Unveiling Drimenol: A Phytochemical with Multifaceted Bioactivities.

Drimenol, a phytochemical with a distinct odor is found in edible aromatic plants, such as Polygonum minus (known as kesum in Malaysia) and Drimys winteri. Recently, drimenol has received increasing attention owing to its diverse biological activities. This review offers the first extensive overview of drimenol, covering its sources, bioactivities, and derivatives. Notably, drimenol possesses a wide spectrum of biological activities, including antifungal, antibacterial, anti-insect, antiparasitic, cytotoxic, anticancer, and antioxidant effects. Moreover, some mechanisms of its activities, such as its antifungal effects against human mycoses and anticancer activities, have been investigated. However, there are still several crucial issues in the research on drimenol, such as the lack of experimental understanding of its pharmacokinetics, bioavailability, and toxicity. By synthesizing current research findings, this review aims to present a holistic understanding of drimenol, paving the way for future studies and its potential utilization in diverse fields.

5-Fluorouracil in Combination with Calcium Carbonate Nanoparticles Loaded with Antioxidant Thymoquinone against Colon Cancer: Synergistically Therapeutic Potential and Underlying Molecular Mechanism.

Colon cancer is the third most common cancer worldwide, with high mortality. Adverse side effects and chemoresistance of the first-line chemotherapy 5-fluorouracil (5-FU) have promoted the widespread use of combination therapies. Thymoquinone (TQ) is a natural compound with potent antioxidant activity. Loading antioxidants into nano delivery systems has been a major advance in enhancing their bioavailability to improve clinical application. Hence, this study aimed to prepare the optimal TQ-loaded calcium carbonate nanoparticles (TQ-CaCO3 NPs) and investigate their therapeutic potential and underlying molecular mechanisms of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Firstly, we developed purely aragonite CaCO3 NPs with a facile mechanical ball-milling method. The pH-sensitive and biocompatible TQ-CaCO3 NPs with sustained release properties were prepared using the optimal synthesized method (a high-speed homogenizer). The in vitro study revealed that the combination of TQ-CaCO3 NPs (15 µM) and 5-FU (7.5 µM) inhibited CT26 cell proliferation and migration, induced cell apoptosis and cell cycle arrest in the G0/G1 phase, and suppressed the CT26 spheroid growth, exhibiting a synergistic effect. Finally, network pharmacology and molecular docking results indicated the potential targets and crucial signaling pathways of TQ-CaCO3 NPs in combination with 5-FU against colon cancer. Therefore, TQ-CaCO3 NPs combined with 5-FU could enhance the anti-colon cancer effects of 5-FU with broader therapeutic targets, warranting further application for colon cancer treatment.

Exploring the Therapeutic Potential of 5-Fluorouracil-Loaded Calcium Carbonate Nanoparticles Combined with Natural Compound Thymoquinone for Colon Cancer Treatment.

Given the need for novel and effective therapies for colon cancer, this study aimed to investigate the effects of 5-fluorouracil-loaded calcium carbonate nanoparticles (5FU-CaCO3np) combined with thymoquinone (TQ) against colon cancer. A shaking incubator and a high-speed homogenizer were used to prepare the optimal 5FU-CaCO3np, with characterizations of physicochemical properties, in vitro drug release profile, and biocompatibility. In vitro experiments and molecular docking were employed to evaluate the therapeutic potential of the combination for colon cancer treatment. Study results revealed that 5FU-CaCO3np with a size of approximately 130 nm was synthesized using the high-speed homogenizer. Its favorable biocompatibility, pH sensitivity, and sustained release properties facilitated reduced toxic side effects of 5-FU on NIH3T3 normal cells and enhanced inhibitory effects on CT26 colon cancer cells. The combination of 5FU-CaCO3np (1.875 µM) and TQ (30 µM) showed significantly superior anti-colon cancer effects to 5FU-CaCO3np alone in terms of cell proliferation and migration inhibition, cell apoptosis induction, and spheroid growth suppression in CT26 cells (p < 0.05), with strong interactions between the drugs and targets (E-cadherin, Bcl-2, PCNA, and MMP-2). These results provide evidence for 5FU-CaCO3np as a novel regimen against colon cancer. Combining 5FU-CaCO3np and TQ may offer a new perspective for colon cancer therapy.

Accurate and fast implementation of soybean pod counting and localization from high-resolution image.

Introduction: Soybean pod count is one of the crucial indicators of soybean yield. Nevertheless, due to the challenges associated with counting pods, such as crowded and uneven pod distribution, existing pod counting models prioritize accuracy over efficiency, which does not meet the requirements for lightweight and real-time tasks. Methods: To address this goal, we have designed a deep convolutional network called PodNet. It employs a lightweight encoder and an efficient decoder that effectively decodes both shallow and deep information, alleviating the indirect interactions caused by information loss and degradation between non-adjacent levels. Results: We utilized a high-resolution dataset of soybean pods from field harvesting to evaluate the model's generalization ability. Through experimental comparisons between manual counting and model yield estimation, we confirmed the effectiveness of the PodNet model. The experimental results indicate that PodNet achieves an R2 of 0.95 for the prediction of soybean pod quantities compared to ground truth, with only 2.48M parameters, which is an order of magnitude lower than the current SOTA model YOLO POD, and the FPS is much higher than YOLO POD. Discussion: Compared to advanced computer vision methods, PodNet significantly enhances efficiency with almost no sacrifice in accuracy. Its lightweight architecture and high FPS make it suitable for real-time applications, providing a new solution for counting and locating dense objects.

Accurate method for correcting the translation position error of ptychography based on quantum particle swarm optimization.

In ptychography, the translation position error will cause the periodic grid deviation and tremendously decrease the reconstruction quality. It is crucial to attain the precise translation position of the probe with respect to the object. The current correction methods may fall into a local optimal value, and miss the better results. An accurate method based on the quantum particle swarm optimization is proposed to globally correct the translation position error and add the randomness to avoid trapping in local optimum. In our proposed method, particles in a quantum bound state can appear at any point in the solution space with a certain probability density. In order words, the corrected translation position can be spread over the searching space, which can acquire the possibility of jumping out of the local optimum. Experiments are conducted to verify that our proposed method can be used to enhance the correction accuracy of the translation position error as well as avoid local optimum.

Phase retrieval for single-frame interferogram with an irregular-shaped aperture based on deep learning.

This paper proposes a high-precision phase retrieval method based on deep learning to extract the Zernike coefficients from a single-frame interferogram with an irregular-shaped aperture. Once the Zernike coefficients are obtained, the phase distribution can be retrieved directly using the Zernike polynomials. For many apertures, the root mean square (RMS) of the residual wavefront between the true and estimated wavefronts reached the order of 10-3 λ. Simulations were conducted under different noise conditions, indicating that the proposed method has high measurement accuracy and robustness. Experiments demonstrated that the accuracy achieved by this method was comparable to that of commercial phase-shifting interferometers. We believe that this method is useful for measuring optical surfaces with irregular apertures.

Wavefront-splitting interferometer based on orbital angular momentum beams.

Orbital angular momentum (OAM) interferometers have attracted great attention in metrology. However, OAM interferometers usually have large sizes and are difficult to align. OAM-based wavefront-splitting interferometer (WSI-OAM) can achieve nano-displacement measurement with compact size and easy to align. In this manuscript, we propose and demonstrate a nano-displacement measurement system based on WSI-OAM. A resolution of 0.1 nm with an uncertainty of 0.013 nm is achieved with measurement accuracy higher than 99.87% and linearity close to 99%. This work offers a practical approach to miniaturize and integrate OAM interferometers in metrology.

Comprehensive characterization of B7 family members in NSCLC and identification of its regulatory network.

B7 family members act as co-stimulatory or co-inhibitory molecules in the adaptive immune system. Thisstudy aimed to investigate the dysregulation, prognostic value and regulatory network of B7 family members in non-small cell lung cancer (NSCLC). Data for lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients were extracted from public databases. Patient prognosis was determined by Kaplan-Meier analysis. The downstream signaling pathways of B7 family were identified via GO and KEGG analysis. The key B7 related genes were selected by network, correlation and functional annotation analysis. Most B7 family members were dysregulated in LUAD and LUSC. The expression of B7-1/2/H3 and B7-H5 were significantly associated with overall survival in LUAD and LUSC, respectively. The major pathway affected by B7 family was the EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway. MAPK1, MAPK3 and MAP2K1 were pivotal B7 related genes in both LUAD and LUSC. This study reveals an overall dysregulation of B7 family members in NSCLC and highlights the potential of combination use of tyrosine kinase inhibitors or MEK/ERK inhibitors with B7 member blockade for NSCLC treatment.

The Role of Mesenchymal Stem Cells in Cancer Immunotherapy.

Mesenchymal stem cells (MSCs) are getting attention in the field of cancer immunotherapy. The main effects of MSCs on tumors are homing and regulation of inflammatory and immune responses. Indeed, cancer immunotherapy has become a promising treatment and MSCs play a potential role in regulating the efficacy of immunotherapy. In addition, MSCs are an ideal carrier for immunomodulatory protein transmission. As such MSCs combined with immunotherapy drugs could act synergistically against tumors, throwing a great impact on cancer therapy. And MSCs may have potential in the treatment of cytokine storm or cytokine release syndrome (CRS). It is assumed that MSCs can form chimeric antigen receptor MSCs (CAR-MSCs). Whether CAR-MSCs can provide a new idea of cancer immunotherapy is unknown. It is a prime time to review the latest progress of MSCs in cancer immunotherapy, in order to clarify to fully understand the role of MSCs in cancer therapy in clinical practice.

Weighted Gene Co-Expression Network Analysis of Immune Infiltration in Nonalcoholic Fatty Liver Disease.

BACKGROUND: Immune cell infiltration is an important component of nonalcoholic fatty liver disease (NAFLD) pathogenesis. This study aimed to explore novel genes associated with immune infiltration in the progression of NAFLD. METHODS: CIBERSORT was used to evaluate the abundance of immune infiltration in the human NAFLD via a high-throughput sequencing dataset. Further weighted gene co-expression network analysis (WGCNA) was performed to search for the susceptibility gene module and hub genes associated with differential immune cells. The expression of hub genes in different liver non-parenchymal cell clusters and NAFLD-associated hepatocellular carcinoma (HCC) was also explored. RESULTS: Four hub genes (ITGBL1, SPINT1, COL1A2, and THBS2) were ultimately identified, which may be associated with immune infiltration, fibrosis progression, and activity score. The receiver operating characteristic curve (ROC) analysis suggested that these genes had good predictive value for NASH and advanced fibrosis. A single-cell analysis showed that COL1A2 was highly expressed in hepatic stellate cells (HSCs), especially in the later stage, while SPINT1 was highly expressed in cholangiocytes (Cho). In addition, ITGBL1, COL1A2, and THBS2 might be associated with transforming from nonalcoholic steatohepatitis (NASH) to HCC. Our findings identified several novel genes that might be related to immune infiltration in NAFLD. CONCLUSION: These genes may serve as potential markers for the assessment of immune infiltration as well as therapeutic targets for NAFLD. More studies are needed to elucidate the biological mechanism of these genes in the occurrence and development of NAFLD.

Clinical response to belumosudil in bronchiolitis obliterans syndrome: a combined analysis from 2 prospective trials.

Chronic graft-versus-host disease (cGVHD) of the lung, or bronchiolitis obliterans syndrome (BOS), is a high-risk disease manifestation associated with poor outcomes. Currently available treatments have demonstrated limited clinical efficacy in this setting. Belumosudil is a novel oral selective rho-associated coiled-coil-containing protein kinase-2 inhibitor that was recently approved by the US Food and Drug Administration in the treatment of cGVHD. We identified 59 subjects with BOS who were enrolled and treated in 2 prospective clinical trials of belumosudil. Patients with BOS had a percentage predicted forced expiratory volume in 1 second (FEV1) of ≤79% at enrollment and clinician attribution of lung disease owing to cGVHD. The National Institutes of Health (NIH) cGVHD lung scores at enrollment were 1 (n = 30, 59%), 2 (n = 23, 39%), or 3 (n = 6, 10%). According to NIH response criteria, the best overall response rate (ORR) for lung cGVHD was 32% (partial response: 17%; complete response: 15%). Response rates were inversely proportional to baseline NIH GVHD lung score at enrollment (lung score 1: ORR 50%; lung score 2: ORR 17%, lung score 3: ORR 0%) (P = .006). In multivariable analysis, male sex, lower baseline NIH cGVHD lung score, and partial response to previous line of cGVHD therapy before enrollment were associated with higher rates of lung-specific response. No significant correlation was identified between pulmonary function evaluations and measures of patient symptoms (NIH lung symptom score or Lee Symptom Scale score for lung). In conclusion, belumosudil treatment was associated with lung-specific clinical responses for subjects with BOS, which were more commonly observed in less advanced disease. Optimization of treatment response evaluations remains a challenge in patients with BOS.

Transcriptome analysis of peripheral blood mononuclear cells in patients with type 1 diabetes mellitus.

PURPOSE: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic ß cells. The goal of this study was to explore potential biological biomarkers for T1DM. METHODS: Two microarray datasets (GSE55098 and GSE156035) about human peripheral blood mononuclear cells (PBMCs) were systematically extracted from the Gene Expression Omnibus (GEO) database. Common genes were identified from the perspective of differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) respectively, and hub genes were identified by least absolute shrinkage and selection operator (LASSO) analysis. We also observed the expression of these hub genes in some common autoimmune diseases and predicted transcription factors (TFs) that might be associated with these genes. RESULTS: Seven hub genes (DDIT4, ESCO2, SH3BP4, PRICKLE1, EPM2AIP1, KCNJ15 and GRM8) were finally identified. Receiver operating characteristic (ROC) analysis showed that the high expression of these genes could well predict the occurrence of T1DM. Gene set enrichment analysis (GSEA) suggested that most of these hub genes may be mainly involved in the changes of biological functions such as inflammation, infection, immunity, cancer, and apoptosis. Further, compared with the control group, the expression levels of these hub genes also changed in some other autoimmune diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary biliary cholangitis (PBC), etc., indicating that they might be the common targets of these autoimmune diseases. CONCLUSIONS: The present study identified novel genes associated with T1DM from the PBMCs perspective that might provide new ideas for the early diagnosis, monitoring, evaluation, and prediction of T1DM.

Effect of prior thyroid cancer on survival of primary liver cancer: a study based on the SEER database.

To explore the effect of prior thyroid cancer on the survival of primary liver cancer (PLC). Eligible PLC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database during 2004-2016. Propensity score matching (PSM) was used to create a highly comparable control group that PLC patients without prior thyroid cancer. All PLC patients were divided into three groups based on the survival information: (1) PLC-specific death; (2) death due to other causes; (3) alive. The effect sizes were presented by the corresponding hazard ratio (HR) and 95% confidence intervals (CI). Totally, 142 PLC patients with prior thyroid cancer and 1420 PLC patients without prior thyroid cancer were included. During the follow-up period, 714 (45.71%) PLC patients died of liver cancer while 638 (40.85%) PLC patients were alive. Median survival time for PLC patients was 11.00 months, respectively. PLC patients with prior thyroid cancer have a lower risk of death (HR = 0.64; 95% CI: 0.48-0.86). Subgroup analyses stratified by gender displayed the similar relation in female patients with PLC. Prior thyroid cancer may be a protective factor for liver cancer death in PLC patients, especially in female patients.

Correlation of Patient-Reported Outcomes with Clinical Organ Responses: Data from the Belumosudil Chronic Graft-versus-Host Disease Studies.

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT) owing to both the disease itself and the immunosuppressive agents used for treatment. Response criteria endorsed by the National Institutes of Health (NIH) Consensus Conference on Clinical Trials in chronic GVHD include both clinician-documented measures and patient-reported outcomes (PROs) since both are considered clinical benefits by the Food and Drug Administration. The correlation between clinically assessed responses in organs and PRO improvements in organ-specific symptoms has not been investigated in depth. We used data from 2 published studies of belumosudil, an oral rho-associated coiled-coil-containing protein kinase-2 (ROCK2) inhibitor, for chronic GVHD to test the correlation between clinical and PRO outcomes. Participants completed PROs at enrollment and every 1 to 2 cycles according to the study design. Individual organ responses (complete plus partial response) and clinically meaningful changes in PROs were defined according to published methods. Generalized estimating equation methods were used to correlate changes in PROs associated with clinical responses according to NIH criteria, accounting for missing information and repeated measures. Data from all doses in both trials were included without stratification. The liver and genital tract were not included owing to a lack of site-specific PROs. Our pooled analysis of clinical and PRO data included 170 patients enrolled in 2 belumosudil studies (NCT02841995, n = 54; NCT03640481, n = 132) for whom we had baseline PROs, at least 1 follow-up PRO, and at least 1 response assessment. There was a strong positive correlation between complete and partial organ and overall responses and changes in PRO symptom scores, as well as clinically meaningful improvements. For all organs except joints, esophagus, and lower gastrointestinal tract, there was at least 1 PRO statistically correlated with NIH organ response. These data support the use of PROs for response assessment to document clinically meaningful benefit in chronic GVHD clinical trials.

Co-phase state detection for segmented mirrors by dual-wavelength optical vortex phase-shifting interferometry.

The application of large-aperture telescopes requires the support of co-phase measurement techniques for segmented mirrors. This paper proposes a novel method to detect the co-phase state of segmented mirrors by applying a dual-wavelength phase-shifting interferometer based on optical vortex. Theory and experiments indicate that the wrapped phase map edges obtained by phase-shifting interference of the vortex beam are distributed in the form of a Fermat spiral. The piston error of the segmented mirrors corresponds to the rotation of the standard Fermat spiral center. In contrast, the tip/tilt error corresponds to the alteration of the center position of the deformed Fermat spiral. The rotation angle and the center position of the spiral are obtained by curve fitting, and the co-phase errors can be inversely solved. The experiments achieved an accuracy of approximately 4.04 nm in the piston and 0.16″ in the tip/tilt. The method avoids using complex lens arrays and devices, has an extended measurement range, high accuracy, and allows the co-phase errors between all sub-mirrors to be obtained in real-time. This study provides a novel and general method for detecting co-phase errors in a segmented primary mirror.

Current Understanding and Future Perspectives on Hyperprogressive Disease Highlight the Tumor Microenvironment.

Cancer immunotherapy with immune checkpoint inhibitors has revolutionized traditional cancer therapy. Although many patients have achieved long-term survival benefits from treatment with immune checkpoint inhibitors, there are still some patients who develop rapid tumor progression after immunotherapy, known as HPD. Here, we summarize the current knowledge on HPD after treatment with immune checkpoint inhibitors to promote a more thorough understanding of the disease. This review focuses on multiple aspects of HPD, especially the tumor microenvironment, with the hope that more reliable biomarkers and therapeutics will be established for HPD in the future.

Directly Printed Embedded Metal Mesh for Flexible Transparent Electrode via Liquid Substrate Electric-Field-Driven Jet.

Flexible transparent electrodes (FTEs) with embedded metal meshes play an indispensable role in many optoelectronic devices due to their excellent mechanical stability and environmental adaptability. However, low-cost, simple, efficient, and environmental friendly integrated manufacturing of high-performance embedded metal meshes remains a huge challenge. Here, a facile and novel fabrication method is proposed for FTEs with an embedded metal mesh via liquid substrateelectric-field-driven microscale 3D printing process. This direct printing strategy avoids tedious processes and offers low-cost and high-volume production, enabling the fabrication of high-resolution, high-aspect ratio embedded metal meshes without sacrificing transparency. The final manufactured FTEs with 80 mm × 80 mm embedded metal mesh offers excellent optoelectronic performance with a sheet resistance (Rs ) of 6 Ω sq-1 and a transmittance (T) of 85.79%. The embedded metal structure still has excellent mechanical stability and good environmental suitability under different harsh working conditions. The practical feasibility of the FTEs is successfully demonstrated with a thermally driven 4D printing structure and a resistive transparent strain sensor. This method can be used to manufacture large areas with facile, high-efficiency, low-cost, and high-performance FTEs.

3D Printed High Performance Silver Mesh for Transparent Glass Heaters through Liquid Sacrificial Substrate Electric-Field-Driven Jet.

Transparent glass with metal mesh is considered a promising strategy for high performance transparent glass heaters (TGHs). However, the realization of simple, low-cost manufacture of high performance TGHs still faces great challenges. Here, a technique for the fabrication of high performance TGHs is proposed using liquid sacrificial substrate electric-field-driven (LS-EFD) microscale 3D printing of thick film silver paste. The liquid sacrificial substrate not only significantly improves the aspect ratio (AR) of silver mesh, but also plays a positive role in printing stability. The fabricated TGHs with a line width of 35 µm, thickness of 12.3 µm, and pitch of 1000 µm exhibit a desirable optoelectronic performance with sheet resistance (Rs ) of 0.195 Ω sq-1 and transmittance (T) of 88.97%. A successful deicing test showcases the feasibility and practicality of the manufactured TGHs. Moreover, an interface evaporator is developed for the coordination of photothermal and electrothermal systems based on the high performance TGHs. The vapor generation rate of the device reaches 10.69 kg m-2 h-1 with a voltage of 2 V. The proposed technique is a promising strategy for the cost-effective and simple fabrication of high performance TGHs.

Imaging performance of a mid-infrared metalens with a machining error.

Metalenses exhibit excellent performance as a new type of optical element; mid-infrared devices based on metalenses are advantageous to numerous applications in biomedical, military and industrial fields. The demand for large-area and high-efficiency mid-infrared metalenses has increased in recent years. However, the current processing methods for metalens production introduce different types of processing errors. Therefore, qualitative analyses of various errors that may exist in the processing of metalenses should be performed. In this study, we use the finite-difference time-domain calculation method and introduce various typical errors into a transmission phase-based mid-infrared metalens for simulation and analysis. The simulation results show that the defects caused by these processes affect focusing efficiency, and that some defects affect the quality of light. Subsequently, we prepare a metalens within the allowable error range and test its optical performances. The experiment confirms the excellent imaging performance of our metalens. Our study can help manufacturers identify defects to improve manufacturing processes, thereby enabling the incorporation of metalenses in industrial applications.

Corrigendum: Metagenome Analysis of Intestinal Bacteria in Healthy People, Patients With Inflammatory Bowel Disease and Colorectal Cancer.

[This corrects the article DOI: 10.3389/fcimb.2021.599734.].