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Articular cartilage is one of the most important weight-bearing components in human body, thus the chondrogenesis of stem cells is reactive to many intracellular and extracellular mechanical signals. As a unique physical cue, matrix stiffness plays an integral role in commitment of stem cell fate. However, when examining the downstream effects of matrix stiffness, most studies used different soluble factors to assist physical inducing process, which may mask the chondrogenic effects of matrix stiffness. Here we fabricated polyacrylamide (PAAm) hydrogels with gradient stiffness to unravel the role of matrix stiffness in chondrogenic process of mesenchymal stem cells (MSCs), with or without TGF-β3 as induction factor. The results showed that with micromass culture mimicking relatively high cell density in vivo, the chondrogenic differentiation of MSCs can be promoted by soft substrates (about 0.5 kPa) independently with assembled cytoskeleton. Further analysis indicated that addition of TGF-β3 generally increased expression level of cartilage-related markers and masked the stiffness-derived expression pattern of hypertrophic markers. These results demonstrate how mechanical cues experienced in developmental context regulate commitment of stem cell fate and have significant impact on the design of tissue regeneration materials.

Objectives: Cephalometric analysis is essential for diagnosis, treatment planning and outcome assessment of orthodontics and orthognathic surgery. Utilizing artificial intelligence (AI) to achieve automated landmark localization has proved feasible and convenient. However, current systems remain insufficient for clinical application, as patients exhibit various malocclusions in cephalograms produced by different manufacturers while limited cephalograms were applied to train AI in these systems. Methods: A robust and clinically applicable AI system was proposed for automatic cephalometric analysis. First, 9870 cephalograms taken by different radiography machines with various malocclusions of patients were collected from 20 medical institutions. Then 30 landmarks of all these cephalogram samples were manually annotated to train an AI system, composed of a two-stage convolutional neural network and a software-as-a-service system. Further, more than 100 orthodontists participated to refine the AI-output landmark localizations and retrain this system. Results: The average landmark prediction error of this system was as low as 0.94 ± 0.74 mm and the system achieved an average classification accuracy of 89.33%. Conclusions: An automatic cephalometric analysis system based on convolutional neural network was proposed, which can realize automatic landmark location and cephalometric measurements classification. This system showed promise in improving diagnostic efficiency in clinical circumstances.

Osteoporosis is a widespread disease characterized by bone mass loss and microarchitectural deterioration. The side effects of clinical drugs make mesenchymal stem cells (MSCs)-based therapy gain increasing focus in the treatment of osteoporosis. MSCs need to migrate to the site of damage and undergo differentiation in order to participate in the subsequent bone repair process. Therefore, the homing ability of MSCs may be related to the repair ability. Here, we proposed a novel method to screen MSCs with high migration capacity and confirmed that these MSCs exhibited higher osteogenic differentiation ability both in vivo and in vitro. Further results indicated that MSCs with high migration ability could partly rescue the bone loss of ovarectomized (OVX) rats. Higher expression of Platelet-derived growth factors receptor β- (PDGFRβ) and more nuclear transduction of β-catenin in MSCs with high migration ability may be responsible for biological functions. This article may provide a method to improve the efficacy of MSCs-based therapy in the clinic.

Objective. Cephalometric analysis has been significantly facilitated by artificial intelligence (AI) in recent years. For digital cephalograms, linear measurements are conducted based on the length calibration process, which has not been automatized in current AI-based systems. Therefore, this study aimed to develop an automated calibration system for lateral cephalometry to conduct linear measurements more efficiently. Approach. This system was based on deep learning algorithms and medical priors of a stable structure, the anterior cranial base (Sella–Nasion). First, a two-stage cascade convolutional neural network was constructed based on 2860 cephalograms to locate sella, nasion, and 2 ruler points in regions of interest. Further, Sella–Nasion distance was applied to estimate the distance between ruler points, and then pixels size of cephalograms was attained for linear measurements. The accuracy of automated landmark localization, ruler length prediction, and linear measurement based on automated calibration was evaluated with statistical analysis. Main results. First, for AI-located points, 99.6% of S and 86% of N points deviated less than 2 mm from the ground truth, and 99% of ruler points deviated less than 0.3 mm from the ground truth. Also, this system correctly predicted the ruler length of 98.95% of samples. Based on automated calibration, 11 linear cephalometric measurements of the test set showed no difference from manual calibration (p > 0.05). Significance. This system was the first reported in the literature to conduct automated calibration with high accuracy and showed high potential for clinical application in cephalometric analysis.

Gene mining in a C. lanatus × C. amarus population revealed one gene, ACS7, linked to primary root elongation in watermelon. Watermelon is a xerophytic crop characterized by a long primary root and robust lateral roots. Therefore, watermelon serves as an excellent model for studying root elongation and development. However, the genetic mechanism underlying the primary root elongation in watermelon remains unknown. Herein, through bulk segregant analysis we identified a genetic locus, qPRL.Chr03, controlling primary root length (PRL) using two different watermelon species (Citrullus lanatus and Citrullus amarus) that differ in their root architecture. Fine mapping revealed that xaa-Pro dipeptidase and 1-aminocyclopropane-1-carboxylate synthase 7 (ACS7) are candidate regulators of the primary root growth. Allelic variation in the delimited region among 193 watermelon accessions indicated that the long-root alleles might only exist in C. amarus. Interestingly, the discrepancy in PRL among the C. amarus accessions was clearly associated with a nonsynonymous single nucleotide polymorphism variant within the ACS7 gene. The ACS7 expression and ethylene levels in the primary root tips suggested that ethylene is a negative regulator of root elongation in watermelon, as supported by the application of 1-aminocyclopropane-1-carboxylate (ACC, the ethylene precursor) or 2-aminoethoxyvinyl glycine (AVG, an ACS inhibitor). To the best of our knowledge, these findings provide the first description of the genetic basis of root elongation in watermelon. The detected markers of the ACS7 gene will facilitate marker-assisted selection for the PRL trait to improve water and nutrient use efficacy in watermelon and beyond.

A software package to be used in high-speed oscilloscope-based three-dimensional bunch-by-bunch charge and position measurement is presented. The software package takes the pick-up electrode signal waveform recorded by the high-speed oscilloscope as input, and it calculates and outputs the bunch-by-bunch charge and position. In addition to enabling a three-dimensional observation of the motion of each passing bunch on all beam position monitor pick-up electrodes, it offers many additional features such as injection analysis, bunch response function reconstruction, and turn-by-turn beam analysis. The software package has an easy-to-understand graphical user interface and convenient interactive operation, which has been verified on the Windows 10 system.

In order to improve machine performance, the optics parameters of the storage ring need to be measured accurately. The commonly used accelerator optics parameters, including momentum compaction factor and dispersion function, are key parameters that reflect the state of the machine. It is difficult to measure them with traditional methods during the user operation run. Based on a high-resolution bunch-by-bunch three-dimensional measurement system, a noninvasive measurement of momentum compaction factor and the dispersion function was performed at the Shanghai synchrotron radiation facility (SSRF). The dispersion function can be obtained purely from the direct observation results of the bunch-by bunch 3D position, based on the definition of the dispersion function during normal user operation run without perturbing the beam. The theoretical background and experimental results of the method are discussed in this paper. The measurement results are in good agreement with the design values.

Bunch-by-bunch beam parameters monitor is a very useful tool for accelerator operation and optimization. An in situ bunch-by-bunch three-dimensional position and charge measurement system has been developed at the Shanghai Synchrotron Radiation Facility. Signals from beam position monitors carry almost full beam information, a broadband digital receiver can retain most information. Therefore, a four-channel wideband oscilloscope is employed to capture the signals from all electrodes of the beam position monitor. Correlation coefficient-based methods are used to extract these bunch-by-bunch parameters synchronously. We evaluated the performance of this bunch-by-bunch information extraction method, the measurement uncertainty of longitudinal phase is less than 0.2 ps, the uncertainty of transverse position is less than $10\text{ }\text{ }\ensuremath{\mu}\mathrm{m}$ and the charge uncertainty is 0.3% under the condition that the bunch charge is 600 pC. Thanks to the great performance of the new system, it is accurate enough to study the transient state during injection. In addition, an in situ wakefield measurement system is planned to be established based on this system.

We report on the application of machine learning (ML) methods to extract longitudinal phase information such as parameters of the synchrotron damping oscillation. Parameters of the synchrotron damping oscillation are important for the evaluation of machine status and bunch stability. It is of concern to extract these parameters with high-speed and high-precision. The previous methods, such as multiparameter nonlinear fitting and table look-up, are slower and easily fall into local optimal solutions. Our approach based on ML-image processing consists of training a virtual diagnostic to predict parameters using the beam position monitor (BPM) electrical signal data as inputs. We find that when the noise of data is large, our ML-model can still get better results than other methods, an important step toward on-line multiparameter extraction from multidimensional raw data.

Lifetime is a key performance parameter of storage rings. DC current transformers (DCCT) are common employed to measure beam lifetime, which can only be applied to measure average lifetime. However, the physical lifetime formula is only strictly established for a single bunch. In order to provides a toolkit for complete and accurate representation of the behavior of all electron bunches, a bunch-by-bunch beam lifetime measurement system has been developed at the Shanghai Synchrotron Radiation Facility. A beam-position-monitor was used as the detector of beam-charge-monitor. Several effective techniques have been introduced to improve the resolution and data refresh rate of the single bunch charge measurement. Resolution of the new bunch-by-bunch charge monitor is better than 0.02% and data refresh rate is 140 Hz. A dedicated algorithm has been developed to extract lifetime of single bunch. Resolution of bunch-by-bunch vacuum lifetime measurement is 1 h. System setup, experiments and data analysis are presented in this paper.

Cavity Beam Position Monitor (CBPM) adopting a resonant cavity structure and using the characteristic modes excited by the electron beam to measure the beam parameters, has the advantage of high position resolution and is widely used in Free-electron Laser (FEL) facilities. The wake field of different modes carries different bunch information, the amplitude and phase of the signals of different modes can be extracted through the signal processing method to obtain the characteristic parameters of the source bunch. In the application of bunch charge and position measurement, the accurate amplitude extraction method for cavity BPM signal is the primary issue to be considered when designing the data acquisition and processing system. In this paper, through theoretical analysis and numerical simulation, it is proved that the optimal algorithm of amplitude extraction for CBPM exists, and the dependence between the data processing window size and the decay time of the cavity BPM under the optimal design is given. In addition, the relationship between the optimized amplitude extraction uncertainty and the noise-to-signal ratio, sampling rate of data acquisition and processing system, and the decay time of the cavity BPM is also proposed, which can provide clear guidance for the design and optimization of the CBPM system. Accordingly, the CBPM system in Shanghai Soft X-ray FEL (SXFEL) facility is optimized, and the resolution improved from 273 nm to 177 nm at the bunch charge of 500 pC.

Continuous tracking of bunch charges is the key to maintain stable operations in a storage ring in top-up mode. Recently, a precise bunch-by-bunch beam-current measurement (BCM) system has been developed at the Shanghai Synchrotron Radiation Facility. To avoid the influence of longitudinal oscillation on the amplitudes of the sampling points, a method called two-point equilibrium sampling is introduced. The results, obtained during routine operation time, show that the relative resolution of the measurement of the bunch charges is better than 0.02%. With this high resolution, the new BCM system is able to monitor the bunch-by-bunch beam lifetime. By using the filling pattern information, the Touschek lifetime and the vacuum lifetime can also be calculated. In this paper, the principle of the new method and the experiments is presented in detail.

Contactin-associated protein-like 2 (CNTNAP2 or CASPR2) is a neuronal transmembrane protein of the neurexin superfamily that is involved in many neurological diseases, such as autism and pain hypersensitivity. We recently found that Cntnap2−/− mice showed elevated Akt-mTOR activity in the brain, and suppression of the Akt-mTOR pathway rescued the social deficit in Cntnap2−/− mice. In this study, we found that the dorsal root ganglion (DRG) from Cntnap2−/− mice also showed hyperactive Akt-mTOR signaling. Treatment with the Akt inhibitor LY94002 or the mTOR inhibitor rapamycin attenuated pain-related hypersensitivity to noxious mechanical stimuli, heat, and inflammatory substances. Further, suppression of mTOR signaling by rapamycin decreased DRG neuronal hyperexcitability. We further indicated that treatment with the FDA-approved drug metformin normalized the hyperactive Akt-mTOR signaling, and attenuated pain-related hypersensitivity in Cntnap2−/− mice. Our results thus identified hyperactive Akt-mTOR signaling pathway as a promising therapeutic target for pain-related hypersensitivity in patients with dysfunction of CNTNAP2.

A high-resolution bunch-by-bunch longitudinal phase measurement system has been developed at the Shanghai Synchrotron Radiation Facility. The system has a high-speed digital signal analyzer to capture the signals from a beam-position-monitor. Then the bunch phases can be collected by using a zero-crossing detection method and a longitudinal delta-over-sum lookup table method consecutively. The phase of the refilled charge is calculated by separating it from the stored bunch. In order to fully explore the evolution of the refilled charge damping oscillation, the transient state during injection was further studied. The arrival time of the refilled charge, the energy mismatch between the injector and the storage ring, and the synchrotron damping time can be obtained in the injection transient process. This system is capable of measuring the bunch-by-bunch phases online, which provides an additional way to monitor the machine status or to optimize the injector.

Beam signals captured from a button-type pickup contain multidimensional information including the bunch charge, transverse position, bunch length, and longitudinal phase. A bunch phase monitor, which retrieves longitudinal phase information from a pickup signal at a bunch-by-bunch rate, has been developed at the Shanghai Synchrotron Radiation Facility. This paper introduces the basic principles, system setup, data processing method, and preliminary experimental results of this system. The systematic measurement error introduced by the limited system bandwidth, bunch length, and bunch charge variation was studied using simulation data. The random measurement uncertainty was evaluated using experimental beam data. The experimental result shows that the longitudinal phase resolution of this system is better than 1.0 ps. The first application, measuring the relationship between the longitudinal phase and bunch charge to determine the energy loss factor, was implemented, and the preliminary result is also discussed.

A systematic review of the Chinese literature was conducted from 1956 to 2005. The survey included both online and manual searching, as well as expert discussions aimed at providing insight into factors affecting benzene exposure levels in paint/coatings industries. Data extracted from 204 papers included: (1) year of occurrence, (2) type of paint/coatings products, (3) type of industries where the products were used or produced, (4) job titles and work activities, (5) type of literature searched, (6) working conditions whenever data were available, and (7) exposure levels. Most benzene measurements were short-term samples for comparison with the Chinese maximum allowable concentration standard. The accuracy and precision of the sampling and analytical methods were not reported. The distribution of benzene concentrations was tested and found to fit neither normal nor lognormal distributions. Analysis of variance (comparison for more than two groups) and t-test (comparison for two groups) were conducted on Blom-transformed benzene concentration data. The overall median benzene exposure levels were 215, 82, 31, and 6 mg/m(3) during the periods 1956-1978, 1979-1989, 1990-2001, and 2002-2005, respectively. Mean benzene exposure was significantly lower for paint manufacturing than paint spraying. No significant difference was found among paint types and benzene exposure for paint application. Benzene exposure was significantly higher in workplaces judged to have poor ventilation. No significant differences were found in benzene exposure as a function of industry type. Even though substantially lower when compared with levels in the past, recent benzene exposure measurements suggested that many facilities in the paint/coatings industries in China still have benzene concentrations that are above the current China occupational exposure limit for benzene (6 mg/m(3) as a time-weighted average). Benzene concentrations from the present exercise, while not directly supporting quantitative retrospective exposure estimating, provide insight on relative benzene exposure for painting tasks in the reported industries over time.

This article presents a summary of benzene exposure levels in the shoemaking industry in China reported in the Chinese medical literature between 1978 and 2004. A comprehensive search identified 182 papers reporting such exposure data. These papers could be classified into two categories: benzene poisoning case reports and industrial hygiene surveys. From each paper, the following information was abstracted whenever available: location and year of occurrence, occupation and/or task involved, benzene content in adhesives/solvents, work environment, working conditions, working hours, diagnosis, and air monitoring data of benzene. A total of 333 benzene measurements (88 averages, 116 minimums, 129 maximums) in the shoemaking industry were reported in the 182 papers identified. The data were analyzed in terms of geographical location, time period, type of ownership (state, township, or foreign), type of report (benzene poisoning reports vs. industrial hygiene surveys), and job title (work activity) or process. The reported data covered a wide range; some measurements were in excess of 4500 mg/m(3). Thirty-five percent of the reported benzene concentrations were below 40 mg/m(3), which was the national occupational exposure limit (OEL) for benzene between 1979 and 2001. The remaining 65% measurements, which exceeded the national OEL in effect at the time, and were distributed as follows: 40-100 mg/m(3), 11%; 100-300 mg/m(3), 21%; 300-500 mg/m(3), 13%; and 500+ mg/m(3), 20%. However, only 24% of the reported measurements after 2002 were below 6 mg/m(3), i.e., Permissible Concentration-Time Weighted Average (PC-TWA) and 10 mg/m(3), i.e., Permissible Concentration-Short Term Exposure Limit (PC-STEL), the newly amended benzene OELs in effect after May 2002. The data demonstrated that the majority of the facilities in the shoemaking industry reported in the literature were not in compliance of the OEL for benzene in effect at the time. Overall, the data show a clear downward trend of benzene exposure levels over the years, particularly after the introduction of the new lower OEL in 2002. Even though substantially lower when compared to levels in the past, current benzene exposure measurements from the literature review suggest that many facilities in the shoemaking industry in China have benzene concentrations that are still above the new OEL. The reported data, stratified by job, year and survey reason, can be used as part of the information and analysis for developing a job-exposure matrix in retrospective exposure assessment and thus may be part of the information used in developing historical exposure estimates in epidemiologic studies of shoe workers.

Hematotoxicity following chronic benzene exposure has been recognized for over a century, although the mechanism remains unknown. We describe a novel form of bone marrow dysplasia in 23 workers exposed to high concentrations of benzene. Distinguishing features of benzene-induced dysplasia include: marked dyserythropoiesis, eosinophilic dysplasia and abnormal cytoplasmic granulation of neutrophilic precursors. Hematophagocytosis, stromal degeneration and bone marrow hypoplasia are also seen. Severe bone marrow dysplasia is frequently accompanied by clonal T cell expansion and alterations in T lymphocyte subsets. No clonal cytogenetic abnormalities were observed. These results suggest that autoimmune-mediated bone marrow injury is an early or predisposing event in the pathogenesis of benzene-induced persistent hematopoietic disease.

This article presents an overview of occupational benzene exposures in China based on data published in Chinese medical journals. The data were derived from 384 reports of benzene poisoning or industrial hygiene surveys published in Chinese medical journals between 1960 and 2003. The following information was extracted whenever available: industry, occupation, task, date, benzene levels, sampling location, workplace descriptions and, for case reports, medical diagnosis. Each paper provided one or more sets of benzene data, each set representing a sampling location or job title with one to several measurements including, mainly, breathing zone area concentration measurements, and much less frequently personal monitoring. Two criteria based on data quality were applied to select suitable data for analyses. The selected exposure data were analyzed by industry and time period. Nine hundred five sets of benzene measurements from 72 industries were reported in the 384 papers selected for this review, and 621 sets (68.6%) presented average benzene concentrations, which covered 55 industries. The distribution of the reported average benzene exposures was skewed with a median of 51.5 mg/m3. The average benzene concentrations were below 100 mg/m3 for 406 (65%) of the 621 reported average concentrations. The medians of the reported averages in mg/m3 for the five industries with the highest exposures were: 124.8 for leather products, 98.7 for electronic devices, 75.4 for machinery, 50.4 for shoes, and 50.3 for office supplies and sports equipment manufacturing. These data describe the concentrations and changing patterns of occupational benzene exposure by industry and time period in China.

Highlight A portion of the cadmium taken up by the hyperaccumulator Sedum alfredii can be apoplasmically transported to the xylem via root apexes and lateral roots, where the suberin lamellae are not well developed., Although the significance of apoplasmic barriers in roots with regards to the uptake of toxic elements is generally known, the contribution of apoplasmic bypasses (ABs) to cadmium (Cd) hyperaccumulation is little understood. Here, we employed a combination of stable isotopic tracer techniques, an ABs tracer, hydraulic measurements, suberin lamellae staining, metabolic inhibitors, and antitranspirants to investigate and quantify the impact of the ABs on translocation of Cd to the xylem in roots of a hyperaccumulating (H) ecotype and a non-hyperaccumulating (NH) ecotype of Sedum alfredii. In the H ecotype, the Cd content in the xylem sap was proportional to hydrostatic pressure, which was attributed to pressure-driven flow via the ABs. The contribution of the ABs to Cd transportation to the xylem was dependent on the Cd concentration applied to the H ecotype (up to 37% at the highest concentration used). Cd-treated H ecotype roots showed significantly higher hydraulic conductance compared with the NH ecotype (76 vs 52 × 10–8 m s–1MPa–1), which is in accordance with less extensive suberization due to reduced expression of suberin-related genes. The main entry sites of apoplasmically transported Cd were localized in the root apexes and lateral roots of the H ecotype, where suberin lamellae were not well developed. These findings highlight the significance of the apoplasmic bypass in Cd hyperaccumulation in hyperaccumulating ecotypes of S. alfredii.

We have developed a gas chromatography–mass spectrometry method for analysis of benzene (BZ) metabolites in human urine and blood. Here we describe peripheral blood concentrations of hydroquinone (HQ 1 ) and catechol (CAT 2 ) in total, protein-bound, and unbound (free) forms obtained from BZ-exposed factory workers and controls. Total and unbound metabolites were directly measured in independent experiments, while bound forms were calculated as [total] − [unbound]. In this subset of a larger study, breathing zone benzene, toluene, and xylene were measured for the duration of a workshift, and end-shift blood samples taken from 143 subjects and controls. Potential lifestyle and environmental influences were assessed by questionnaire and bioassay, and single nucleotide polymorphisms in xenobiotic metabolizing enzymes NQO1, MPO, CYP2E1, and GSTT1 were also analyzed for potential contribution to differences in blood metabolite concentration. Total CAT, bound CAT, total HQ, and bound HQ correlated well with benzene exposure, while unbound CAT and HQ displayed no correlation. Nearly all of the metabolites found in blood were bound to protein (CAT 96–99+%, HQ 78–92+%), and when the ratio of bound to unbound metabolites were compared in subsets of exposed workers, the increase in blood metabolite concentration was nearly all due to an increase in the protein-bound molecule. These findings suggest that a threshold for conjugation does not exist within the exposure spectrum studied (0.01–78.8 mg/m 3 ). This method demonstrates the feasibility of analyzing benzene metabolites in human blood, and should allow for further investigation of the health effects of benzene and its metabolites.

The hematotoxic effects of benzene exposure may be important in the occurrence of subsequent health effects. We sought to provide further information on peripheral blood effects by studying 928 workers in five factories in and around Shanghai, China exposed to a wide range of benzene concentrations. Specifically, we sought to investigate which blood indices are more strongly related to benzene exposure and which concentration levels of benzene result in peripheral blood changes. Lifestyle habits and demographic information was obtained via questionnaire, and potentially important genetic influences were determined by assessing single nucleotide polymorphisms in four genes (NQO1, MPO, CYP2E1, GSTT1). Weekly benzene exposure estimated from individual monitoring results ranged from 0.07 to 872 mg/m(3) with a median value of 7.4 mg/m(3). Twelve peripheral blood indices were examined. Stronger effects on peripheral blood were seen for red cell indices such as anemia and macrocytosis, albeit at higher (>10 ppm) exposure levels. The most sensitive parameters to benzene appeared to be neutrophils and the mean platelet volume (MPV), where effects were seen for benzene air concentrations of 7.8-8.2 ppm. Toluene exposure is a potential confounder for some peripheral blood effects, pointing to the need to scrutinize levels of both compounds in the occupational environment.

Recent optical, physical, and biological oceanographic observations are used to assess the magnitude and variability of the penetrating flux of solar radiation through the mixed layer of the warm water pool (WWP) of the western equatorial Pacific Ocean. Typical values for the penetrative solar flux at the climatological mean mixed layer depth for the WWP (30 m) are approx. 23 W/sq m and are a large fraction of the climatological mean net air-sea heat flux (approx. 40 W/sq m). The penetrating solar flux can vary significantly on synoptic timescales. Following a sustained westerly wind burst in situ solar fluxes were reduced in response to a near tripling of mixed layer phytoplankton pigment concentrations. This results in a reduction in the penetrative flux at depth (5.6 W/sq m at 30 m) and corresponds to a biogeochemically mediated increase in the mixed layer radiant heating rate of 0.13 C per month. These observations demonstrate a significant role of biogeochemical processes on WWP thermal climate. We speculate that this biogeochemically mediated feedback process may play an important role in enhancing the rate at which the WWP climate system returns to normal conditions following a westerly wind burst event.