without holes and defects, and a satisfactory metallurgical bond between adjacent scanning channels and adjacent scanning layers was achieved. Therefore, the development of numerical simulation in this paper provides an effective method to obtain the best process parameters, which can be used as a choice to further improve SLM process parameters. In the future, metallographic technology can also be implemented to obtain the width-to-depth ratio of the SLM sample molten pool, enhancing the connection between experiment and theory.

To minimize treatment toxicities, recent anti-cancer research efforts have switched from broad-based chemotherapy to targeted therapy, and emerging data show that altered cellular metabolism in cancerous cells can be exploited as new venues for targeted intervention. In this study, we focused on, among the altered metabolic processes in cancerous cells, altered glycosylation due to its documented roles in cancer tumorigenesis, metastasis and drug resistance. We hypothesize that the enzymes required for the biosynthesis of UDP-hexoses, glycosyl donors for glycan synthesis, could serve as therapeutic targets for cancers. Through structure-based virtual screening and kinetic assay, we identified a drug-like chemical fragment, GAL-012, that inhibit a small family of UDP-hexose pyrophosphorylases-galactose pyro-phosphorylase (GALT), UDP-glucose pyrophosphorylase (UGP2) and UDP-N-acetylglucosamine pyrophosphorylase (AGX1/UAP1) with an IC50 of 30 µM. The computational docking studies supported the interaction of GAL-012 to the binding sites of GALT at Trp190 and Ser192, UGP2 at Gly116 and Lys127, and AGX1/UAP1 at Asn327 and Lys407, respectively. One of GAL-012 derivatives GAL-012-2 also demonstrated the inhibitory activity against GALT and UGP2. Moreover, we showed that GAL-012 suppressed the growth of PC3 cells in a dose-dependent manner with an EC50 of 75 µM with no effects on normal skin fibroblasts at 200 µM. Western blot analysis revealed reduced expression of pAKT (Ser473), pAKT (Thr308) by 77% and 72%, respectively in the treated cells. siRNA experiments against the respective genes encoding the pyrophosphorylases were also performed and the results further validated the proposed roles in cancer growth inhibition. Finally, synergistic relationships between GAL-012 and tunicamycin, as well as bortezomib (BTZ) in killing cultured cancer cells were observed, respectively. With its unique scaffold and relatively small size, GAL-012 serves as a promising early chemotype for optimization to become a safe, effective, multi-target anti-cancer drug candidate which could be used alone or in combination with known therapeutics.

Novel antimicrobial classes are in desperate need for clinical management of infections caused by increasingly prevalent multi-drug resistant pathogens. The protein-protein interaction between bacterial RNA polymerase (RNAP) and the housekeeping sigma initiation factor is essential to transcription and bacterial viability. It also presents a potential target for antimicrobial discovery, for which a hit compound (C3) was previously identified from a pharmacophore model-based in silico screen. In this study, the hit compound was experimentally assessed with some rationally designed derivatives for the antimicrobial activities, in particular against Streptococcus pneumoniae and other pathogens. One compound, C3-005, shows dramatically improved activity against pneumococci compared to C3. C3-005 also attenuates S. pneumoniae toxin production more strongly than existing classes of antibiotics tested. Here we demonstrate a newly validated antimicrobial agent to address an overlooked target in the hit-to-lead process, which may pave the way for further antimicrobial development.

Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives 7–26 were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains (B. subtilis 168, S. aureus RN4220, E. coli DH5α, A. baum ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds 7–14, showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound 22 exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 μg/mL against MRSA USA300 and 4 μg/mL against B. subtilis. The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.