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This code is related to a bead-spring model for a fiber with spontaneous curvature written in Python. (https://github.com/Jian-S/Bead-spring-model) For more details, please refer to our paper "Active Laminated-Plate Model for Spontaneous Bending of Hydra Tissue Fragments Driven by Supracellular Actomyosin Bundles", whose link isCommun Phys6, 185 (2023).https://doi.org/10.1038/s42005-023-01307-9. To run this script, please install Jupyter first.

Variational methods have been widely used in soft matter physics for both static and dynamic problems. These methods are mostly based on two variational principles: the variational principle of minimum free energy (MFEVP) and Onsager's variational principle (OVP). Our interests lie in the applications of these variational methods to active matter physics. In our former work [Soft Matter, 2021, 17, 3634], we have explored the applications of OVP-based variational methods for the modeling of active matter dynamics. In the present work, we explore variational (or energy) methods that are based on MFEVP for static problems in active elastic solids. We show that MFEVP can be used not only to derive equilibrium equations, but also to develop approximate solution methods, such as Ritz method, for active solid statics. Moreover, the power of Ritz-type method can be further enhanced using deep learning methods if we use deep neural networks to construct the trial solutions of the variational problems. We then apply these variational methods and the deep Ritz method to study the spontaneous bending and contraction of a thin active circular plate that is induced by internal asymmetric active contraction. The circular plate is found to be bent towards its contracting side. The study of such a simple toy system gives implications for understanding the morphogenesis of solid-like confluent cell monolayers. In addition, we introduce a so-called activogravity length to characterize the importance of gravitational forces relative to internal active contraction in driving the bending of the active plate. When the lateral plate dimension is larger than the activogravity length (about 100 micron), gravitational forces become important. Such gravitaxis behaviors at multicellular scales may play significant roles in the morphogenesis and in the up-down symmetry broken during tissue development., 19 pages, 8 figures

Cell-scale curvature plays important roles in controlling cell and tissue behaviors. However, these roles have not been well quantified, and the underlying mechanisms remain elusive. We combine experiments with theory to study systematically the curvature-dependence of cell migration inside PDMS microcylinders. We find that persistence is positively correlated with speed, following the universal speed-persistence coupling relation,i.e., faster cells turn less. Cell migration inside microcylinders is anisotropic and depends on curvature in a biphasic manner. At small curvatures, as curvature increases, the average speed and anisotropy both increase, but surprisingly, the average persistence decreases. Whereas as the curvature increases over some threshold, cells detach from the surface, the average speed and anisotropy both decrease sharply but the average persistence increases. Moreover, interestingly, cells are found to leave paxillins along their trajectories (on curved but not planar surfaces), facilitating the assembly of focal adhesions of following cells. We propose a minimal model for the biphasic curvotaxis based on three mechanisms: the persistent random “noise”, the bending penalty of stress fibers, and the cell-surface adhesion. The findings provide a novel and general perspective on directed cell migration in the widely existing curved microenvironment of cellsin vivo.

We report a systematic study of the dynamics of self-propelled particles (SPPs) over a one-dimensional periodic potential landscape, which is fabricated on a microgroove-patterned polydimethylsiloxane (PDMS) substrate. From the measured non-equilibrium probability density function of the SPPs, we find that the escape dynamics of the slow-rotating SPPs across the potential landscape can be described by an effective potential, once the self-propulsion force is included into the potential under the fixed angle approximation. This work demonstrates that the parallel microgrooves provide a versatile platform for a quantitative understanding of the interplay among the self-propulsion force, spatial confinement by the potential landscape, and thermal noise, as well as its effects on activity-assisted escape dynamics and transport of the SPPs.

ObjectivesTo evaluate the benefit distribution of social health insurance among domestic migrants in China.DesignA national cross-sectional survey.Setting348 cities from 32 provincial units in China.Participants1165 domestic migrants who used inpatient care services in the city of a new residence and had social health insurance.Primary and secondary outcome measuresThe probability of receiving reimbursements from social health insurance, the amounts and ratio of reimbursement received.ResultsAmong migrants who used inpatient care in 2013, only 67% received reimbursements from social health insurance, and the reimbursement amount only accounted for 47% of the inpatient care expenditure. The broader the geographical scope of migration, the lower the probability of receiving reimbursement and the reimbursement ratio, but the higher the reimbursement amount. Specifically, the probability of receiving reimbursements for those who migrated across cities or provinces was significantly lower by 14.7% or 26.0%, respectively, than those who migrated within a city. However, they received significantly higher reimbursement amounts by 33.4% or 27.2%, respectively, than those who migrated within a city. And those who migrated across provinces had the lowest reimbursement ratio, although not reaching significance level.ConclusionsThe unequal benefit distribution among domestic migrants may be attributed to the fragmented health insurance design that relies on localised administration, and later reimbursement approach that migrating patients pay for health services up-front and get reimbursement later from health insurance. To improve the equity in social health insurance benefits, China has been promoting the portability of social health insurance, immediate reimbursement for inpatient care used across regions, and a more integrated health insurance system. Efforts should also be made to control inflation of healthcare expenditures and prevent inverse government subsidies from out-migration regions to in-migration regions. This study has policy implications for China and other low/middle-income countries that experience rapid urbanisation and domestic migration.

Background Childhood overweight and obesity (OWO) has become a major public concern worldwide including in Shanghai, one of the most developed areas of China. Understanding perceptions and challenges of tackling childhood OWO among caregivers of children is critical to provide services in need. Methods A qualitative descriptive study including in-depth interviews with seven parents and six focus group discussions with a total of 32 parents or grandparents of children zero to 6 years of age. Participants lived in three districts of Shanghai and indexed children included both those with OWO or non-OWO children. Data were analyzed using qualitative thematic analysis. Results Caregivers tended to underestimate children’s weight status, and to regard chubby children as a sign of good parental care. Some caregivers even suggested that there were positive effects of childhood overweight. Caregivers identified a number of challenges to prevention of OWO in children, including difficulties in controlling dietary intake or increasing children’s physical activities; discordant views between parents and grandparents, and barriers to accessing professional guidance. Caregivers desired more detailed advice regarding children’s nutrition intake and physical activity, and preferred online approaches. Conclusions Misconceptions regarding childhood overweight were found in caregivers of children in Shanghai. Professional guidance on childhood weight control for caregivers is desired via digital applications such as mobile phone applications and social media.

Xue Lian,1,2 Dakui Cao,2 Xun Hu,3 Weiqiang Mo,2 Xiujuan Yao,4 Juanfen Mo,5 Haiqin Wang1,2 1Department of Respiratory Medicine, Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Respiratory Medicine, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 3Department of Thoracic Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 4Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of China; 5The Key Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, People’s Republic of ChinaCorrespondence: Haiqin Wang, Department of Respiratory Medicine, The Second Hospital of Jiaxing, 1518 Huanchen North Road, Jiaxing, Zhejiang, 314000, People’s Republic of China, Email w_haiqin@163.comBackground: Lung adenocarcinoma (LUAD) is a life-threatening disease worldwide with a high mortality rate. The early diagnosis of LUAD is crucial for improving subsequent treatment and prognosis. However, biomarkers for early detection remain a clinical challenge in LUAD. Here, we aimed to develop circular RNAs (circRNAs) in circulating plasma from LUAD patients as valuable diagnostic biomarkers in LUAD.Methods: CircRNA expression was determined by circRNA microarray in three pairs of LUAD tumour tissues and patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were selected as potential biomarkers in LUAD tissues and plasma by RT–PCR, respectively. The diagnostic value was analysed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test.Results: Our results showed that 6261 circRNAs were upregulated and 7238 circRNAs were downregulated in LUAD tumour tissues compared with patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were filtered as biomarkers for early-stage LUAD. Q-PCR results showed that hsa_circ_101555 and hsa_circ_008068 were significantly upregulated in both LUAD cancer tissues and circulating plasma. Hsa_circ_101555 and hsa_circ_008068 were positively associated with tumour differentiation, tumour size and CEA (P< 0.05). The ROC analysis showed that hsa_circ_101555 and hsa_circ_008068 had a better diagnostic potential compared to the traditional biomarkers (CEA, SCC, CYFRA21-1) in the detection of early-stage LUAD.Conclusion: The circular RNAs hsa_circ_101555 and hsa_circ_008068 could serve as novel diagnostic biomarkers for early-stage LUAD.Keywords: circRNAs, lung adenocarcinoma, diagnostic biomarker, circ101555

Hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome is a life-threatening pregnancy complication. Though there are several medications widely used to treat HELLP syndrome, delivery is the only efficient treatment. The goal of the present study was to investigate the effects of platelet-derived growth factor-D (PDGF-D), a newly identified PDGF, in a rat model of HELLP syndrome which was accomplished by sFlt-1 and sEng injection. The expression levels of PDGF-D in pregnant women diagnosed with HELLP syndrome was determined. A HELLP rat model was established and the PDGF-D expression level in the plasma and the placenta tissue was evaluated. To evaluate the effects of PDGF-D in HELLP syndrome model, siPDGF-D was injected into the rats and the HELLP syndrome-related parameters were measured. The levels of inflammatory cytokines and PDGF-D were determined by ELISA. The oxidative stress activities in the plasma were also determined. Furthermore, the expression of PDGF-D/PDGFR-β/nuclear factor κB (NF-κB) p65 in placenta tissues was evaluated by Western blotting. Compared to the normal pregnant (NP) group, the levels of PDGF-D were augmented regardless of species. Knockdown of PDGF-D can result in the alleviation of HELLP syndrome development and progression in the HELLP rat model. Importantly, as a result of PDGF-D knockdown, the serum levels of inflammatory cytokines and oxidative stress activities were modulated, and the phosphorylation of PDGFR-β and NF-κB p65 in placenta tissue was inhibited. Taking together, our findings indicate that targeting PDGF-D could be used as a novel strategy to treat patients with HELLP syndrome.

Two-dimensional electrophoresis (2-DE) and MALDI-TOF/TOF mass spectrometry were performed to compare the proteomic alterations of lycorine-treated and control cells to further investigate the anti-multiple myeloma (MM) mechanisms of lycorine. Mass spectrometry results showed that after lycorine treatment of MM cells, 42% of the differentially expressed proteins had subcellular localization, mainly, on mitochondria. Voltage-dependent anion-selective channel protein 2 (VDAC2), the most abundant protein in the outer mitochondrial membrane, was up-regulated after treatment with lycorine and was subsequently verified by western blot analysis. Further studies on mitochondria found that lycorine was able to increase abnormal mitochondria and increase mitochondrial membrane potential. Lycorine can achieve the effect of resisting multiple myeloma by acting on VDAC2 and causing mitochondrial abnormalities.

Propylparaben (PrP) is a widely used preservative that is constantly detected in aquatic environments and poses a potential threat to aquatic ecosystems. In the present work, adult male mosquitofish were acutely (4d) and chronically (32d) exposed to environmentally and humanly realistic concentrations of PrP (0, 0.15, 6.00 and 240 μg/L), aimed to investigate the toxic effects, endocrine disruption and possible mechanisms of PrP. Histological analysis showed time- and dose-dependent manners in the morphological injuries of brain, liver and testes. Histopathological alterations in the liver were found in 4d and severe damage was identified in 32d, including hepatic sinus dilatation, cytoplasmic vacuolation, cytolysis and nuclear aggregation. Tissue impairments in the brain and testes were detected in 32d; cell cavitation, cytomorphosis and blurred cell boundaries appeared in the brain, while the testes lesions contained spermatogenic cell lesion, decreased mature seminal vesicle, sperm cells gathering, seminiferous tubules disorder and dilated intercellular space. Furthermore, delayed spermatogenesis had occurred. The transcriptional changes of 19 genes along the hypothalamus–pituitary–gonadal–liver (HPGL) axis were investigated across the three organs. The disrupted expression of genes such as Ers, Ars, Vtgs, cyp19a, star, hsd3b, hsd17b3 and shh indicated the possible abnormal steroidogenesis, estrogenic or antiandrogen effects of PrP. Overall, the present results provided evidences for the toxigenicity and endocrine disruptive effects on the male mosquitofish of chronic PrP exposure, which highlights the need for more investigations of its potential health risks.

Multiple myeloma (MM) is an incurable condition and the second most common hematological malignancy. Over the past few years, there has been progress in the treatment of MM, but most patients still relapse. Multiple myeloma stem-like cells (MMSCs) are believed to be the main reason for drug resistance and eventual relapse. Currently, there are not enough therapeutic agents that have been identified for eradication of MMSCs, and thus, identification of the same may alleviate the issue of relapse in patients. In the present study, we showed that luteolin (LUT), a natural compound obtained from different plants, such as vegetables, medicinal herbs, and fruits, effectively inhibits the proliferation of MM cells and overcomes bortezomib (BTZ) resistance in them in vitro and in vivo, mainly by decreasing the proportion of ALDH1

Multiple myeloma is a plasma cell malignancy, accounting for approximately 1% of new cancer cases. It is the second most common hematological malignancy. Novel clinical agents such as the proteasome inhibitor-bortezomib, have shown improved survival rates in recent decades. However, multiple myeloma remains incurable, as most patients eventually relapse and become refractory to current treatments. Therefore, there is an urgent need for developing new regimens to overcome the bortezomib resistance. Here, we screened a library of 2370 bioactives and found that polyphyllin VII selectively suppressed multiple myeloma cell growth in vitro and in vivo. We identified moesin, one of the critical regulators of the Wnt/β-catenin pathway, as a target of polyphyllin VII by drug affinity responsive target stability assay and cellular thermal shift assay. Polyphyllin VII binds to moesin and induces its degradation via the ubiquitin-proteasome pathway, thereby impairing the Wnt/β-catenin pathway activity and leading to a reduction in the side population cells to overcome bortezomib resistance. Our study identified polyphyllin VII as a promising compound and moesin as a potential diagnostic and therapeutic target for treating multiple myeloma.

CO2 enhanced oil recovery (CO2-EOR) has been widely used in oil field exploitation in recent years. The injections of CO2 and ethane are easy to form an azeotrope, which makes difficult recovery of...

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138+ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138+ cells by decreasing ALDH1+ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1+ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.

Despite the establishment of novel therapeutic interventions, multiple myeloma (MM) remains invariably incurable due to development of drug resistance and subsequent relapse, which are attributed to activation of oncogenic pathways such as autophagy. Deubiquitinating enzymes (DUBs) are promising targets to overcome resistance to proteasome inhibitor-based treatment. Ubiquitin-specific protease-12 (USP12) is a DUB with a known prognostic value in several cancers. We found that USP12 protein levels were significantly higher in myeloma patient samples than in non-cancerous human samples. Depletion of USP12 suppressed cell growth and clonogenicity and inhibited autophagy. Mechanistic studies showed that USP12 interacted with, deubiquitylated and stabilized the critical autophagy mediator HMGB1 (high mobility group box-1) protein. Knockdown of USP12 decreased the level of HMGB1 and suppressed HMGB1-mediated autophagy in MM. Furthermore, basal autophagy activity associated with USP12/HMGB1 was elevated in bortezomib (BTZ)-resistant MM cell lines. USP12 depletion, concomitant with a reduced expression of HMGB1, suppressed autophagy and increased the sensitivity of resistant cells to BTZ. Collectively, our findings have identified an important role of the deubiquitylase USP12 in pro-survival autophagy and resultant BTZ resistance in MM by stabilizing HMGB1, suggesting that the USP12/HMGB1 axis might be pursued as a potential diagnostic and therapeutic target in human MM.

Background: Universal coverage through social health insurance is promoted by many researchers and policymakers to improve health equity within a country or region. In China, the mass internal migration since 1980s has posed challenges for the social health insurance to ensure equitable benefits for migrant population. This study evaluated the benefit distribution of social health insurance among internal migrants in China.Methods: Using the 2014 China National Internal Migrants Dynamic Monitoring Survey, , by applying a two-part model, we conducted a benefit analysis of social health insurance among a representative sample of migrants in China.Results: The study found that the broader the geographic scope of migration, the lower the probability of receiving reimbursements from the social health insurance and the reimbursement ratio; but among those who received reimbursements, the broader the geographic scope of migration, the larger amounts they were reimbursed for health care use. We attributed this unequal benefit distribution to the current insurance design that replies on localized administration and patients paying services up-front and requesting reimbursement later.Conclusion: To improve the equity in social insurance benefits between migrants and non-migrants and among migrants, policies that promote the insurance portability across regions and immediate reimbursement are warranted, while at the same time efforts should be done to control inflation of health care expenditures and to prevent inverse government subsidies from the regions that have more out-migration to regions that have in-migration.

Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1+ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.

Onsager's variational principle (OVP) was originally proposed by Lars Onsager in 1931 [L. Onsager, $Phys. Rev.$, 1931, $37$, 405]. This fundamental principle provides a very powerful tool for formulating thermodynamically consistent models. It can also be employed to find approximate solutions, especially in the study of soft matter dynamics. In this work, OVP is extended and applied to the dynamic modeling of active soft matter such as suspensions of bacteria and aggregates of animal cells. We first extend the general formulation of OVP to active matter dynamics where active forces are included as external non-conservative forces. We then use OVP to analyze the directional motion of individual active units: a molecular motor walking on a stiff biofilament and a toy two-sphere microswimmer. Next, we use OVP to formulate a diffuse-interface model for an active polar droplet on a solid substrate. In addition to the generalized hydrodynamic equations for active polar fluids in the bulk region, we have also derived thermodynamically consistent boundary conditions. Finally, we consider the dynamics of a thin active polar droplet under the lubrication approximation. We use OVP to derive a generalized thin film equation and then employ OVP as an approximation tool to find the spreading laws for the thin active polar droplet. By incorporating the activity of biological systems into OVP, we develop a general approach to construct thermodynamically consistent models for better understanding the emergent behaviors of individual animal cells and cell aggregates or tissues.

In this paper, the sensitivity analysis of Kiewitt-Lamella (K-L) reticulated domes with different parameters is carried out. The sensitivity of the dome due to gradual and sudden member loss is analyzed in both static and dynamic aspects, which will clarify the distribution rule of the member sensitivity and provide a reference for future study on the K-L reticulated dome. The results show that the member sensitivity of the K-L reticulated dome with different design parameters has similar regularities. For the members in the same ring, the sensitivity of the latitudinal members is larger than that of the diagonal members. For the members in different rings, the sensitivity of the inner ring members is larger than that of the outer ring members. In addition, the static analysis shows that the latitudinal members closer to the radial members are more sensitive than those apart from the radial members, and the diagonal members paralleling to the radial members are more sensitive than the unparallel ones. The dynamic analysis shows that the K-L reticulated dome will experience a local internal force redistribution after a member's sudden loss and finally reach a stable equilibrium state on the new load transfer path without overall progressive collapse. According to the research results, a better scheme for strengthening the structure is proposed: increasing the cross-section of sensitive members is more effective in improving the structural stability than important components.

With the complexity of supply chain network structure and the globalization of supply chain development, information sharing in supply chain becomes more and more important. Supply chain information sharing can not only improve the overall performance of the supply chain, promote cooperation and communication between supply chain nodes, reduce the “bullwhip effect” caused by information non-sharing, but also improve the response speed of supply chain to customer demand, which is conducive to the formation of core competitiveness of enterprises. With the arrival of the era of big data, information sharing has new opportunities and corresponding challenges in supply chain: on the one hand, the development of new technologies such as cloud computing and big data analysis technology has provided new sharing modes and channels for information sharing in supply chain; on the other hand, most of them have to face challenges. According to the storage and processing of massive information caused by massive data in the environment, new challenges are posed to enterprises. Based on the change of information sharing in supply chain under big data environment, it is very important to build a new information sharing mode. Based on the analysis of the advantages and disadvantages of three traditional information sharing modes, this paper constructs an identity-based and role-based information sharing mode using advanced storage platform and data prediction and mining methods in large data environment, which solves the problem of limited data storage and operation speed.

Factory environmental issues have always been the focus of attention, the factory is a highly populated place, the health and safety of workers is very important. The dust in the air can cause respiratory diseases, and the factory exhaust gas is a serious hazard to human health and can easily lead to fires. Based on the above problems, this paper designs a factory environment monitoring system based on Internet of Things, the design of the system uses 4G wireless communication technology, sensor technology, image acquisition technology, MySQL database design technology, dynamic web page development technology, WeChat public number development and other key technologies. The system can monitor a variety of environmental indicators in the factory and has good practical value.