An ultrasound-based ensemble machine learning model for the preoperative classification of pleomorphic adenoma and Warthin tumor in the parotid gland.

OBJECTIVES: The preoperative classification of pleomorphic adenomas (PMA) and Warthin tumors (WT) in the parotid gland plays an essential role in determining therapeutic strategies. This study aims to develop and validate an ultrasound-based ensemble machine learning (USEML) model, employing nonradiative and noninvasive features to differentiate PMA from WT. METHODS: A total of 203 patients with histologically confirmed PMA or WT who underwent parotidectomy from two centers were enrolled. Clinical factors, ultrasound (US) features, and radiomic features were extracted to develop three types of machine learning model: clinical models, US models, and USEML models. The diagnostic performance of the USEML model, as well as that of physicians based on experience, was evaluated and validated using receiver operating characteristic (ROC) curves in internal and external validation cohorts. DeLong's test was used for comparisons of AUCs. SHAP values were also utilized to explain the classification model. RESULTS: The USEML model achieved the highest AUC of 0.891 (95% CI, 0.774-0.961), surpassing the AUCs of both the US (0.847; 95% CI, 0.720-0.932) and clinical (0.814; 95% CI, 0.682-0.908) models. The USEML model also outperformed physicians in both internal and external validation datasets (both p < 0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of the USEML model and physician experience were 89.3%/75.0%, 87.5%/54.2%, 87.5%/65.6%, and 89.3%/65.0%, respectively. CONCLUSIONS: The USEML model, incorporating clinical factors, ultrasound factors, and radiomic features, demonstrated efficient performance in distinguishing PMA from WT in the parotid gland. CLINICAL RELEVANCE STATEMENT: This study developed a machine learning model for preoperative diagnosis of pleomorphic adenoma and Warthin tumor in the parotid gland based on clinical, ultrasound, and radiomic features. Furthermore, it outperformed physicians in an external validation dataset, indicating its potential for clinical application. KEY POINTS: • Differentiating pleomorphic adenoma (PMA) and Warthin tumor (WT) affects management decisions and is currently done by invasive biopsy. • Integration of US-radiomic, clinical, and ultrasound findings in a machine learning model results in improved diagnostic accuracy. • The ultrasound-based ensemble machine learning (USEML) model consistently outperforms physicians, suggesting its potential applicability in clinical settings.

Integrated Anionic Zirconium-Organic Cage and Cationic Boron-Imidazolate Cage for Synergetic Optical Limiting.

Making oppositely charged metal-organic cages (MOCs) into a tightly ordered structure may bring interesting functions. Herein, we report a novel structure composed of anionic (Zr4 L6 )8- (L=embonate) tetrahedral cages and in situ-formed cationic [Zn4 (Bim)4 ]4+ (Bim=[BH(im)3 ]- ; im=imidazole) cubic cages. Chiral transfer is observed from enantiopure (Zr4 L6 )8- cage to enantiopure [Zn4 (Bim)4 ]4+ cage. A pair of enantiomers (PTC-373(Δ) and PTC-373(Λ)) are formed. PTC-373 exhibits high chemical and thermal stabilities, affording an interesting single-crystal-to-single-crystal transformation. More importantly, the combination of ionic pair cages significantly enhances its third-order nonlinear optical property, and its thin-film exhibits an excellent optical limiting effect.

Ultraviolet Nonlinear Optical Single Crystals of A Three-Dimensional Chiral Covalent Framework Containing Te-O-B-O Bonds.

Extending covalent organic frameworks (COFs) into crystalline carbon-free covalent backbones is an important strategy to endow these materials with more exotic functions. Integrating metal-free inorganic and organic components into one covalent framework is an effective way to address the issue of poor thermal/solvent stability in the field of nonlinear optics (NLO). However, constructing such structures is very challenging. Here, we linked 3-connected nods (BO3) and 2-connected organic building blocks (Te(Ph)2) together to produce colorless single crystals (size up to 400 µm) of a three-dimensional (3D) chiral covalent framework (CityU-22). The single-crystal X-ray diffraction (SCXRD) analysis reveals that CityU-22 has a non-carbon Te-O-B-O bond-based network with the srs topology. The chiral CityU-22 displays good stability under the treatment of different common solvents or heat (the decomposition temperature above 300 °C). Due to its non-π-conjugated backbone (-Te-O-B-O-), CityU-22 shows an ultraviolet NLO behavior with a second-harmonic generation (SHG) response similar to KH2PO4 (KDP).

Standardizing image assessment in optical diffraction tomography.

Optical diffraction tomography (ODT) has gradually become a popular label-free imaging technique that offers diffraction-limited resolution by mapping an object's three-dimensional (3D) refractive index (RI) distribution. However, there is a lack of comprehensive quantitative image assessment metrics in ODT for studying how various experimental conditions influence image quality, and subsequently optimizing the experimental conditions. In this Letter, we propose to standardize the image assessment in ODT by proposing a set of metrics, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and structural distinguishability (SD). To test the feasibility of the metrics, we performed experiments on angle-scanning ODT by varying the number of illumination angles, RI contrast of samples, sample feature sizes, and sample types (e.g., standard polystyrene beads and 3D printed structures) and evaluated the RI tomograms with SNR, CNR, and SD. We further quantitatively studied how image quality can be improved, and tested the image assessment metrics on subcellular structures of living cells. We envision the proposed image assessment metrics may greatly benefit end-users for assessing the RI tomograms, as well as experimentalists for optimizing ODT instruments.

Complex wave and phase retrieval from a single off-axis interferogram.

Single-frame off-axis holographic reconstruction is promising for quantitative phase imaging. However, reconstruction accuracy and contrast are degraded by noise, frequency spectrum overlap of the interferogram, severe phase distortion, etc. In this work, we propose an iterative single-frame complex wave retrieval based on an explicit model of object and reference waves. We also develop a phase restoration algorithm that does not resort to phase unwrapping. Both simulation and real experiments demonstrate higher accuracy and robustness compared to state-of-the-art methods, for both complex wave estimation and phase reconstruction. Importantly, the allowed bandwidth for the object wave is significantly improved in realistic experimental conditions (similar amplitudes for object and reference waves), which makes it attractive for large field-of-view and high-resolution imaging applications.

Curative Effect and Mechanisms of Radix Arnebiae Oil on Burn Wound Healing in Rats.

Radix arnebiae oil (RAO) is a clinically useful traditional Chinese medical formula with outstanding curative effects on burns. However, the mechanism of the effect of RAO on wound healing remains unclear. The present study investigates the molecular mechanisms of the potential curative effect of RAO on wound healing. The concentrations of the main constituents, shikonin, imperatorin, and ferulic acid in RAO detected by HPLC were 24.57, 3.15, and 0.13 mg/mL, respectively. A rat burn model was established, and macroscopic and histopathological studies were performed. RAO significantly accelerated wound closure and repair scarring, increased superoxide dismutase activities, and reduced malondialdehyde. RAO also downregulated interleukin (IL)-6, IL-1ß and tumor necrosis factor-α in wound tissues and increased secretion of vascular endothelial growth factor, epidermal growth factor, and transforming growth factor (TGF)-ß1. RAO increased the gene expression of TGF-ß1, type I and III collagen, and increased the protein expression of TGF-ß1 and phosphorylation of PI3K and Akt. In conclusion, RAO likely promotes wound healing via antioxidant and anti-inflammatory activities and increases re-epithelization. Activation of the TGF-ß1/PI3K/Akt pathway may play an important role in the healing efficacy of RAO. These findings suggest that RAO could be a promising alternative local treatment for burn wound healing.

Selected ssDNA aptamers-graphene oxide-based fluorescent biosensor to detect sulfameter in milk.

The abuse of sulfameter (SME) in animal husbandry can cause drug resistance and toxic or allergic reactions in humans. Therefore, it is very important to establish a simple, inexpensive, and efficient method for detecting SME in food. In this work, we propose a single fluorescent aptamer/graphene oxide (GO)-based biosensor to detect SME residues in milk. Aptamers that specifically bind to SME were screened using capture-SELEX and a ssDNA library immobilized on magnetic beads. The 68 active candidate aptamers were chemically synthesized for specificity and affinity characterization. Among the aptamers, the aptamer sulf-1 revealed the highest affinity (Kd = 77 ± 15 nM) to SME and was selected to construct a GO-based fluorescent biosensor for real milk sample detection. Under optimal conditions, the single fluorescent aptasensor had a wide linear range (R2 was 0.997) from 7 to 336 ng/ml and a low detection limit of 3.35 ng/ml that was calculated with a 3SD/slope. The single fluorescent method was also validated using SME-fortified milk samples, showing average recoveries ranging from 99.01% to 104.60% with a relative standard deviation of less than 3.88%. These results demonstrate that this novel aptamer sensor provides an opportunity for sensitive, convenient, and accurate detection of SME residues in milk.

The component of the Chamaecyparis obtusa essential oil and insecticidal activity against Tribolium castaneum (Herbst).

Tribolium castaneum (Herbst) is a worldwide grain storage pest controlled by chemical control methods of phosphine fumigation, which results in many hazards, damages human health, makes pests resistant to pesticides, and pollutes the environment. In recent years, the popularity of botanical insecticides has continued to rise, and plant essential oils (EO) are considered potential alternatives for developing insecticides. In the current study, we selected the Chamaecyparis obtusa EO to determine its insecticidal effects and component analysis on T. castaneum. Through gas chromatography-ion mobility spectrometry (GC-IMS) technology, cedrol was the most obvious compound in the signal peak of the volatile components detected in the C. obtusa EO. The results of the bioassay showed that the C. obtusa EO had certain contact activity against T. castaneum, and the LD50 was 52.54 µg/adult. At three concentrations (0.41,1.62, 2.83 uL/cm2), the repellent rates of C. obtusa EO against T. castaneum were all above 80% at 15, 30, 60, and 120 min, respectively, indicating that the repellent effect was strong. Meanwhile, the C. obtusa EO exhibited fumigant toxicity against T. castaneum with LC50 values of 7.09 µg/L air. In addition, C. obtusa EO significantly increased the activity of AChE, CarE, POD, CAT, T-SOD, and chitinase in T. castaneum. Finally, the mechanism of C. obtusa EO on T. castaneum adults was explored based on transcriptome sequencing. We found that the DEGs focused on the chitin metabolic process and some aging genes in T. castaneum. Therefore, C. obtusa EO could be used as potential eco-friendly candidates for stored grain pest management.

Calibration Method of a Wideband AC Resistance Voltage Divider Based on an Equivalent Model.

Aiming at the problem of large measurement error and phase shift in resistance voltage dividers under high-frequency conditions in the field of power measurement, such as power harmonics, an error correction method is proposed for an alternating current (AC) resistance voltage divider based on the equivalence principle. Firstly, the frequency error model of the AC resistance voltage divider precision is established, and the angle difference of the continuous spectrum ratio difference from 50 Hz to 100 kHz is corrected by determining the shielding structure and the resistance parameters and fine-tuning the shielding potential correction method to reduce the capacities error of the AC resistance voltage divider design precision. At the same time, the performance parameters such as the direction and magnitude of the shielding potential compensation capacitive error are investigated. Finally, the precision voltage divider (the maximum voltage applied is 480 V) calibration experiments verify that the important characteristic judgment factor of the voltage divider is independent of the frequency and the equivalent capacitance value, which effectively solves the phase correction problem of harmonic power measurement.

Synthesis and anti-HIV activity of non-nucleoside reverse-transcriptase inhibitor DB02 phosphate derivatives based on water-soluble optimization.

To improve the water solubility of anti-human immunodeficiency virus (HIV) agent DB02, an excellent non-nucleoside reverse-transcriptase inhibitor (NNRTI) obtained in our previous efforts, we designed and synthesized four phosphate derivatives of DB02 based on the molecular model of DB02 with RT. Here, the antiviral activity of these four derivatives was detected, leading to the discovery of compound P-2, which possessed a superior potency to the lead compound DB02 against wild-type HIV-1 and a variety of HIV-resistant mutant viruses significantly. Furthermore, the water solubility of P-2 was nearly 17 times higher than that of DB02, and the pharmacokinetic test in rats showed that P-2 demonstrate significantly improved oral bioavailablity of 14.6%. Our study showed that the introduction of a phosphate ester group at the end of the C-2 side chain of DB02 was beneficial to the improvement of its antiviral activity and pharmacokinetic properties, which provided a promising lead for the further development of S-DACOs type of NNRTIs.

Enhancing Third-Order Nonlinear Optical Property by Regulating Interaction between Zr4(embonate)6 Cage and N, N-Chelated Transition-Metal Cation.

Herein, the combination of anionic Zr4L6 (L = embonate) cages and N, N-chelated transition-metal cations leads to a series of new cage-based architectures, including ion pair structures (PTC-355 and PTC-356), dimer (PTC-357), and 3D frameworks (PTC-358 and PTC-359). Structural analyses show that PTC-358 exhibits a 2-fold interpenetrating framework with a 3,4-connected topology, and PTC-359 shows a 2-fold interpenetrating framework with a 4-connected dia network. Both PTC-358 and PTC-359 can be stable in air and other common solvents at room temperature. The investigations of third-order nonlinear optical (NLO) properties indicate that these materials show different degrees of optical limiting effects. It is surprising that increasing coordination interactions between anion and cation moieties can effectively enhance their third-order NLO properties, which can be attributed to the formation of coordination bonds that facilitate charge transfer. In addition, the phase purity, UV-vis spectra, and photocurrent properties of these materials were also studied. This work provides new ideas for the construction of third-order NLO materials.

Post-Assembly Modification of Homochiral Titanium-Organic Cages for Recognition and Separation of Molecular Isomers.

A chiral metal-organic cage (MOC) was extended and fixed into a porous framework using a post-assembly modification strategy, which made it easier to study the host-guest chemistry of the solid-state MOC using a single-crystal diffraction technique. Anionic Ti4 L6 (L=embonate) cage can be used as a 4-connecting crystal engineering tecton, and its optical resolution was achieved, thus homochiral ΔΔΔΔ- and ΛΛΛΛ-[Ti4 L6 ] cages were obtained. Accordingly, a pair of homochiral cage-based microporous frameworks (PTC-236(Δ) and PTC-236(Λ)) were easily prepared by a post-assembly reaction. PTC-236 has rich recognition sites provided by the Ti4 L6 moieties, chiral channels and high framework stability, affording a single-crystal-to-single-crystal transformation for guest structure analyses. Thus it was successfully utilized for the recognition and separation of isomeric molecules. This study provides a new approach for the orderly combination of well-defined MOCs into functional porous frameworks.

Probiotics Improve Postoperative Adaptive Immunity in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

There is no consensus on the effect of the probiotics on postoperative adaptive immunity in patients undergoing surgical resection for CRC. We aimed to systematically evaluate the effect of probiotics on postoperative adaptive immunity in perioperative CRC patients. The main end points were postoperative serum IgG, IgA, IgM, CD4+ T-cells, CD8+ T-cells and CD4+-to-CD8+ ratio. Meta-analysis was performed with a fixed or random effects model. We included six randomized controlled trials (RCTs) with 492 perioperative CRC patients. The use of enteral probiotics significantly increased the levels of peripheral blood IgG (MD: 1.33; 95% CI: 0.88 - 1.77; I2 = 41%), IgA (MD: 0.20; 95% CI: 0.10 - 0.30; I2 = 53%), IgM (MD: 0.18; 95% CI: 0.13 - 0.24; I2 = 41%), CD4+ T-cells (MD: 2.79; 95% CI: 2.34 - 3.24; I2 = 0) and CD4+-to-CD8+ ratio (MD: 0.09; 95% CI: 0.04 - 0.13; I2 = 7%). In conclusion, we report that the use of enteral probiotics improves postoperative humoral and cellular immunity in patients with CRC.

C6-structural optimizations of 2-aryl-1H-pyrazole-S-DABOs: From anti-HIV to anti-DENV activity.

Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC50 values in the range of 0.0508 âˆ¼ 0.0966 µM, and their selectivity index was SI > 1415 âˆ¼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC50 of compound 4a and 4b against DENV-II (13.2 µM and 9.23 µM, respectively) were better than that of the positive control ribavirin (EC50 = 40.78 µM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.

Ultrafast Excited-State Dynamics of Thiazole Orange.

Thiazole orange (TO), an asymmetric cyanine dye, has been widely used in biomolecular detection and imaging of DNA/ RNA in gels, due to its unique fluorogenic behavior: fluorescence of free dye in aqueous solution is very weak but emission can be significantly enhanced in nucleic-acid-bound dye. Herein we describe the ultrafast excited-state dynamics of free TO in aqueous solution by exploiting both a femtosecond upconversion spectrophotofluorometer and a picosecond time-correlated single-photon counting (TCSPC) apparatus. For the first time, the fluorescence lifetime of TO monomer in water was found to be ∼1 ps, mixed with concurrent solvent relaxation (which was confirmed by the experimental results of TO in DMSO). Even at moderate concentration, this lifetime has an amplitude (a measure of molecular fraction) that significantly dominates other lifetimes, and this is the origin of weak steady state fluorescence of free TO in water. We also found a novel slower decay component around 34 ps. Interestingly and in addition, the lifetime component on the 30-40 ps timescale was also found in TO-γ-Cyclodextrin (CD) complexes. The fraction of this component increased with the addition of γ-CD. Cyclodextrin has been reported to promote the aggregation of TO. Thus, although a very coincidental match of this time constant by one for a torsional process within the cavity can not be ruled out, we ascribe the shared 30-40 ps component to the lifetime of a highly quenched TO dimer experiencing intra-and inter-molecular rearrangement.

Phase-Separated Multienzyme Compartmentalization for Terpene Biosynthesis in a Prokaryote.

Liquid-liquid phase separation (LLPS) forms biomolecular condensates or coacervates in cells. Metabolic enzymes can form phase-separated subcellular compartments that enrich enzymes, cofactors, and substrates. Herein, we report the construction of synthetic multienzyme condensates that catalyze the biosynthesis of a terpene, α-farnesene, in the prokaryote E. coli. RGGRGG derived from LAF-1 was used as the scaffold protein to form the condensates by LLPS. Multienzyme condensates were then formed by assembling two enzymes Idi and IspA through an RIAD/RIDD interaction. Multienzyme condensates constructed inside E. coli cells compartmentalized the cytosolic space into regions of high and low enzyme density and led to a significant enhancement of α-farnesene production. This work demonstrates LLPS-driven compartmentalization of the cytosolic space of prokaryotic cells, condensation of a biosynthetic pathway, and enhancement of the biosynthesis of α-farnesene.

Clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Coordination Assembly of Tetrahedral Zr4(embonate)6 Cages with Eu3+ Ions.

Herein we systematically investigated the coordination assembly behavior of Zr4L6 cages with Eu3+ ions at room temperature. Through adjustment of the concentration of Eu salt and changes of the type and molar ratio of the solvent, a series of Zr4L6-Eu structures with different structure dimensionalities have been synthesized and structurally characterized. In addition, we also studied the optical properties of these materials in detail, including the fluorescent and third-order nonlinear-optical properties. Most notably, a 2D layer structure with a strong aromatic π···π-stacking force exhibits a good optical-limiting effect.

Combining a Titanium-Organic Cage and a Hydrogen-Bonded Organic Cage for Highly Effective Third-Order Nonlinear Optics.

Many metal-organic cages (MOCs) and a few hydrogen-bonded organic cages (HOCs) have been investigated, but little is reported about cooperative self-assembly of MOCs and HOCs. Herein, we describe an unprecedented MOC&HOC co-crystal composed of tetrahedral Ti4 L6 (L=embonate) cages and in-situ-generated [(NH3 )4 (TIPA)4 ] (TIPA=tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine) cages. Chiral transfer is observed from the enantiopure Ti4 L6 cage to enantiopure [(NH3 )4 (TIPA)4 ] cage. Two homochiral supramolecular frameworks with opposite handedness (PTC-235(Δ) and PTC-235(Λ)) are formed. Such MOC&HOC co-crystal features high stability in water and other solvents, affording single-crystal-to-single-crystal transformation to trap CH3 CN molecules and identify disordered NH4 + cations. A tablet pressing method is developed to test the third-order nonlinear optical property of KBr-based PTC-235 thin film. Such a thin film exhibits an excellent optical limiting effect.

Ti4(embonate)6 Cage-Ligand Strategy on the Construction of Metal-Organic Frameworks with High Stability and Gas Sorption Properties.

Herein we report an efficient strategy to construct cage-based metal-organic frameworks (MOFs) via the assembly of Ti4L6 (L = embonate) cages and N-contained ligands with Mn2+ and Zn2+ ions, respectively, and two Ti4L6-cage-based MOFs (PTC-219 and PTC-220) with high stability and gas sorption properties have been generated through two-step reactions, respectively.