[Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis].

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

The complementary and alternative roles of elemene injection in cancer: An umbrella review.

BACKGROUND: In the past, many meta-analyses (MAs) suggested that elemene injection (EI) played a complementary and alternative role in cancer treatment. However, some results were contradictory and a lot of evidences weren't classified. Thus, their clinical guidance effect was very limited. METHODS: Two reviewers independently retrieved 8 databases from their origin to May 19, 2023 and appropriate MAs were taken into consideration. A pooled analysis was conducted to merge results extracted from trials of included MAs. The methodological quality of MAs and the evidence certainty of pooled results were assessed. RESULTS: 31 MAs were taken into analysis with poor methodological quality. The main weaknesses were in the areas of heterogeneity analysis, bias risk, and literature selection. According to the present evidence, on the one hand, compared with conventional treatment (CT) alone, EI combined with CT may significantly enhance short-term or long-term efficacy and reduce adverse reactions caused by CT in multiple cancers. On the other hand, using EI alone also can improve ORR in the malignant (pleural) effusion and lessen the recurrence rate in bladder cancer obviously with fewer adverse reactions compared with CT alone. However, this evidence was rated as moderate to very low certainty mainly due to the risk of bias in clinical trials. CONCLUSION: EI may be a viable medication for the treatment of cancer although more convincing trials are still required to demonstrate its alternative and complementary benefits. Besides, it seems to have a broad potential for further development in immunotherapy, drug delivery technique, and predictive factor.

In Situ Ellipsometry Measurements on the Halide Phase Segregation of Mixed Halide Lead Perovskites.

Methylammonium lead iodide bromides MAPb(Brx I1-x )3 are a class of mixed halide lead perovskites, materials that offer high-power conversion efficiencies and bandgap tunability. For these reasons, they are a promising absorber material for future solar cells, although their use is still limited due to several factors. The reversible phase segregation under even low light intensities is one of them, lowering the effective bandgap due to local segregation into iodide-rich and bromide-rich phases. While several studies have been done to illuminate the mechanism and suppression of phase segregation, challenges remain to understand its kinetics. We obtained dynamic ellipsometric measurements from x=0.5 mixed halide lead perovskite thin films protected by a polystyrene layer under green laser light with a power density of ∼11 W/cm2 . Time constants between 1.7(±0.7)×10-3  s-1 for the segregation and 1.5(±0.6)×10-4  s-1 for recovery were calculated. The phase segregation rate constants are surprisingly two orders of magnitude slower than and the recovery rate is consistent with those measured using photoluminescence methods under similar conditions. These results confirm a concern in the literature about the complexity in the phase separation kinetics measured from photoluminescence. We expect ellipsometry to serve as a complementary technique to other spectroscopies in studying mixed-halide lead perovskites phase segregation in the future.

Phenotypic plasticity and exotic plant invasions: Effects of soil nutrients, species nutrient requirements, and types of traits.

High-phenotypic plasticity has long been considered as a characteristic promoting exotic plant invasions. However, the results of the studies testing this hypothesis are still inconsistent. Overlooking the effects of species resource requirements and environmental resource availability may be the main reasons for the ambiguous conclusions. Here, we compared phenotypic plasticity between five noxious invasive species with different nutrient requirements (evaluated using the soil nutrient status of their natural distribution ranges) and their phylogenetically related natives under five nutrient levels. We found that species with high-nutrient requirements showed greater plasticity of total biomass than species with low-nutrient requirements, regardless of their status (invasive or native). Invasives with high-nutrient requirements had greater growth plasticity than their related natives, which may contribute to their invasiveness under high-nutrient environments. However, compared with the related natives, a higher growth plasticity may not help exotic species with low-nutrient requirements to invade nutrient-rich habitats, and exotic species with high-nutrient requirements to invade nutrient-limited habitats. In contrast, invasives with low-nutrient requirements exhibited lower growth plasticity than their related natives, contributing to their invasiveness under nutrient-limited habitats. Functional traits showed growth-related plasticity in only 10 cases (3.8%), and there was no functional trait whose plastic response to soil nutrients was beneficial to exotic plant invasions. Our study indicates that low-growth plasticity could also promote exotic plant invasions, high plasticity may not necessarily lead to invasiveness. We must test the adaptive significance of plasticity of functional traits when studying its biological roles.

Why Should the Reaction Order of a Bimolecular Reaction be 2.33 Instead of 2?

Predicting the reaction kinetics, that is, how fast a reaction can happen in a solution, is essential information for many processes, such as industrial chemical manufacturing, refining, synthesis and separation of petroleum products, environmental processes in air and water, biological reactions in cells, biosensing, and drug delivery. Collision theory was originally developed to explain the reaction kinetics of gas reactions with no dilution. For a reaction in a diluted inert gas solution or a diluted liquid solution, diffusion often dominates the collision process. Thus, it is necessary to include diffusion in such a calculation. Traditionally, the classical Smoluchowski rate is used as a starting point to predict the collision frequency of two molecules in a diluted solution. In this report, a different collision model is derived from the adsorption of molecules on a flat surface. A surprising result is obtained, showing that the reaction order for bimolecular reactions should be 2 and 1/3 instead of 2, following a fractal reaction kinetics.

The spatiotemporal variations in microalgae communities in vertical waters of a subtropical reservoir.

The construction of cascade reservoirs increases eutrophication and exacerbates algal blooms and thus threatens water quality. Previous studies on the microalgae in reservoir have mainly focused on the spatio-temporal patterns of surface microalgae communities at the horizontal scale, while few studies have simultaneously considered the successions of microalgae in vertical profiles including the sediments and the effects of the nutrients release and microalgae in sediments on microalgae in upper waters. In this study, we investigated the effects of microalgae and physico-chemical parameters in waters and sediments on the successions of vertical microalgae communities in Xipi Reservoir, Southeast China. The seasonal variations in microalgae compositions decreased gradually from the surface water (the dominance of Cryptophyta and Chlorophyta in spring, Chlorophyta and Cyanophyta in summer, and relatively uniform in autumn and winter) to the sediment (the dominance of Bacillariophyta throughout the year), which was influenced by the variations of physico-chemical factors in different layers. The spatio-temporal variations in microalgae communities in waters was attributing to not only the heterogeneities of the stratification, and the physico-chemical factors such as water temperature, pH, and nutrient concentrations, especially for phosphorus in the water column, but also the combinations of phosphorus release and microalgae composition in sediments. Environmental changes would be especially problematic for microalgae groups such as Cryptophyta, Dinophyta and Chlorophyta that were sensitive to the changes of temperature and nutrients. Our results are helpful for an extensive understanding of the dynamics of microalgae communities in reservoir, and contribute to reservoir management for ensuring the safety of drinking water.

Teaching undergraduate physical chemistry lab with kinetic analysis of COVID-19 in the United States.

A physical chemistry lab for undergraduate students described in this report is about applying kinetic models to analyze the spread of COVID-19 in the United States and obtain the reproduction numbers. The susceptible-infectious-recovery (SIR) model and the SIR-vaccinated (SIRV) model are explained to the students and are used to analyze the COVID-19 spread data from U.S. Centers for Disease Control and Prevention (CDC). The basic reproduction number R 0 and the real-time reproduction number R t of COVID-19 are extracted by fitting the data with the models, which explains the spreading kinetics and provides a prediction of the spreading trend in a given state. The procedure outlined here shows the differences between the SIR model and the SIRV model. The SIRV model considers the effect of vaccination which helps explain the later stages of the ongoing pandemic. The predictive power of the models is also shown giving the students some certainty in the predictions they made for the following months.

Bag-of-features-based radiomics for differentiation of ocular adnexal lymphoma and idiopathic orbital inflammation from contrast-enhanced MRI.

OBJECTIVES: To evaluate the effectiveness of bag-of-features (BOF)-based radiomics for differentiating ocular adnexal lymphoma (OAL) and idiopathic orbital inflammation (IOI) from contrast-enhanced MRI (CE-MRI). METHODS: Fifty-six patients with pathologically confirmed IOI (28 patients) and OAL (28 patients) were randomly divided into training (n = 42) and testing (n = 14) groups. One hundred sixty texture features extracted from the CE-MR image were encoded into the BOF representation with fewer features. The support vector machine (SVM) with a linear kernel was used as the classifier. Data augmented was performed by cropping orbital lesions in different directions to alleviate the over-fitting problem. Student's t test and the Holm-Bonferroni method were employed to compare the performance of different analysis methods. The chi-square test was used to compare the analysis with MRI and human radiological diagnosis. RESULTS: In the independent testing group, the differentiation by the BOF features with augmentation achieved an area under the curve (AUC) of 0.803 (95% CI: 0.725-0.880), which was significantly higher than that of the BOF features without augmentation and that of the texture features (p < 0.05). In addition, the same radiomic analysis with pre-contrast MRI obtained an AUC of 0.618 (95% CI: 0.560-0.677), which was significantly lower than that with CE-MRI. The diagnostic performance of the analysis with CE-MRI was significantly better than the radiology resident (p < 0.05) but had no significant difference with the experienced radiologist, even though there was less consistency between the radiomic analysis and the human visual diagnosis. CONCLUSIONS: The BOF-based radiomics may be helpful for the differentiation between OAL and IOI. KEY POINTS: • It is challenging to differentiate OAL from IOI due to the similar clinical and image features. • Radiomics has great potential for the noninvasive diagnosis of orbital diseases. • The BOF representation from patch to image may help the differentiation of OAL and IOI.

Automated Determination of Dissolved Reactive Phosphorus at Nanomolar to Micromolar Levels in Natural Waters Using a Portable Flow Analyzer.

Automated in-field methods for measuring dissolved reactive phosphorus (DRP) over a large concentration range are in high demand for the purpose of better understanding the biogeochemistry of phosphorus in the river-estuary-coast continuum to the open ocean. Here, an automated portable and robust analyzer was described for the determination of nanomolar to micromolar levels of DRP in natural waters. The quantification of DRP was based on classic phosphomolybdenum blue (PMB) chemistry. All the components of the analyzer were computer-controlled using LabVIEW-based laboratory-programmed software. When equipped with a 3 cm Z-type flow cell, the system demonstrated linearity with concentrations up to 12 µmol L-1, a sampling rate of 20 h-1, a limit of detection of 0.11 µmol L-1, and relative standard deviations (RSDs) of 0.4-4.6% (n = 11-576). When a solid-phase extraction cartridge was combined with the analyzer, the PMB formed from the sample was automatically concentrated on the hydrophilic-lipophilic balanced sorbent. The concentrated PMB compound was eluted with NaOH solution and measured in the spectrophotometric system. Under optimal conditions, the nanomolar-level mode afforded a sampling rate of 8 h-1, a limit of detection of 1.7 nmol L-1, and RSDs of 3.0-5.7% (n = 11-120). The system exhibited advantages that included a wide linear range, high sensitivity and reproducibility, low reagent consumption, and insignificant interference from salinity, silicate, arsenate, and other P-containing compounds. The system was successfully applied for discrete sample analysis, fixed site online monitoring, and the real-time underway measurement of DRP in riverine-estuarine-coastal waters.

Time-resolved temperature-jump measurements and steady-state thermal imaging of nanoscale heat transfer of gold nanostructures on AlGaN:Er3+ thin films.

For a nanostructure sitting on top of an AlGaN:Er3+ thin film, a new thermal imaging technique is presented where dual cameras collect bandpass filtered videos from the H and S bands of Er3+ emission. We combine this thermal imaging technique with our newly developed time-resolved temperature measurement technique which relies on luminescence thermometry using Er3+ emission. This technique collects time-resolved traces from the H and S bands of Er3+ emission. The H and S signal traces are then used to reconstruct the time-resolved temperature transient when a nanostructure is illuminated with a pulsed 532 nm light. Two different types of samples are interrogated with these techniques (drop-casted gold nanosphere cluster and lithographically prepared gold nanodot) on the AlGaN:Er3+ film. Steady-state and time-resolved temperature data are collected when the samples are immersed in air and water. The results of time-resolved temperature-jump measurements from a cluster of gold nanospheres show extremely slow heat transfer when the cluster is immersed in water and nearly 200-fold increase when immersed in air. The low thermal diffusivity for the cluster in water suggests poor thermal contact between the cluster and the thermal bath. The lithographically prepared nanodot has much better adhesion to the AlGaN film, resulting in much higher thermal diffusivity in both air and water. This proof-of-concept demonstration opens a new way to measure the dynamics of the local heat generation and dissipation at the nanoparticle-media interface.

In Situ Sensing of Reactive Oxygen Species on Dye-Stained Single DNA Molecules under Illumination.

Reactive oxygen species (ROS) are a necessary evil in many biological systems and have been measured with fluorescent probes at the ensemble levels both in vitro and in vivo. Measuring ROS generated from a single molecule is important for mechanistic studies, yet measuring ROS near a dye-labeled single-molecule under illumination has been challenging. Here, we use CellROX, a group of ROS probes, to sense ROS near dye-stained DNA that has been flow-stretched and immobilized on a surface. ROS is responsible for the photodamage of DNA molecules under this circumstance. In this report, we confirmed the ROS sensing reaction in bulk solutions and optimized the conditions for single-molecule experiments including the selection of substrates, dye concentrations, probes in the CellROX series, excitation lasers, and emission filter-sets. We observed a correlation between ROS and the dye-labeled DNA and localized the ROS-activated CellROX probe molecules at both the ensemble level and the single-molecule level.

Development of an Integrated Syringe-Pump-Based Environmental-Water Analyzer ( iSEA) and Application of It for Fully Automated Real-Time Determination of Ammonium in Fresh Water.

The development of a multipurpose integrated syringe-pump-based environmental-water analyzer ( iSEA) and its application for spectrophotometric determination of ammonium is presented. The iSEA consists of a mini-syringe pump equipped with a selection valve and laboratory-programmed software written by LabVIEW. The chemistry is based on a modified indophenol method using o-phenylphenol. The effect of reagent concentrations and sample temperatures was evaluated. This fully automated analyzer had a detection limit of 0.12 µM with sample throughput of 12 h-1. Relative standard deviations at different concentrations (0-20 µM) were 0.23-3.36% ( n = 3-11) and 1.0% ( n = 144, in 24 h of continuous measurement, ∼5 µM). Calibration curves were linear ( R2 = 0.9998) over the range of 0-20 and 0-70 µM for the detection at 700 and 600 nm, respectively. The iSEA was applied in continuous real-time monitoring of ammonium variations in a river for 24 h and 14 days. A total of 1802 samples were measured, and only 0.4% was outlier data (≥3 sigma residuals). Measurements of reference materials and different aqueous samples ( n = 26) showed no significant difference between results obtained by reference and present methods. The system is compact (18 cm × 22 cm × 24 cm), portable (4.8 kg), and robust (high-resolution real-time monitoring in harsh environments) and consumes a small amount of chemicals (20-30 µL/run) and sample/standards (2.9 mL/run).

Successive Surface Reactions on Hydrophilic Silica for Modified Magnetic Nanoparticle Attachment Probed by Sum-Frequency Generation Spectroscopy.

Successive surface reactions on hydrophilic silica substrates were designed and performed to immobilize ethanolamine-modified magnetic ferrite-based nanoparticle (NP) for surface characterization. The various surfaces were monitored using sum-frequency generation (SFG) spectroscopy. The surface of the hydrophilic quartz substrate was first converted to a vinyl-terminated surface by utilizing a silanization reaction, and then, the surface functional groups were converted to carboxylic-terminated groups via a thiol-ene reaction. The appearance and disappearance of the vinyl (═CH2) peak at ∼2990 cm-1 in the SFG spectra were examined to confirm the success of the silanization and thiol-ene reactions, respectively. Acyl chloride (-COCl) formation from carboxy (-COOH) functional group was then performed for further attachment of magnetic amine-functionalized magnesium ferrite nanoparticles (NPs) via amide bond formation. The scattered NPs attached on the modified silica substrate was then used to study the changes in the spectral profile of the ethanolamine modifier of the NPs for in situ lead(II) (Pb2+) adsorption at the solid-liquid interface using SFG spectroscopy. However, due to the limited number of NPs attached and sensitivity of SFG spectroscopy toward expected change in the modifier spectroscopically, no significant change was observed in the SFG spectrum of the modified silica with magnetic NPs during exposure to Pb2+ solution. Nevertheless, SFG spectroscopy as a surface technique successfully monitored the modifications from a clean fused substrate to -COCl formation that was used to immobilize the decorated magnetic nanoparticles. The method developed in this study can provide a reference for many surface or interfacial studies important for selective attachment of adsorbed organic or inorganic materials or particles.

Ultrafast Transient Absorption Spectra of Photoexcited YOYO-1 molecules call for additional investigations of their fluorescence quenching mechanism.

In this report, we observed that YOYO-1 immobilized on a glass surface is much brighter when dried (quantum yield 16±4% in the ambient air) or in hexane than in water (quantum yield ~%).YOYO-1 is a typical cyanine dye that has a photo-isomerization reaction upon light illumination. In order to understand this quenching mechanism, we use femtosecond transient absorption spectroscopy to measure YOYO-1's electron dynamics after excitation directly. By deconvoluting the hot-ground-state absorption and the stimulated emission, the dynamics of electronic relaxation and balance are revealed. The results support the intermolecular charge transfer mechanism better than the intramolecular relaxation mechanism that has been widely believed before. We believe that the first step of the relaxation involves a Dexter charge transfer between the photo-excited YOYO-1 molecule and another guest molecule that is directly bound to the YOYO-1 giving two radicals with opposite signs of charges. The charges are recombined either directly between these two molecules, or both molecules start to rotate and separate from each other. Eventually, the two charges recombined non-radiatively via various pathways. These pathways are reflected on the complicated multi-exponential decay curves of YOYO-1 fluorescence lifetime measurements. This charge transfer mechanism suggests that (1) electrical insulation may help improve the quantum yield of YOYO-1 in polar solutions significantly and (2) a steric hindrance for the intramolecular rotation may have a less significant effect.

The Role of Thermal Activation and Molecular Structure on the Reaction of Molecular Surfaces.

Though surface modifications of organic thin films dramatically improve optoelectronic device performance, chemistry at organic surfaces presents new challenges that are not seen in conventional inorganic surfaces. This work demonstrates that the subsurface of pentacene remains highly accessible, even to large adsorbates, and that three distinct reaction regimes (surface, subsurface, and bulk) are accessed within the narrow thermal range of 30-75 °C. Progression of this transition is quantitatively measured via polarization modulation infrared reflection absorption spectroscopy, and atomic force microscopy is used to measure the thin-film morphology. Together, they reveal the close relationship between the extent of the reaction and the morphology changes. Finally, the reaction kinetics of the pentacene thin film is measured with a series of adsorbates that have different reactivity and diffusivity in the thin film. The results suggest that reaction kinetics in the thin film is controlled by both the reactivity and the adsorbate diffusivity in the thin-film lattice, which is very different than the traditional solution kinetics that is dominated by the chemical activation barriers. Combined, these experiments guide efforts toward rationally functionalizing the surfaces of organic semiconductors to enable the next generation of flexible devices.

Unified superresolution experiments and stochastic theory provide mechanistic insight into protein ion-exchange adsorptive separations.

Chromatographic protein separations, immunoassays, and biosensing all typically involve the adsorption of proteins to surfaces decorated with charged, hydrophobic, or affinity ligands. Despite increasingly widespread use throughout the pharmaceutical industry, mechanistic detail about the interactions of proteins with individual chromatographic adsorbent sites is available only via inference from ensemble measurements such as binding isotherms, calorimetry, and chromatography. In this work, we present the direct superresolution mapping and kinetic characterization of functional sites on ion-exchange ligands based on agarose, a support matrix routinely used in protein chromatography. By quantifying the interactions of single proteins with individual charged ligands, we demonstrate that clusters of charges are necessary to create detectable adsorption sites and that even chemically identical ligands create adsorption sites of varying kinetic properties that depend on steric availability at the interface. Additionally, we relate experimental results to the stochastic theory of chromatography. Simulated elution profiles calculated from the molecular-scale data suggest that, if it were possible to engineer uniform optimal interactions into ion-exchange systems, separation efficiencies could be improved by as much as a factor of five by deliberately exploiting clustered interactions that currently dominate the ion-exchange process only accidentally.

Conformational transitions in the glycine-bound GluN1 NMDA receptor LBD via single-molecule FRET.

The N-methyl-D-aspartate receptor (NMDAR) is a member of the glutamate receptor family of proteins and is responsible for excitatory transmission. Activation of the receptor is thought to be controlled by conformational changes in the ligand binding domain (LBD); however, glutamate receptor LBDs can occupy multiple conformations even in the activated form. This work probes equilibrium transitions among NMDAR LBD conformations by monitoring the distance across the glycine-bound LBD cleft using single-molecule Förster resonance energy transfer (smFRET). Recent improvements in photoprotection solutions allowed us to monitor transitions among the multiple conformations. Also, we applied a recently developed model-free algorithm called "step transition and state identification" to identify the number of states, their smFRET efficiencies, and their interstate kinetics. Reversible interstate conversions, corresponding to transitions among a wide range of cleft widths, were identified in the glycine-bound LBD, on much longer timescales compared to channel opening. These transitions were confirmed to be equilibrium in nature by shifting the distribution reversibly via denaturant. We found that the NMDAR LBD proceeds primarily from one adjacent smFRET state to the next under equilibrium conditions, consistent with a cleft-opening/closing mechanism. Overall, by analyzing the state-to-state transition dynamics and distributions, we achieve insight into specifics of long-lived LBD equilibrium structural dynamics, as well as obtain a more general description of equilibrium folding/unfolding in a conformationally dynamic protein. The relationship between such long-lived LBD dynamics and channel function in the full receptor remains an open and interesting question.

Charge-dependent transport switching of single molecular ions in a weak polyelectrolyte multilayer.

The tunable nature of weak polyelectrolyte multilayers makes them ideal candidates for drug loading and delivery, water filtration, and separations, yet the lateral transport of charged molecules in these systems remains largely unexplored at the single molecule level. We report the direct measurement of the charge-dependent, pH-tunable, multimodal interaction of single charged molecules with a weak polyelectrolyte multilayer thin film, a 10 bilayer film of poly(acrylic acid) and poly(allylamine hydrochloride) PAA/PAH. Using fluorescence microscopy and single-molecule tracking, two modes of interaction were detected: (1) adsorption, characterized by the molecule remaining immobilized in a subresolution region and (2) diffusion trajectories characteristic of hopping (D ∼ 10(-9) cm(2)/s). Radius of gyration evolution analysis and comparison with simulated trajectories confirmed the coexistence of the two transport modes in the same single molecule trajectories. A mechanistic explanation for the probe and condition mediated dynamics is proposed based on a combination of electrostatics and a reversible, pH-induced alteration of the nanoscopic structure of the film. Our results are in good agreement with ensemble studies conducted on similar films, confirm a previously-unobserved hopping mechanism for charged molecules in polyelectrolyte multilayers, and demonstrate that single molecule spectroscopy can offer mechanistic insight into the role of electrostatics and nanoscale tunability of transport in weak polyelectrolyte multilayers.