Taxodin A, a Cytotoxic C30 Terpenoid from Taxodium mucronatum with a Unique Skeleton.

Taxodin A (1), a unique C30 terpenoid featuring an unprecedented skeleton composed of an abietane-type diterpene and a menthane-type monoterpene, was obtained from the leaves and branches of Taxodium mucronatum. The structure and absolute configuration of compound 1 was unequivocally established by the combination of extensive spectroscopic analyses and X-ray single-crystal diffraction analysis. Compound 1 exhibited potent cytotoxic activities against A549, SMMC-7721, MDA-MB-231, and SW480 cell lines with IC50 values of 15.35±0.73, 8.49±0.35, 17.53±0.79, 18.93±0.60 µM, respectively.

Femoral Neck System vs. four cannulated screws in the treatment of Pauwels III femoral neck fracture.

OBJECTIVE: To compare the clinical efficacy of the Femoral Neck System (FNS) vs. four cannulated screws in Pauwels III femoral neck fractures. METHODS: This retrospective study included patients with newly occurred type Pauwels III femoral neck fracture treated at author' Hospital of between January 2017 and February 2021. The patients received FNS (n = 27) or four cannulated screws (control group, n = 31). The operation time, blood loss, fracture healing time, incidence of complications (such as short femoral neck, necrosis of femoral head, nonunion of fracture, and failure of internal fixation withdrawal), and hip Harris score at the last follow-up were analyzed. RESULTS: The operation time, blood loss, and fracture healing time were not significantly different between the two groups (all P > 0.05). In the FNS group, three and one patients were with femoral neck shortening and femoral head necrosis, respectively, while no fracture nonunion or failure of internal fixation withdrawal occurred. In the control group, seven, two, one, and two patients were with femoral neck shortening, femoral head necrosis, nonunion, and internal fixation failure, respectively. The cumulative complication incidence was 14.8% and 38.7% in the FNS and control groups (P = 0.042). The excellent and good rates of the hip Harris score at the last follow-up were 92.6% and 71.0% in the FNS and control groups, respectively (P = 0.036). CONCLUSION: The study suggested that the clinical efficacy of FNS was better than internal fixation using four cannulated screws in treating Pauwels III type femoral neck fracture.

Studying the effects of carbon nanotube contents on stretch-induced crystallization behavior of polyethylene/carbon nanotube nanocomposites using molecular dynamics simulations.

In the present work, we used molecular dynamics simulations to study the effects of carbon nanotube (CNT) contents on stretch-induced crystallization behavior in CNT filled polyethylene systems. During high-temperature stretching, the stretching is responsible for the orientation of CNTs, which then facilitates segment orientation and conformational transition from the gauche-conformation into the trans-conformation in interfacial regions. The systems with higher CNT contents have a higher degree of orientation and higher contents of trans-conformation during stretching, resulting in the formation of more precursors. During subsequent crystallization, the initial crystallization rate increases with the increase of the CNT content due to the increase in precursor contents in interfacial regions. However, after the CNT content exceeds a certain value, a filler network would be formed by CNTs, which can restrict chain movements and then lead to a decrease in the overall crystallization rate in the systems with high CNT contents.

Vibsane-Type Diterpenoids: Structures, Derivatives, Bioactivities, and Synthesis.

Vibsane-type diterpenoids isolated from the genus Viburnum, are rare 6-11 membered ring polysubstituted macrocyclic diterpenoids. Since the first report of vibsane-type diterpenoids from V. odoratissimum in 1980, they have attracted the attention of scientists due to their complex structures, excellent biological activities, and great synthetic challenges. Recently, there are some notable research achievements on the discovery, synthesis, structural modification, and pharmacological mechanism of vibsane-type diterpenoids. Therefore, we will focus on these aspects to review important achievements of vibsane diterpenoids between 1980-2021.

Design and fabrication of a sensitive electrochemical sensor for uranyl ion monitoring in natural waters based on poly (brilliant cresyl blue).

New insights are proposed into enhancing detection of uranyl ions (UO22+) by electropolymerization brilliant cresyl blue-modified glassy carbon electrode (PBCB/GCE). The mercury-free PBCB/GCE sensor was applied to determine UO22+ in water samples by differential pulse adsorptive stripping voltammetry (DPAdSV). The unique combination of the PBCB/GCE and DPAdSV significantly improves sensitivity due to the polymer of high electroactive area and fast electron transfer rate. The DPAdSV current using a 3 mm diameter PBCB/GCE was proportional to the UO22+ concentration in the range 2.0-90.0 µg·L-1 (- 0.113 V vs. SCE) with a detection limit of 0.650 µg·L-1, RSD = 3.1% (n = 10), and 4.5% reproducibility. In addition, the sensitivity for UO22+ determination was further improved at using an 1 mm diameter PBCB/GCE, which enhances the efficiency of UO22+ deposition due to its higher current density. The 1 mm diameter PBCB/GCE based on DPAdSV technique could be used to determine uranyl ions in the concentration range 0.20-2.0 µg·L-1 (- 0.113 V vs. SCE) with a detection limit of 0.067 µg·L-1, RSD = 5.7 % (n = 10) and 5.4% reproducibility. Hence, the PBCB/GCE is a suitable candidate to substitute the mercury electrode. Graphical abstract.

Multilevel Chirality Transfer from Amino Acid Derivatives to Circularly Polarized Luminescence-Active Nanoparticles in Aqueous Medium.

Chirality at different levels is widely observed in nature, but the clue to connect it all together, and the way chirality transfers among different levels are still obscure. Herein, a l-/d-lysine-based self-assembly system was constructed, in which two-step chirality transfer among three different levels was observed in aqueous solution. The chirality originated from the point chirality of amino acid derivatives l-/d-PyLys hydrochloride, and was transferred to the planar conformational chirality of water-soluble pillar[5]arene pR-/pS-WP5. Then, with the aid of pR-/pS-WP5, nanoparticles were formed that exhibited L-/R-handed circularly polarized luminescence with a dissymmetry factor of up to ±0.001, arising from pyrene chiral excimers. This multilevel chirality transfer not only provides a perspective to trace potential clues, and to pursue certain ways by which the chirality transfers, but also offers a strategy to create controllable CPL emission in aqueous media.

Molecular simulation of polymer crystallization under chain and space confinement.

Polymer crystallization under chain and space confinements is studied by Monte Carlo simulation. The simulation results show that the crystallinity and melting temperature of confined systems increase with the increase of free chain content. Furthermore, the crystallinity and melting temperature of confined systems with larger lateral size are higher than those with smaller lateral size. These findings are in good agreement with the conclusions obtained in some experiments. An important phenomenon that cannot be observed in experiments has been confirmed, that is, the tethering point can be used as the nucleation site. For the confined polymer system with the lateral size of 8 lattice points, with the increase of free chain content, the surface free energy of the nuclei and the diffusion activation energy of the chains decrease due to the combined effects of chain conformation size and chain movement ability, which leads to the enhancement of the nucleation ability of polymers. However, for the confined polymer system with lateral size of 12 lattice points, with the increase of free chain content, the nucleation sites decrease and the critical free energy barrier increases, which are not conducive to nucleation. Moreover, the existence of interfacial interactions can also significantly change the crystallization of confined polymers. Our results indicate the crystallization kinetics of the confined polymer from a microscopic point of view.

Three-Dimensional Finite Element Analysis and Biomechanical Analysis of Midfoot von Mises Stress Levels in Flatfoot, Clubfoot, and Lisfranc Joint Injury.

BACKGROUND Midfoot deformity and injury can affect the internal pressure distribution of the foot. This study aimed to use 3D finite element and biomechanical analyses of midfoot von Mises stress levels in flatfoot, clubfoot, and Lisfranc joint injury. MATERIAL AND METHODS Normal feet, flatfeet, clubfeet (30 individuals each), and Lisfranc injuries (50 individuals) were reconstructed by CT, and 3D finite element models were established by ABAQUS. Spring element was used to simulate the plantar fascia and ligaments and set hyperelastic coefficients in encapsulated bone and ligaments. The stance phase was simulated by applying 350 N on the top of the talus. The von Mises stress of the feet and ankle was visualized and analyzed. RESULTS The von Mises stress on healthy feet was higher in the lateral metatarsal and ankle bones than in the medial metatarsal bone. Among the flatfoot group, the stress on the metatarsals, talus, and navicular bones was significantly increased compared with that on healthy feet. Among patients with clubfeet, stress was mainly concentrated on the talus, and stress on the lateral metatarsal and navicular bones was significantly lower. The von Mises stress on the fractured bone was decreased, and the stress on the bone adjacent to the fractured bone was higher in Lisfranc injury. During bone dislocation alone or fracture accompanied by dislocation, the von Mises stress of the dislocated bone tended to be constant or increased. CONCLUSIONS Prediction of von Mises stress distribution may be used clinically to evaluate the effects of deformity and injury on changes in structure and internal pressure distribution on the midfoot.

Monoterpene Indole Alkaloids with Cav3.1 T-Type Calcium Channel Inhibitory Activity from Catharanthus roseus.

Catharanthus roseus is a well-known traditional herbal medicine for the treatment of cancer, hypertension, scald, and sore in China. Phytochemical investigation on the twigs and leaves of this species led to the isolation of two new monoterpene indole alkaloids, catharanosines A (1) and B (2), and six known analogues (3-8). Structures of 1 and 2 were established by 1H-, 13C- and 2D-NMR, and HREIMS data. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction analysis. Compound 2 represented an unprecedented aspidosperma-type alkaloid with a 2-piperidinyl moiety at C-10. Compounds 6-8 exhibited remarkable Cav3.1 low voltage-gated calcium channel (LVGCC) inhibitory activity with IC50 values of 11.83 ± 1.02, 14.3 ± 1.20, and 14.54 ± 0.99 µM, respectively.

Ultra-compact hybrid plasmonic mode convertor based on unidirectional eigenmode expansion.

An ultra-compact hybrid plasmonic mode convertor is demonstrated based on a hybrid plasmonic slot waveguide structure. Benefiting from the unidirectional eigenmode expansion approach, a mode-interference-based ${{\rm TE}_{00}}$TE00-to-${{\rm TM}_{01}}$TM01 mode convertor is realized for the first time, to the best of our knowledge, with an ultra-compact footprint of only ${2}.{33} \times {7}\,\,\unicode{x00B5} {{\rm m}^2}$2.33×7µm2. At the wavelength of 1550 nm, the insertion loss is below 2.34 dB, and the extinction ratio is 25.6 dB with mode conversion purity as high as 94.6%. The extinction ratio is over 15.5 dB for the entire C-band with a bandwidth of extinction ratio above 10 dB larger than 110 nm. The transmissivity of the crosstalk ${{\rm TE}_{10}}$TE10 and ${{\rm TE}_{02}}$TE02 at 1550 nm is $ - {16.1}$-16.1 and $ - {22.7}\,\,{\rm dB}$-22.7dB, respectively.

Demonstration of a robust insertion loss measuring approach for low-loss silicon photonic devices.

A robust optical insertion loss measuring approach based on a symmetrically coupled add-drop microring resonator is demonstrated on silicon-on-insulator platform. Utilizing resonant wavelengths and relative values of measured optical power, this approach frees the insertion loss measurement from the uncertainties caused by experimental set-up, including system alignment and wavelength dependence of the couplers. Strip-slot mode converters were fabricated and measured to present the exemplary insertion loss measurement process. A series of experimental results confirm that the insertion loss of the low-loss silicon photonic devices can be accurately and reliably obtained even the adopted couplers are wavelength-dependent, and the fibers are deviated 15 µm from the horizontal direction and 110 µm from the vertical direction, exhibiting excellent robustness to the experimental set-up.

pDHS-DSET: Prediction of DNase I hypersensitive sites in plant genome using DS evidence theory.

Predicting DNase I hypersensitive sites (DHSs) is an essential topic in the field of transcriptional regulatory elements, which provides clues for deciphering the function of noncoding genomic regions. To the best of our knowledge, several computational approaches are currently available for prediction of DHSs in the plant genome, but there is still room for improvement. In the present work, a DS evidence theory-based method was proposed. At first, four sequence-derived feature representation methods, i.e., kmer, reverse complement kmers, mismatch profile, and pseudo dinucleotide composition, were utilized to encode the sequences. Then, four support vector machine based sub-classifiers was built with these sequence-derived features. Finally, the DS evidence theory was applied to obtain the final results by fusing the outputs of these four base learners. In this work, to solve the data imbalance problem, a bidirectional synthetic sampling algorithm was proposed to obtain balanced dataset during training the models. In the computational experiments, the proposed method achieved accuracy up to 88.85%, and 88.60% in Arabidopsis thaliana and rice genome, respectively. Compared with existing DHSs prediction methods, the proposed method can achieve comparable or better performances, suggesting the usefulness of the method for DHSs prediction.

Stereocomplex formation in mixed polymers filled with two-dimensional nanofillers.

The presence of nanofillers, such as graphene, can effectively promote stereocomplex formation in poly(l-lactide)/poly(d-lactide) blends. However, the detailed microscopic mechanism of the improved formation of stereocomplex crystallites (SCs) in filled polylactides is still unclear. Therefore, we performed dynamic Monte Carlo simulations to reveal the underlying mechanism of the effect of two-dimensional nanofillers on the formation of SCs in polymer blends. It was observed that the nanofillers can lead to the occurrence of heterogeneous nucleation of mixed polymer chains. On one hand, the miscibility of mixed polymers is improved in the interfacial regions, attributed to attractive interactions between polymers and nanofillers. On the other hand, for the heterogeneous nucleation process, chains prefer to crystallize by means of intermolecular packing alignment. Both phenomena contribute to the promotion of SCs.

Monte Carlo simulations of stereocomplex formation in multiblock copolymers.

Currently, controlling the formation of stereocomplex crystallites (SCs) in enantiomeric PLA blends is a research hotspot. In the present work, we performed dynamic Monte Carlo simulations to study the formation mechanism of SCs in multiblock copolymers. The effects of block number and crystallization temperature on SC formation were revealed. The relative size of block length and crystal thickness is an important factor. In the multiblock copolymers with block length longer than crystal thickness, both the increases of crystallization temperature and block number lead to the increase of SC content attributed to the relatively high degree of supercooling for SC formation and the improved local miscibility between different blocks, respectively. In the multiblock copolymers with block length equal to crystal thickness, each block can just form one crystalline stem, and then different blocks can be more easily alternately parallel-packed during SC formation. The system thus reaches the upper limit of the ability to form SCs. Therefore, both the further increases in crystallization temperature and block number can no longer cause the enhancement in SC formation.

Fluorometric determination of sulfadiazine by using molecularly imprinted poly(methyl methacrylate) nanobeads doped with manganese(II)-doped ZnS quantum dots.

The surface of poly(methyl methacrylate) nanospheres (PMMA-NSs) was molecularly imprinted with sulfadiazine by a surface imprinting method. Simultaneously, Mn(II)-doped ZnS quantum dots were incorporated into the imprinted PMMA-NSs. The morphology of the fluorescent nanoprobe was characterized by transmission electron microscopy which revealed good spheroidal core-shell structure and a homogeneous distribution of the QDs. Following binding of sulfadiazine, fluorescence (best measured at excitation/emission maxima of 335/592 nm) is increasingly quenched. The detection range is 5-40 µmol·L-1 of sulfadiazine, and the detection limit is 0.24 µmol·L-1. The fluorescence quenching mechanism is discussed, and a photo-induced electron transfer process is shown to account for quenching. The fluorescent probe was applied to the determination of sulfadiazine in spiked tap water with recoveries and RSDs of 96.6-100.2% and 2.7-3.9%, respectively. The detection of sulfadiazine in spiked lake water exhibited the recoveries and RSDs with 99.3-104.8% and 1.8-4.2%, respectively. Graphical abstract Schematic presentation of synthesis of PMMA-Ns, Mn-doped ZnS QDs, MQPs, and the elution diagram of SD from MQPs, and the relative reagents including: sodium dodecyl benzene sulfonate(SDBS), (3-aminopropyl)triethoxysilane(APTES), 3-mercaptopropionic acid (MPA), tetraethylorthosilicate(TEOS)and sulfadiazine(SD), and nanoparticles including: polymer(methyl methacrylate) nanospheres(PMMANs), MIPs@QDs@PMMANs(MQPs) and carbon quantum dots(CQDs).

Convection-enhanced delivery for diffuse intrinsic pontine glioma: a single-centre, dose-escalation, phase 1 trial.

BACKGROUND: Diffuse intrinsic pontine glioma is one of the deadliest central nervous system tumours of childhood, with a median overall survival of less than 12 months. Convection-enhanced delivery has been proposed as a means to efficiently deliver therapeutic agents directly into the brainstem while minimising systemic exposure and associated toxic effects. We did this study to evaluate the safety of convection-enhanced delivery of a radioimmunotherapy agent targeting the glioma-associated B7-H3 antigen in children with diffuse intrinsic pontine glioma. METHODS: We did a phase 1, single-arm, single-centre, dose-escalation study at the Memorial Sloan Kettering Cancer Center (New York, NY, USA). Eligible patients were aged 3-21 years and had diffuse intrinsic pontine glioma as diagnosed by consensus of a multidisciplinary paediatric neuro-oncology team; a Lansky (patients <16 years of age) or Karnofsky (patients ≥16 years) performance score of at least 50 at study entry; a minimum weight of 8 kg; and had completed external beam radiation therapy (54·0-59·4 Gy at 1·8 Gy per fraction over 30-33 fractions) at least 4 weeks but no more than 14 weeks before enrolment. Seven dose-escalation cohorts were planned based on standard 3 + 3 rules: patients received a single infusion of 9·25, 18·5, 27·75, 37, 92·5, 120·25, or 148 MBq, respectively, at a concentration of about 37 MBq/mL by convection-enhanced delivery of the radiolabelled antibody [124I]-8H9. The primary endpoint was identification of the maximum tolerated dose. The analysis of the primary endpoint was done in the per-protocol population (patients who received the full planned dose of treatment), and all patients who received any dose of study treatment were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01502917, and is ongoing with an expanded cohort. FINDINGS: From April 5, 2012, to Oct 8, 2016, 28 children were enrolled and treated in the trial, of whom 25 were evaluable for the primary endpoint. The maximum tolerated dose was not reached as no dose-limiting toxicities were observed. One (4%) of 28 patients had treatment-related transient grade 3 hemiparesis and one (4%) had grade 3 skin infection. No treatment-related grade 4 adverse events or deaths occurred. Estimated volumes of distribution (Vd) were linearly dependent on volumes of infusion (Vi) and ranged from 1·5 to 20·1 cm3, with a mean Vd/Vi ratio of 3·4 (SD 1·2). The mean lesion absorbed dose was 0·39 Gy/MBq 124I (SD 0·20). Systemic exposure was negligible, with an average lesion-to-whole body ratio of radiation absorbed dose higher than 1200. INTERPRETATION: Convection-enhanced delivery in the brainstem of children with diffuse intrinsic pontine glioma who have previously received radiation therapy seems to be a rational and safe therapeutic strategy. PET-based dosimetry of the radiolabelled antibody [124I]-8H9 validated the principle of using convection-enhanced delivery in the brain to achieve high intra-lesional dosing with negligible systemic exposure. This therapeutic strategy warrants further development for children with diffuse intrinsic pontine glioma. FUNDING: National Institutes of Health, The Dana Foundation, The Cure Starts Now, Solving Kids' Cancer, The Lyla Nsouli Foundation, Cookies for Kids' Cancer, The Cristian Rivera Foundation, Battle for a Cure, Cole Foundation, Meryl & Charles Witmer Charitable Foundation, Tuesdays with Mitch Charitable Foundation, and Memorial Sloan Kettering Cancer Center.

pDHS-ELM: computational predictor for plant DNase I hypersensitive sites based on extreme learning machines.

DNase I hypersensitive sites (DHSs) are hallmarks of chromatin zones containing transcriptional regulatory elements, making them critical in understanding the regulatory mechanisms of gene expression. Although large amounts of DHSs in the plant genome have been identified by high-throughput techniques, current DHSs obtained from experimental methods cover only a fraction of plant species and cell processes. Furthermore, these experimental methods are both time-consuming and expensive. Hence, it is urgent to develop automated computational means to efficiently and accurately predict DHSs in the plant genome. Recently, several methods have been proposed to predict the DHSs. However, all these methods took a lot of time to build the model, making them inappropriate for data with massive volume. In the present work, a new ensemble extreme learning machine (ELM)-based model called pDHS-ELM was proposed to predict the DHSs in the plant genome by fusing two different modes of pseudo-nucleotide composition. Here, two kinds of features including reverse complement kmer and pseudo-nucleotide composition were used to represent the DHSs. The ELM model was used to build the base classifiers. Then, an ensemble framework was employed to combine the outputs of these base classifiers. When applied to DHSs in Arabidopsis thaliana and rice (Oryza sativa) genome, the proposed method could obtain accuracies up to 88.48 and 87.58%, respectively. Compared with the state-of-the-art techniques, pDHS-ELM achieved higher sensitivity, specificity, and Matthew's correlation coefficient with much less training and test time. By employing pDHS-ELM, we identified 42,370 and 103,979 DHSs in A. thaliana and rice genome, respectively. The predicted DHSs were depleted of bulk nucleosomes and were tightly associated with transcription factors. Approximately 90% of the predicted DHSs were overlapped with transcription factors. Meanwhile, we demonstrated that the predicted DHSs were also associated with DNA methylation, nucleosome positioning/occupancy, and histone modification. This result suggests that pDHS-ELM can be considered as a new promising and powerful tool for transcriptional regulatory elements analysis. Our pDHS-ELM tool is available from the following website https://github.com/shanxinzhang/pDHS-ELM/ .

High-gain erbium silicate waveguide amplifier and a low-threshold, high-efficiency laser.

Erbium-doped materials have played an important role in the fabrication of light sources used in silicon photonics. Recent studies demonstrated that erbium silicate nanowire had a high net gain attributable to its high erbium concentration and excellent material quality. We establish a more accurate and comprehensive theoretical model of erbium silicate nanowire, analyze the modeled nanowire's properties, and optimize a high-gain erbium silicate waveguide amplifier and low-threshold, high-efficiency laser by considering upconversion, energy transfer, and amplified spontaneous emission. The simulation results and previous experimental data reported in reference showed some agreement. A proposed waveguide amplifier, based on the optimized design, displayed a gain greater than 20 dB/mm. Then, a 3.3 mW low-threshold laser with a maximum power-conversion efficiency of 50% was modeled by choosing the optimized resonator cavity and reflector. The results indicate that erbium silicate compound materials with large optical gains can serve as potential candidates for inclusion in scale-integrated amplifiers and other applications requiring lasers.

Universal isocontours for dissipative Kerr solitons.

Dissipative Kerr solitons can be generated within an existence region defined on a space of normalized pumping power versus cavity-pump detuning frequency. The contours of constant soliton power and constant pulse width in this region are studied through measurement and simulation. Such isocontours impart structure to the existence region and improve understanding of soliton locking and stabilization methods. As part of the study, dimensionless, closed-form expressions for soliton power and pulse width are developed (including Raman contributions). They provide isocontours in close agreement with those from the full simulation, and, as universal expressions, can simplify the estimation of soliton properties across a wide range of systems.

Ratiometric fluorescence nanosensors based on core-shell structured carbon/CdTe quantum dots and surface molecularly imprinted polymers for the detection of sulfadiazine.

Sulfadiazine is an environmental pollutant derived from abuse of antibiotics. Its content in environmental water is closely related to human health. Thus, a novel dual-emission surface molecularly imprinted nanosensor is designed for the specific adsorption and detection of sulfadiazine. In the system, blue emissive carbon quantum dots wrapped with silica served as the internal reference signal for eliminating background interference, while red emissive thioglycolic acid modified CdTe quantum dots (CdTe QDs), which are low dimensional semiconductor materials by the combination of cadmium and tellurium with excellent optical properties, were encapsulated in the imprinted layer to offer recognition signal. The fluorescence of CdTe quantum dots was quenched and the fluorescence quenching degree of carbon quantum dots was inconspicuous with the increase of concentration of sulfadiazine, thereby reflecting the color change. The detection of sulfadiazine was successfully achieved in a concentration range of 0.25-20 µmol/L with detection limit of 0.042 µmol/L and nanosensors had specific recognition for sulfadiazine over its analogues. Compared to single-emission fluorescence sensors, ratiometric fluorescence nanosensors had wider linear range and higher detection accuracy. Furthermore, the nanosensors were also successfully applied for the determination of sulfadiazine in real water and milk samples with acceptable recoveries. The study provides a feasible method for the detection of sulfadiazine and a reference for the detection of sulfonamides.