Search

Abstract Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations. Mechanistically, RAB17 attenuated ferroptosis in EC cells by inhibiting transferrin receptor (TFRC) protein expression in a ubiquitin proteasome-dependent manner. Because EC is a blood-deprived tumor with a poor energy supply, the relationship between RAB17 and hypoglycemia was investigated. RAB17 expression was increased in EC cells incubated in low-glucose medium. Moreover, low-glucose medium limited EC cell ferroptosis and promoted EC progression through the RAB17-TFRC axis. The in vitro results were corroborated by in vivo studies and clinical data. Overall, the present study revealed that increased RAB17 promotes the survival of EC cells during glucose deprivation by inhibiting the onset of TFRC-dependent ferroptosis.

Searching social media to find relevant semantic domains often results in large text files, many of which are irrelevant due to cross-domain content resulting from word polysemy, abstractness, and degree centrality. Through an iterative pruning process, Cascaded Semantic Fractionation (CSF) systematically removes these cross-domain links. The social network procedure performs community detection in semantic networks, locates the semantic groups containing the terms of interest, excludes intergroup links, and repeats community detection on the pruned intragroup network until the domain of interest is clarified. To illustrate CSF, we analyzed public Facebook posts, using the CrowdTangle app for historical data search, from February 3, 2020, to March 13, 2021, about the possible Wuhan lab leak of COVID-19 over a daily interval. The initial search using keywords located six multi-day bursts of posts of more than 500 per day among 95 K posts. These posts were network analyzed to find the domain of interest using the iterative community detection and pruning process. CSF can be applied to capture the evolutions in semantic domains over time. At the outset, the lab leak theory was presented in conspiracy theory terms. Over time, the conspiratorial elements washed out in favor of an accidental release as the issue moved from social to mainstream media and official government views. CSF identified the relevant social media semantic domain and tracked its changes.

Abstract Dendrimers are a family of nano‐sized three‐dimensional polymers with unique dendritic branching structures and compact spherical geometries. In recent years, dendrimers have made a series of breakthroughs in the biomedical field. In this review, we introduce the synthesis principles, modification methods, and new materials designed based on dendrimers; discuss the importance of cytotoxicity of dendrimers for applications; and elaborate on their applications in the field of molecular assembly and cancer diagnosis and treatment. We speculate that in the near future, more new materials based on dendrimers will be applied in the biomedical field.

Here the authors report the first experimental observation of topological antichiral surface states by constructing a three-dimensional modified Haldane model in a magnetic Weyl photonic crystal.

Abstract Background The Polygonatum cyrtonema Hua rhizomes (also known as Rhizoma Polygonati, RP) are consumed for their health benefits. The main source of the RP is wild P. cyrtonema populations in the Hunan province of China. However, the soil Cadmium (Cd) content in Huanan is increasing, thus increasing the risks of Cd accumulation in RP which may end up in the human food chain. To understand the mechanism of Cd accumulation and resistance in P. cyrtonema, we subjected P. cyrtonema plants to four levels of Cd stress [(D2) 1, (D3) 2, (D4) 4, and (D5) 8 mg/kg)] compared to (D1) 0.5 mg/kg. Results The increase in soil Cd content up to 4 mg/kg resulted in a significant increase in tissue (root hair, rhizome, stem, and leaf) Cd content. The increase in Cd concentration variably affected the antioxidant enzyme activities. We could identify 14,171 and 12,115 protein groups and peptides, respectively. There were 193, 227, 260, and 163 differentially expressed proteins (DEPs) in D2, D3, D4, and D5, respectively, compared to D1. The number of downregulated DEPs increased with an increase in Cd content up to 4 mg/kg. These downregulated proteins belonged to sugar biosynthesis, amino acid biosynthesis-related pathways, and secondary metabolism-related pathways. Our results indicate that Cd stress increases ROS generation, against which, different ROS scavenging proteins are upregulated in P. cyrtonema. Moreover, Cd stress affected the expression of lipid transport and assembly, glycolysis/gluconeogenesis, sugar biosynthesis, and ATP generation. Conclusion These results suggest that an increase in soil Cd content may end up in Huangjing. Cadmium stress initiates expression changes in multiple pathways related to energy metabolism, sugar biosynthesis, and secondary metabolite biosynthesis. The proteins involved in these pathways are potential candidates for manipulation and development of Cd stress-tolerant genotypes.

Based on the hourly surface ozone (O3) observations and meteorological data from Zhuzhou in 2021, the pollution characteristics and influencing factors of O3 in Zhuzhou were investigated in the study. In addition, the Potential Source Contribution Function (PSCF) and Concentration Weighted Trajectory (CWT) analysis methods were employed to analyze the transmission paths and potential pollution sources of O3 pollution in Zhuzhou. The results showed that the total number of days with O3 exceeding the standard at all monitoring stations in Zhuzhou was 142 days in 2021. The overall air quality was less affected by SO2, NO2, and CO, and the trend of O3 pollution was still increasing. The concentrations of O3, CO, and NO2 varied significantly in different months, and the variation of O3 exhibited a “double-peak” pattern, with the peak value occurring in September. The O3 concentration in urban areas was significantly higher than that in suburban areas. Meteorological conditions had a significant impact on the degree of O3 pollution in Zhuzhou. The average wind speed in Zhuzhou throughout the year was 1.7 m/s, and the prevailing wind direction in summer was southeast, with a frequency of 16%. O3 pollution was mainly transported by short-distance airflow during the over-standard periods in 2021, accounting for 37.64%. The main source of O3 pollutant was from Jiangxi Province in the east, with the shortest distance of regional transport and the highest O3 concentration. In addition, transportation from central Guangdong Province, western Jiangxi Province, and central Hubei Province also had a significant impact.

Abstract Patients with advanced melanoma have shown an improved outlook after anti-PD1 therapy, but the low response rate restricts clinical benefit; therefore, enhancing anti-PD1 therapeutic efficacy remains a major challenge. Here, our findings showed a significantly increased abundance of α-KG in healthy controls, anti-PD1-sensitive melanoma-bearing mice, and anti-PD1-sensitive melanoma patients; moreover, supplementation with α-KG enhanced the efficacy of anti-PD1 immunotherapy and increased PD-L1 expression in melanoma tumors via STAT1/3. We also found that supplementation with α-KG significantly increased the activity of the methylcytosine dioxygenases TET2/3, which led to an increased 5-hydroxymethylcytosine (5-hmC) level in the PD-L1 promoter. As a consequence, STAT1/3 binding to the PD-L1 promoter was stabilized to upregulate PD-L1 expression. Importantly, single-cell sequencing of preclinical samples and analysis of clinical data revealed that TET2/3-STAT1/3-CD274 signaling was associated with sensitivity to anti-PD1 treatment in melanoma. Taken together, our results provide novel insight into α-KG’s function in anti-PD1 treatment of melanoma and suggest supplementation with α-KG as a novel promising strategy to improve the efficacy of anti-PD1 therapy.

Abstract Background Phytoremediation is a potentially cost-effective way to remediate highly contaminated mine tailing sites. However, nutrient limitations, especially the deficiency of nitrogen (N), can hinder the growth of plants and impair the phytoremediation of mine tailings. Nevertheless, pioneer plants can successfully colonize mine tailings and exhibit potential for tailing phytoremediation. Diazotrophs, especially diazotrophic endophytes, can promote the growth of their host plants. This was tested in a mine-tailing habitat by a combination of field sampling, DNA-stable isotope probing (SIP) analysis, and pot experiments. Results Bacteria belonging to the genera Herbaspirillum, Rhizobium, Devosia, Pseudomonas, Microbacterium, and Delftia are crucial endophytes for Chinese silvergrass (Miscanthus sinensis) grown in the tailing, the model pioneer plant selected in this study. Further, DNA-SIP using 15N2 identified Pseudomonas, Rhizobium, and Exiguobacterium as putative diazotrophic endophytes of M. sinensis. Metagenomic-binning suggested that these bacteria contained essential genes for nitrogen fixation and plant growth promotion. Finally, two diazotrophic endophytes Rhizobium sp. G-14 and Pseudomonas sp. Y-5 were isolated from M. sinensis. Inoculation of another pioneer plant in mine tailings, Bidens pilosa, with diazotrophic endophytes resulted in successful plant colonization, significantly increased nitrogen fixation activity, and promotion of plant growth. Conclusions This study indicated that diazotrophic endophytes have the potential to promote the growth of pioneer plant B. pilosa in mine tailings. Video Abstract

In an era of intense partisanship, there is widespread concern that people are self-sorting into separate online communities which are detached from one another. Referred to as echo chambers , the phenomenon is sometimes attributed to the new media landscape and internet ecosystem. Of particular concern is the idea that communication between disparate groups is breaking down due to a lack of a shared reality. In this article, we look to evaluate these assumptions. Applying text and semantic network analyses, we study the language of users who represent distinct partisan political ideologies on Reddit and their discussions in light of the January 6, 2021, Capitol Riots. By analyzing over 58k posts and 3.4 million comments across three subreddits, r/politics, r/democrats, and r/Republican, we explore how these distinct groups discuss political events to understand the possibility of bridging across echo chambers. The findings of this research study provide insight into how members of distinct online groups interpret major political events.

Virtualization technology represented through Virtual Machines (VMs) is recognized as a key infrastructure in cloud computing. This technology is developing rapidly and cloud data centers face challenges such as Virtual Machine Placement (VMP) for energy efficiency. VMP is defined as the efficient allocation of VMs to Host Machines (HMs) to achieve various objectives such as reducing energy consumption, load balancing and avoid Service Level Agreement Violations (SLAV). In this paper, VMP is addressed using a Deep Reinforcement Learning (DRL) based strategy to determine the best mapping between VMs and HMs. We present VMP-A3C, an effective strategy to solve VMP using Asynchronous Advantage Actor-Critic (A3C) algorithm as a new DRL approach. VMP-A3C aims at load balancing in HMs without SLAV, where energy consumption is reduced as much as possible. VMP-A3C learns to dynamically consolidate VMs using migration techniques to a minimum number of HMs. We believe that there is scope for improvements in shutting down little-workload HMs through VMs migration. The effectiveness of the proposed algorithm has been evaluated from various aspects such as the deployment rate, energy consumption, SLAV, the number of shutdown HMs and the number of migrated VMs. The main difference in terms of energy consumption and the number of required HMs between VMP-A3C and the best existing state-of-the-art method is 2.54% and 7.14%, respectively.

Motivated by the need for enhancing sorbent affinity for per- and polyfluoroalkyl substances (PFAS), we demonstrate the possibility of rationally designing clay-based material (FluoroClay) with a pre-selected intercalant and predicting sorbent performance using all-atom molecular dynamics simulation coupled with density functional theory-based computation. Perfluorohexyldodecane quaternary ammonium (F6H12A) as the selected intercalant revealed significant enhancement in adsorption affinity for hard-to-remove compounds, including perfluorobutane sulfonate (PFBS) and polyfluoroalkylethers (GenX and ADONA). The adsorption is thermodynamically entropy-driven and dominated by the hydrophobic effect. The incorporation of fluorine atoms into clay intercalants gave rise to a hydrophobic and fluorophilic “cavity” structure for targeted PFAS. The self-assembly of intercalant-PFAS under the negative electric field of clay sheets created a unique configuration that significantly enlarged the contact surface area between PFAS and F6H12A and was quantitatively driven by their intermolecular interactions, e.g., CF chain-CH chain, CF chain-CF chain, and charge-CH chain interactions. Collectively, our work demonstrated a new approach to select fluorinated functionality for designing a new adsorbent and estimating its performance via molecular simulation. It also provided an in-depth understanding of the underlying fundamental physics and chemistry in the adsorption of PFAS, suggesting a new strategy for PFAS removal, particularly for short-chain PFAS and new chemical alternatives.

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal cells. Although elevated glycolysis flux has been reported in psoriasis, the molecular mechanisms underlying its pathogenesis remain unclear. We investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis, observing its high expression in psoriatic skin lesions of humans and imiquimod (IMQ)-induced mouse models. In mouse models, genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic inflammation. We found that CD147 interacted with glucose transporter 1 (Glut1). Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in vivo. In CD147-knockout mice and keratinocytes, oxidative phosphorylation was increased in the epidermis, indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of psoriasis. Using non-targeted and targeted metabolic techniques, we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid (α-KG). Depletion of CD147 also increased transcriptional expression and activity of γ-butyrobetaine hydroxylase (γ-BBD/BBOX1), a crucial molecule for carnitine metabolism, by inhibiting histone trimethylations of H3K9. Our findings demonstrate that CD147 is critical in metabolic reprogramming through the α-KG–H3K9me3–BBOX1 axis in the pathogenesis of psoriasis, indicating that epidermal CD147 is a promising target for psoriasis treatment.

Abstract Background Exosomes are a promising tool in disease detection because they are noninvasive, cost-effective, sensitive and stable in body fluids. MicroRNAs (miRNAs) are the main exosomal component and participate in tumor development. However, the exosomal miRNA profile among Asian melanoma patients remains unclear. Methods Exosomal miRNAs from the plasma of melanoma patients (n = 20) and healthy individuals (n = 20) were isolated and subjected to small RNA sequencing. Real-time PCR was performed to identify the differential miRNAs and to determine the diagnostic efficiency. Proliferation, scratch and Transwell assays were performed to detect the biological behavior of melanoma cells. Results Exosomal miRNA profiling revealed decreased miR-1180-3p expression as a potential diagnostic marker of melanoma. The validation group of melanoma patients (n = 28) and controls (n = 28) confirmed the diagnostic efficiency of miR-1180-3p. The level of miR-1180-3p in melanoma cells was lower than that in melanocytes. Accordingly, the level of miR-1180-3p was negatively associated with the proliferation, migration and invasion of melanoma cells. Functional analysis and target gene prediction found that ST3GAL4 was a potential target and highly expressed in melanoma tissues and was negatively regulated by miR-1180-3p. Knockdown of ST3GAL4 hindered the malignant phenotype of melanoma cells. Conclusions This study indicates that reduced exosomal miR-1180-3p in melanoma patient plasma is a promising diagnostic marker and provides novel insight into melanoma development.

Background: The current community-based colorectal cancer (CRC) screening program in Shanghai, launched in 2013, invited individuals aged 50–74 years to triennial screening with a qualitative faecal immunochemical test (FIT) and questionnaire-based risk assessment (RA). We aimed to evaluate the effectiveness and cost-effectiveness of the existing Shanghai screening program and compare it to using a validated two-sample quantitative FIT. Methods: We simulated four strategies (no screening, Shanghai FIT, Shanghai FIT + RA and validated FIT) for the Shanghai screening program and evaluated CRC incidence, CRC mortality, the number of life years gained (LYG), the number of FITs, and colonoscopies required for each. An incremental cost-effectiveness analysis was performed to assess the cost- effectiveness of each strategy. Results: All screening modalities reduced CRC incidence and CRC mortality, gained extra number of LYG compared to no screening. Screening using the Shanghai FIT and validated FIT reduced CRC incidence from 45 cases to 43 per 1,000 simulated individuals (4.4%). Incidence was reduced to 42 cases (6.7%) using the Shanghai FIT + RA. All screening strategies reduced CRC mortality by 10.0% (from 10 to 9 deaths) and resulted in 6 to 7 LYG. The validated FIT was the most cost-effective among the evaluated strategies (ICER ¥26,461 per LYG). Conclusions: Our findings show that the current Shanghai screening program is (cost-) effective compared to no screening, but changing to a validated FIT would make the program more efficient.

BackgroundThe classic debate regarding the complex relationships between personal network, social media use, and mental well-being requires renewed examination in the novel context of pandemic-related social isolation.Data and methodWe present two surveys conducted at (i) the earlier months of the pandemic and (ii) the end of large scale social-lockdown measures in the U.S. to explore the social and behavioral antecedents of mental health states relating to social media use. Study 1 tracked the longitudinal changes of personal network, social media use, and anxiety level of a group of individuals (N = 147) over a three-month period during the pandemic. Study 2 replicated and extended the theoretical model to a race-representative U.S. adult sample (N = 258).ResultsBoth studies consistently show that (1) more time on social media worsens anxiety. It also mediates the relationship between personal network size and anxiety. That is, a small personal network predicts more social media use, which is in turn related to increased anxiety. (2) Moreover, the effect of social media use on anxiety is mainly explained by news consumption on social media, rather than non-news related usage. (3) This link’s strength is moderated by one’s perception of COVID-19 impact, such that news consumption on social media increases anxiety more when the perceived impact is higher.ConclusionThese results demonstrate communication technologies’ increasingly critical and multifaceted role in affecting mental health conditions.

Introduction To reduce the burden of colorectal cancer (CRC) in Shanghai, China, a CRC screening programme was commenced in 2013 inviting those aged 50–74 years to triennial screening with a faecal immunochemical test (FIT) and risk assessment. However, it is unknown whether this is the optimal screening strategy for this population. We aimed to determine the optimal CRC screening programme for Shanghai in terms of benefits, burden, harms and cost-effectiveness.Methods Using Microsimulation Screening Analysis-Colon (MISCAN-Colon), we estimated the costs and effects of the current screening programme compared with a situation without screening. Subsequently, we estimated the benefits (life years gained (LYG)), burden (number of screening events, colonoscopies and false-positive tests), harms (number of colonoscopy complications) and costs (Renminb (¥)) of screening for 324 alternative screening strategies. We compared several different age ranges, screening modalities, intervals and FIT cut-off levels. An incremental cost-effectiveness analysis determined the optimal strategy assuming a willingness-to-pay of ¥193 931 per LYG.Results Compared with no screening, the current screening programme reduced CRC incidence by 40% (19 cases per 1000 screened individuals) and CRC mortality by 67% (7 deaths). This strategy gained 32 additional life years, increased colonoscopy demand to 1434 per 1000 individuals and cost an additional ¥199 652. The optimal screening strategy was annual testing using a validated one-sample FIT, with a cut-off of 10 µg haemoglobin per gram from ages 45 to 80 years (incremental cost-effectiveness ratio, ¥62 107). This strategy increased LY by 0.18% and costs by 27%. Several alternative cost-effective strategies using a validated FIT offered comparable benefits to the current programme but lower burden and costs.Conclusions Although the current screening programme in Shanghai is effective at reducing CRC incidence and mortality, the programme could be optimised using a validated FIT. When implementing CRC screening, jurisdictions with limited health resources should use a validated test.

Quantification of germination characteristics between herbicide-resistant and -susceptible weeds might provide methods to control resistant weeds and permit better prediction of evolution and persistence of herbicide resistance. This study aimed to compare the germination characteristics of Asian minor bluegrass (Polypogon fugax) populations that are resistant or susceptible to quizalofop-p-ethyl under controlled conditions, which the resistance mechanism is involved in glutathione S-transferases (GSTs) metabolism-based resistance. No major differences in seed germination were found at diverse temperatures, pH ranges, and light conditions. However, a significant difference that seed response to a gradient of osmotic and salt stress between the resistant and susceptible P. fugax populations were found. Two stress response genes (P5CS-1 and CDPK-2) in P. fugax were likely involved in germination rate as well as germination speed in response to these stresses. Subsequently, population verification demonstrated that P5CS-1 and CDPK-2 genes may be linked to the resistance mechanism. Additionally, the two genes play an important role in response to salt stress and osmotic stress as shown by transcript abundance after stress treatments. Our findings suggest that the variation of the germination characteristics in P. fugax associates with the presence of GST-endowed resistance mechanism.

Aim: The 20(S)-ginsenoside Rh2 (Rh2) is being developed as a new antitumor drug. However, to date, little is known about the kinetics of its deglycosylation metabolite (protopanoxadiol) (PPD) following Rh2 administration. The aim of this work was to 1) simultaneously characterise the pharmacokinetics of Rh2 and PPD following intravenous and oral Rh2 administration, 2) develop and validate a mechanism-based pharmacokinetic model to describe the deglycosylation kinetics and 3) predict the percentage of Rh2 entering the systemic circulation in PPD form.Methods: Plasma samples were collected from rats after the I.V. or P.O. administration of Rh2. The plasma Rh2 and PPD concentrations were determined using HPLC-MS. The transformation from Rh2 to PPD, its absorption, and elimination were integrated into the mechanism based pharmacokinetic model to describe the pharmacokinetics of Rh2 and PPD simultaneously at 10 mg/kg. The concentration data collected following a 20 mg/kg dose of Rh2 was used for model validation.Results: Following Rh2 administration, PPD exhibited high exposure and atypical double peaks. The model described the abnormal kinetics well and was further validated using external data. A total of 11% of the administered Rh2 was predicted to be transformed into PPD and enter the systemic circulation after I.V. administration, and a total of 20% of Rh2 was predicted to be absorbed into the systemic circulation in PPD form after P.O. administration of Rh2.Conclusion: The developed model provides a useful tool to quantitatively study the deglycosylation kinetics of Rh2 and thus, provides a valuable resource for future pharmacokinetic studies of glycosides with similar deglycosylation metabolism.

Abstract Tumor necrosis factor receptor (TNFR)-related factors (TRAFs) are important linker molecules in the tumor necrosis factor superfamily (TNFSF) and the Toll-like/interleukin-1 receptor (TLR/ILR) superfamily. There are seven members: TRAF1-TRAF7, among those members, tumor necrosis factor receptor-associated factor 6 (TRAF6) is upregulated in various tumors, which has been related to tumorigenesis and development. With the in-depth study of the relationship between TRAF6 and different types of tumors, TRAF6 has oncogenic characteristics involved in tumorigenesis, tumor development, invasion, and metastasis through various signaling pathways, therefore, targeting TRAF6 has provided a novel strategy for tumor treatment. This review summarizes and analyzes the role of TRAF6 in tumorigenesis and tumor development in combination with the current research on TRAF6 and tumors.

Abstract Background Spermatogonial stem cell (SSC) transplantation technology as a promising option for male fertility preservation has received increasing attention, along with efficient SSC purification technology as a necessary technical support; however, the safety of such application in patients with tumors remains controversial. Methods In this study, we used a green fluorescent protein mouse xenograft model of B cell acute lymphocytic leukemia. We isolated and purified SSCs from the testicular tissue of model mice using density gradient centrifugation, immune cell magnetic bead separation, and flow cytometry. The purified SSCs were transplanted into convoluted seminiferous tubules of the nude mice and C57BL/6 male mice subjected to busulfan. The development and proliferation of SSCs in the recipient testis were periodically tested, along with whether B cell acute lymphocytic leukemia was induced following SSC implantation. The genetic characteristics of the offspring obtained from natural mating were also observed. Results In testicular leukemia model mice, a large number of BALL cells infiltrated into the seminiferous tubule, spermatogenic cells, and sperm cells in the testis tissue decreased. After spermatogonial stem cell transplantation, the transplanted SSCs purified by immunomagnetic beads and flow cytometry methods colonized and proliferated extensively in the basement of the seminiferous tubules of mice; a large number of spermatogenic cells and sperm were found in recipient testicular tissue after 12 weeks of SSC transplantation. In leukemia detection in nude mice after transplantation in the three SSC purification groups, a large number of BALL cells could be detected in the blood of recipient mice 2–3 weeks after transplantation in the density gradient centrifugation group, but not in the blood of the flow cytometry sorting group and the immunomagnetic bead group after 16 weeks of observation. Conclusions In this study, we confirmed that immunomagnetic beads and flow cytometry methods of purifying SSCs from the testicular tissue of the testicular leukemia mouse model could be safely applied to the SSC transplantation technology without concomitant tumor implantation. The results thus provide a theoretical basis for the application of tumor SSC cryopreservation for fertility preservation in patients with tumors.

This article takes the Guangdong Province of China as the research object and uses the difference-in-difference model to evaluate the impact of smart city construction on the quality of public occupational health and intercity differences. The obtained results show that smart city construction significantly improves the quality of public occupational health, and it is still valid after a series of robustness tests. The effect of this policy is stronger in cities that belong to the Pearl River Delta region or sub-provincial level cities. This study indicates that the central government should improve the pilot evaluation system and the performance appraisal mechanism of smart cities from the perspective of top-level design during the process of promoting smart city construction, which aims to correctly guide local governments to promote the construction of smart cities. To achieve the full improvement effect of smart city construction on the quality of public occupational health, local governments should implement smart city strategies in a purposeful and planned way according to the actual situation of the development of the jurisdiction.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19.Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment.Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151).Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments.Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

The assembly quality between bearing components will lead to an increase in the load imbalance of each rolling element, which becomes a factor that affects the heat generation of precision bearings. The motion and heat generation of angular contact ball bearing (ACBB) under different assembly states were studied, and the quasi-static model of ACBB with outer ring tilting was established. The contact angle, contact load and motion posture of rolling elements were obtained. Then, the relative imbalance of the outer ring was experimentally simulated based on the outer spacer ring with poor end-parallelism, and the thermal characteristics of the spindle system were monitored. Through theoretical and experimental comparison, the influence of different skew degrees of rings on bearing heat generation and spindle rotation accuracy was discussed.

Interface states in photonic crystals (PCs) have attracted attention for the special properties, such as high transmission efficiency in bend waveguides, and their generation related to the topological phase. Previous works on interface states in PCs were mainly based on the square lattice, the honeycomb lattice or the triangular lattice, but with different materials, shapes, or sizes of rods resulting in the complicated structure. In this paper, an interface is constructed by two 2D PCs with different rectangular lattices, but the same materials, shapes, and sizes of dielectric rods, which generates interface states. The interface states are analyzed with respect to Zak phases and surface impedances. The retainability of the interface states in rectangular lattice PCs is investigated by studying the relationship between the length-width ratio of the rectangular lattice and the Zak phase. It is found that, when the interface states are generated by changing the length-width ratio of the rectangular lattice, the retainability of the interface states is related to the positions of the photonic bandgaps or the Zak phases of the bands. A more detailed examination indicates that these conclusions are applicable to the rectangular lattice PCs with other materials, shapes, and sizes of dielectric rods. These results can lead to new ways to generate interface states easily, with only one kind of dielectric rod. In addition, these outcomes may contribute to the understanding of the relationship between the geometry and the interface state.

Roton dispersion relations were firstly predicted by Landau and have been extensively explored in correlated quantum systems at low temperatures. Recently, the roton-like dispersion relations were theoretically extended to classical acoustics, which, however, have remained elusive in reality. Here, we report the experimental observation of roton-like dispersions in acoustic metamaterials with beyond-nearest-neighbour interactions at ambient temperatures. The resulting metamaterial supports multiple coexisting modes with different wavevectors and group velocities at the same frequency and broadband backward waves, analogous to the ‘return flow’ termed by Feynman in the context of rotons. By increasing the order of long-range interaction, we observe multiple rotons on a single dispersion band, which have never appeared in Landau’s prediction or any other condensed-matter or classical-wave studies. Moreover, we have also theoretically proposed and experimentally observed multidirectional roton-like dispersion relations in a two-dimensional nonlocal acoustic metamaterial. The realization of roton-like dispersions in metamaterials could pave the way to explore novel physics and applications on quantum-inspired phenomena in classical systems.

Abstract Background This study not only evaluated the clinical effects of treatment using haploidentical hematopoietic stem cells (haplo-HSCs) combined with human umbilical cord mesenchymal stem cells (UC-MSCs) in patients with severe aplastic anemia (SAA), but also investigated the factors related to graft versus host disease (GVHD). Methods Cotransplantation of haplo-HSCs and UC-MSCs was performed in 24 SAA patients. The conditioning regimens consisted of rabbit anti-human T-lymphocyte immunoglobulin (ATG), cyclophosphamide, and fludarabine with or without busulfan. GVHD was prevented using cyclosporine A, ATG, anti-CD25 monoclonal antibody, and mycophenolate material. Results The incidence of acute GVHD was 50%. The incidence of severe acute GVHD was not related to gender, age, donor-recipient relations, and patient/donor pair, while patient/donor pair (r = 0.541, P = 0.022) was significantly correlated with incidence of chronic GVHD. Upon follow-up for a median of 13 months, 5 of the 24 patients (20.8%) were dead. The survival rates at 3 and 6 months in all patients were 87.5% (21/24) and 83.3% (20/24), respectively. Conclusion Cotransplantation of haplo-HSCs combined with UC-MSCs was an effective and safe approach for the treatment of patients with SAA. The appropriate conditioning regimen and early treatment for infection also played a critical role in the success of HSCT.

Abstract Background Life expectancy at birth (LE) is a comprehensive measure that accounts for age-specific death rates in a population. Shanghai has ranked first in LE in China mainland for decades. Understanding the reasons behind its sustained gain in LE provides a good reflection of many other cities in China. The aim of this study is intended to explore temporal trend in age- and cause-specific gains in LE in Shanghai and the probable reasons lay behind. Methods Joinpoint regression was applied to evaluate temporal trend in LE and the long time span was then divided accordingly. Contributions to change in LE (1973–2015) were decomposed by age and cause at corresponding periods. Results LE in Shanghai could be divided into four phases ie., descent (1973–1976), recovery (1976–1998), rapid rise (1998–2004) and slow rise (2004–2015). The growing LE was mainly attributed to reductions in mortality from the elderly populations and chronic diseases such as cerebrovascular disease, chronic lower respiratory disease, and gastrointestinal cancers (stomach, liver and esophageal cancer). Conclusions The four-decade sustained gain in LE in Shanghai is due to the reductions in mortality from the elderly and chronic diseases such as cerebrovascular disease, chronic lower respiratory disease, and gastrointestinal cancers. Further growth momentum still comes from the elderly population.

Background: Parallel test of risk stratification and two-sample qualitative fecal immunochemical tests (FITs) are used to screen colorectal cancer (CRC) in Shanghai, China. This study was designed to identify an optimal initial screening modality based on available data.Methods: A total of 538,278 eligible residents participated in the program during the period of January 2013 to June 2017. Incident CRC was collected through program reporting system and by record linkage with the Shanghai Cancer Registry up to December 2017. Logistic regression model was applied to identify significant factors to calculate risk score for CRC. Cutoff points of risk score were determined based on Youden index and defined specificity. Sensitivity, specificity, and positive predictive values (PPVs) were computed to evaluate validity of assumed screening modalities.Results: A total of 446 CRC were screen-detected, and 777 interval or missed cases were identified through record linkage. The risk score system had an optimal cutoff point of 19 and performed better in detecting CRC and predicting long-term CRC risk than did the risk stratification. When using a cutoff point of 24, parallel test of risk score, and FIT were expected to avoid 56 interval CRCs with minimal decrease in PPV and increase in colonoscopy. However, the observed detection rates were much lower than those expected due to low compliance to colonoscopy.Conclusions: Risk score is superior to risk stratification used in the program, particularly when combined with FIT. Compliance to colonoscopy should be improved to guarantee the effectiveness of CRC screening in the population.

Introduction: Disparities in the incidence, mortality, and survival of cancer types between urban and rural areas in China reflect the effects of different risk factor exposure, education, and different medical availability. We aimed to characterize the disparities in the incidence, mortality, and survivals of cancer types between urban and rural areas in Shanghai, China, 2002-2015.Materials and Methods: The incidence and mortality were standardized by Segi's world standard population. Trends in the incidence and mortality of cancers were compared using annual percent change. The 5-year observed and relative survivals were calculated with life table and Ederer II methods.Results: Age-standardized incidences and mortalities were 212.55/105 and 109.45/105 in urban areas and 210.14/105 and 103.99/105 in rural areas, respectively. Female breast cancer and colorectal cancer occurred more frequently in urban than in rural areas, quite in contrast to liver cancer and cervical cancer. Cancers of lung and bronchus, liver, stomach, and colon and rectum were the leading causes of cancer death in both areas. Age-standardized incidence of female breast cancer and colorectal cancer in urban areas increased while gastric cancer and liver cancer decreased in both areas. Age-standardized mortalities of cancers of breast, esophagus, stomach, colon and rectum, liver, and lung and bronchus decreased in both areas. For all cancers combined, the 5-year observed and relative survivals of cancer patients were higher in urban than in rural areas. The 5-year observed and relative survivals of cancers of liver, pancreas, stomach, brain and central nervous system (CNS), and prostate were higher in urban than in rural areas. The 5-year observed and relative survivals of cervical cancer were higher in rural than in urban areas.Conclusions: Factors promoting female breast cancer and colorectal cancer in urban areas and liver cancer and cervical cancer in rural areas should be specifically intervened in cancer prophylaxis. Improved medical services can greatly prolong the survival of major cancers in rural areas.

The present study examined the association between residential indoor remodeling and poor semen quality. Sperm donors aged 18-45 years old were recruited in Shanghai, China. Semen specimens were collected and analyzed. An in-person interview was conducted to obtain information on the history of indoor remodeling and potential confounders. A total of 70 participants with abnormal semen quality (case group) and 68 controls were examined. A total of 20 subjects reported indoor remodeling in the recent 24 months, and among them 17 subjects reported indoor remodeling in the recent 12 months. Compared with participants with no history of indoor remodeling, participants with a history of indoor remodeling in the recent 24 months were more than three times as likely to have poor sperm quality (adjusted odds ratio = 3.8, 95% confidence interval: 1.3-12.0) after controlling for potential confounders. The association was strengthened when the analysis was restricted to those who had indoor remodeling in the recent 12 months. Our findings provide preliminary evidence that indoor remodeling has an adverse effect on semen quality.

Background and objective Different histologies of lung cancer vary in occurrence and prognosis. This study aims to analyze the incidence and occurrence trend of lung cancer and investigate the survival rate and its influential factors among lung cancer patients with different histologies. Methods Permanent residents were recruited between 2002 and 2009 in Pudong New Area (former Nanhui Area and former Pudong Area), Shanghai, China. Annual percent changes were estimated by a linear regression of the logarithm on the incidence rates for eight years. Survival rates were calculated and compared by using life-table analysis and Log-rank test, respectively. Results The standardized incidence rates of lung cancer were 52.28 and 18.86 per 100,000 in males and females, respectively. The median survival time was 410.72 days for specific classified lung cancer. The incidence rates of adenocarcinoma ranked the highest and showed an upward tendency (P

PURPOSE:To evaluate the association of social support status, health insurance and clinical factors with the quality of life of Chinese women with breast cancer. METHODS:Information on demographics, clinical characteristics, and social support status was collected from 1,160 women with newly diagnosed breast cancer in Shanghai, China. The Perceived Social Support Scale was used to assess different sources of social support for breast cancer patients. The quality of life was evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer that consisted of five domains: breast cancer-specific, emotional, functional, physical, and social & family well-being. Multivariate linear regression models were used to evaluate the associations of demographic variables, clinical characteristics, and social support status with the quality of life measures. RESULTS:Adequate social support from family members, friends and neighbors, and higher scores of Perceived Social Support Scale were associated with significantly improved quality of life of breast cancer patients. Higher household income, medical insurance plans with low copayment, and treatment with traditional Chinese medicine for breast cancer all were associated with higher (better) scores of quality of life measures whereas patients receiving chemotherapy had significantly lower scores of quality of life. CONCLUSION:Social support and financial aids may significantly improve the quality of life of breast cancer survivors.

For fuel transmission and structural strengthening, small-diameter pipes of nonmagnetic materials are extensively adopted in engineering fields including aerospace, energy, transportation, etc. However, the hostile and corrosive environment leaves them vulnerable to external corrosion which poses a severe threat to structural integrity of pipes. Therefore, it is imperative to nondestructively detect and evaluate the external corrosion in nonmagnetic pipes. In light of this, a capsule-type Electromagnetic Acoustic Transducer (EMAT) for in-situ nondestructive evaluation of nonmagnetic pipes and fast screening of external corrosion is proposed in this paper. A 3D hybrid model for efficient prediction of responses from the proposed transducer to external corrosion is established. Closed-form expressions of field quantities of electromagnetics and EMAT signals are formulated. Simulations based on the hybrid model indicate feasibility of the proposed transducer in detection and evaluation of external corrosion in nonmagnetic pipes. In parallel, experiments with the fabricated transducer have been carried out. Experimental results are supportive of the conclusion drawn from simulations. The investigation via simulations and experiments implies that the proposed capsule-type EMAT is capable of fast screening of external corrosion, which is beneficial to the in-situ nondestructive evaluation of small-diameter nonmagnetic pipes.

A corrosive environment leaves in-service conductive structures prone to subsurface corrosion which poses a severe threat to the structural integrity. It is indispensable to detect and quantitatively evaluate subsurface corrosion via non-destructive evaluation techniques. Although the gradient-field pulsed eddy current technique (GPEC) has been found to be superior in the evaluation of corrosion in conductors, it suffers from a technical drawback resulting from the non-uniform field excited by the conventional pancake coil. In light of this, a new GPEC probe with uniform field excitation for the imaging of subsurface corrosion is proposed in this paper. The excited uniform field makes the GPEC signal correspond only to the field perturbation due to the presence of subsurface corrosion, which benefits the corrosion profiling and sizing. A 3D analytical model of GPEC is established to analyze the characteristics of the uniform field induced within a conductor. Following this, experiments regarding the imaging of subsurface corrosion via GPEC have been carried out. It has been found from the results that the proposed GPEC probe with uniform field excitation not only applies to the imaging of subsurface corrosion in conductive structures, but provides high-sensitivity imaging results regarding the corrosion profile and opening size.

Coated conductive structures are widely adopted in such engineering fields as aerospace, nuclear energy, etc. The hostile and corrosive environment leaves in-service coated conductive structures vulnerable to Hidden Material Degradation (HMD) occurring under the protection coating. It is highly demanded that HMD can be non-intrusively assessed using non-destructive evaluation techniques. In light of the advantages of Gradient-field Pulsed Eddy Current technique (GPEC) over other non-destructive evaluation methods in corrosion evaluation, in this paper the GPEC probe for quantitative evaluation of HMD is intensively investigated. Closed-form expressions of GPEC responses to HMD are formulated via analytical modeling. The Lift-off Invariance (LOI) in GPEC signals, which makes the HMD evaluation immune to the variation in thickness of the protection coating, is introduced and analyzed through simulations involving HMD with variable depths and conductivities. A fast inverse method employing magnitude and time of the LOI point in GPEC signals for simultaneously evaluating the conductivity and thickness of HMD region is proposed, and subsequently verified by finite element modeling and experiments. It has been found from the results that along with the proposed inverse method the GPEC probe is applicable to evaluation of HMD in coated conductive structures without much loss in accuracy.

We examined if transplantation of combined haploidentical hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) affected graft failure and graft-versus-host disease (GVHD) in patients with severe aplastic anemia (SAA). Patients with SAA-I (N = 17) received haploidentical HSCT plus MSC infusion. Stem cell grafts used a combination of granulocyte colony-stimulating factor (G-CSF)-primed bone marrow and G-CSF-mobilized peripheral blood stem cells of haploidentical donors and the culture-expanded third-party donor-derived umbilical cord MSCs (UC-MSCs), respectively. Reduced intensity conditioning consisted of fludarabine (30 mg/m2·d)+cyclosphamide (500 mg/m2·d)+anti-human thymocyte IgG. Transplant recipients also received cyclosporin A, mycophenolatemofetil, and CD25 monoclonal antibody. A total of 16 patients achieved hematopoietic reconstitution. The median mononuclear cell and CD34 count was 9.3×10(8)/kg and 4.5×10(6)/kg. Median time to ANC was >0.5×10(9)/L and PLT count >20×10(9)/L were 12 and 14 days, respectively. Grade III-IV acute GVHD was seen in 23.5% of the cases, while moderate and severe chronic GVHD were seen in 14.2% of the cases. The 3-month and 6-month survival rates for all patients were 88.2% and 76.5%, respectively; mean survival time was 56.5 months. Combined transplantation of haploidentical HSCs and MSCs on SAA without an HLA-identical sibling donor was safe, effectively reduced the incidence of severe GVHD, and improved patient survival.

The BCR-ABL tyrosine kinase inhibitor imatinib is highly effective for chronic myeloid leukemia (CML). However, some patients gradually develop resistance to imatinib, resulting in therapeutic failure. Metabonomic and genomic profiling of patients' responses to drug interventions can provide novel information about the in vivo metabolism of low-molecular-weight compounds and extend our insight into the mechanism of drug resistance. Based on a multi-platform of high-throughput metabonomics, SNP array analysis, karyotype and mutation, the metabolic phenotypes and genomic polymorphisms of CML patients and their diverse responses to imatinib were characterized. The untreated CML patients (UCML) showed different metabolic patterns from those of healthy controls, and the discriminatory metabolites suggested the perturbed metabolism of the urea cycle, tricarboxylic acid cycle, lipid metabolism, and amino acid turnover in UCML. After imatinib treatment, patients sensitive to imatinib (SCML) and patients resistant to imatinib (RCML) had similar metabolic phenotypes to those of healthy controls and UCML, respectively. SCML showed a significant metabolic response to imatinib, with marked restoration of the perturbed metabolism. Most of the metabolites characterizing CML were adjusted to normal levels, including the intermediates of the urea cycle and tricarboxylic acid cycle (TCA). In contrast, neither cytogenetic nor metabonomic analysis indicated any positive response to imatinib in RCML. We report for the first time the associated genetic and metabonomic responses of CML patients to imatinib and show that the perturbed in vivo metabolism of UCML is independent of imatinib treatment in resistant patients. Thus, metabonomics can potentially characterize patients' sensitivity or resistance to drug intervention.