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Abstract Coronary artery disease (CAD) is a predominant cardiovascular condition influenced by risk factors, with an emphasis on major depressive disorder (MDD). However, the shared mechanisms and therapeutic targets for CAD and MDD remain incompletely comprehended. Functional enrichment analyses were conducted to investigate the pathways associated with the differentially expressed genes (DEGs) in the CAD and MDD datasets. Hub genes were identified utilizing the Protein-Protein Interaction network and Cytoscape software. The single sample gene set variation analysis was applied to assess immune cell infiltration in the CAD and MDD datasets. Weighted gene co-expression network analysis and molecular biological experiments were executed to evaluate these hub genes. Molecular docking was conducted to identify drug candidates targeting these hub genes. The overlapping DEGs between the CAD and MDD datasets were mainly enriched in the Herpes simplex virus 1 infection and the NF-kappa B signaling pathways. CDC42, NDUFB3, and TXN were validated within the eigengenes of the blue module, which exhibited a significant association with the CAD phenotype. The drug candidate GS-9620 was identified as a potential protective agent against both disorders. In conclusion, CDC42, NDUFB3, and TXN held potential as molecular biomarkers and therapeutic targets for the simultaneous treatment of CAD and MDD.

Abstract Microswimmers are considered promising candidates for active cargo delivery to benefit a wide spectrum of biomedical applications. Yet, big challenges still remain in designing the microswimmers with effective propelling, desirable loading and adaptive releasing abilities all in one. Inspired by the morphology and biofunction of spermatozoa, we report a one-step formation strategy of polymorphous sperm-like magnetic microswimmers (PSMs) by developing a vortex turbulence-assisted microfluidics (VTAM) platform. The fabricated PSM is biodegradable with a core-shell head and flexible tail, and their morphology can be adjusted by vortex flow rotation speed and calcium chloride solution concentration. Benefiting from the sperm-like design, our PSM exhibits both effective motion ability under remote mag/netic actuation and protective encapsulation ability for material loading. Further, it can also realize the stable sustain release after alginate-chitosan-alginate (ACA) layer coating modification. This research proposes and verifies a new strategy for the sperm-like microswimmer construction, offering an alternative solution for the target delivery of diverse drugs and biologics for future biomedical treatment. Moreover, the proposed VTAM could also be a general method for other sophisticated polymorphous structures fabrication that isn’t achievable by conventional laminar flow.

Abstract Counterfeiting has become a serious global problem, causing worldwide losses and disrupting the normal order of society. Physical unclonable functions are promising hardware-based cryptographic primitives, especially those generated by chemical processes showing a massive challenge-response pair space. However, current chemical-based physical unclonable function devices typically require complex fabrication processes or sophisticated characterization methods with only binary (bit) keys, limiting their practical applications and security properties. Here, we report a flexible laser printing method to synthesize unclonable electronics with high randomness, uniqueness, and repeatability. Hexadecimal resistive keys and binary optical keys can be obtained by the challenge with an ohmmeter and an optical microscope. These readout methods not only make the identification process available to general end users without professional expertise, but also guarantee device complexity and data capacity. An adopted open-source deep learning model guarantees precise identification with high reliability. The electrodes and connection wires are directly printed during laser writing, which allows electronics with different structures to be realized through free design. Meanwhile, the electronics exhibit excellent mechanical and thermal stability. The high physical unclonable function performance and the widely accessible readout methods, together with the flexibility and stability, make this synthesis strategy extremely attractive for practical applications.

The unique motion styles of flagella and cilia (i.e., planar/helical waveform propulsion of flagella and two-dimensional (2D)/three-dimensional (3D) asymmetric ciliary beating), play a key role in many biological activities and inspire lots of bionic designs, especially miniature robotic systems. However, quite different to the fact in nature that microorganisms can evolve diverse motions from the homologous bio-structure (9 + 2 axoneme structure), current bionics can still not find an effective engineering solution to achieve such wisdom. Herein, by investigating the inner structure of flagella/cilia and their intrinsic driven mechanisms, we derive a unified physical model to describe the microtubules’ bending and the constructed external motions. Then, we propose a three-channel based tubular actuation concept and correspondingly fabricate an actuator via a rod-embedded casting process. By sequencing the actuation of each channel, our design can not only reproduce the diverse 2D/3D flagellar/ciliary motility in nature, but also extrapolate a variety of symmetry-breaking ciliary beating modes for effective propulsion at low Reynolds number. This study deepens our understanding of the propulsion mechanism of microorganisms and provides new inspirations for the design of biomimetic systems, which may find significant applications in a wide spectrum of engineering fields.

IntroductionThe parent–child attachment has a significant impact on adolescents’ mental health. However, the influence of psychological quality and coping styles on this connection remains unknown. This study examined the relationship between parent–child attachment and adolescent mental health, by exploring the mediating role of psychological quality and the moderating role of coping styles.MethodsA total of 633 young adolescents participated in this study after signing informed consent. They anonymously completed questionnaires including the Parent and Peer Attachment Scale (Parent Attachment Section), the Coping Styles Inventory for Middle School Students, the Brief Version of the Psychological Quality Inventory for Middle School Students, and the Chinese Middle School Students’Psychological Quality Inventory. After controlling for gender, grade, left-behind category, only-child status, and family structure.ResultsThe moderated mediation model yielded the following findings: (a) parent–child attachment significantly and positively predicted adolescents’mental health; (b) psychological quality partially mediated the relationship between parent–child attachment and adolescents’ mental health; (c) the association between psychological quality and mental health was moderated by task-focused coping.DiscussionThis moderation effect was more substantial for students with low task-focused coping behaviors, which aligns with the “exclusionary hypothesis” model. Therefore, our results indicate that parent–child attachment indirectly impacts mental health, influenced by internal and external factors. These findings carry significant implications for safeguarding and promoting adolescents’ mental well-being.

ABSTRACTDysregulation of the gut microbiota by environmental factors is associated with a variety of autoimmune and immune-mediated diseases. In addition, naturally-occurring extracellular antibiotic resistance genes (eARGs) might directly enter the gut via the food chain. However, following gut microbiota exposure to eARGs, the ecological processes shaping the microbiota community assembly, as well as the interplay between the microbiota composition, metabolic function, and the immune responses, are not well understood. Increasing focus on the One Health approach has led to an urgent need to investigate the direct health damage caused by eARGs. Herein, we reveal the significant influence of eARGs on microbiota communities, strongly driven by stochastic processes. How eARGs-stimulate variations in the composition and metabolomic function of the gut microbiota led to cytokine responses in mice of different age and sex were investigated. The results revealed that cytokines were significantly associated with immunomodulatory microbes, metabolites, and ARGs biomarkers. Cytokine production was associated with specific metabolic pathways (arachidonic acid and tryptophan metabolic pathways), as confirmed by ex vivo cytokine responses and recovery experiments in vivo. Furthermore, the gut microbial profile could be applied to accurately predict the degree of intestinal inflammation ascribed to the eARGs (area under the curve = 0.9616). The present study provided a comprehensive understanding of the influence of an eARGs on immune responses and intestinal barrier damage, shedding light on the interplay between eARGs, microbial, metabolites, and the gut antibiotic resistome in modulating the human immune system.

Purpose To compare the efficacy and safety of focused ultrasound (FUS) therapy and cryotherapy for cervical squamous intraepithelial lesion (SIL).Methods In this retrospective study, data pertaining to women treated for cervical SIL with FUS therapy or cryotherapy at the Second Affiliated Hospital of Chongqing Medical University between 21 April 2018 and 31 August 2020 were obtained. The patients were followed up after 3–6 and 6–12 months. The proportions of women with no evidence of disease, recurrent disease, clearance of the human papillomavirus (HPV) and adverse effects or complications were determined.Results Of the 250 women with complete data who were included in the study, 144 and 106 received FUS therapy and cryotherapy, respectively. Overall, FUS therapy was observed to be more effective than cryotherapy (91.7 vs. 79.2%, p = 0.005). Statistically significant differences were noted in the treatment efficacy for patients with low-grade SIL (LSIL) (92.3 vs. 80.2%, p = 0.011). However, there were no significant differences in the treatment efficacy for patients with high-grade SIL (HSIL) (88.9 vs. 75.0%, p = 0.390). The recurrence rates in patients with LSIL treated with FUS therapy or cryotherapy showed no significant differences at the 6–12-month follow-up (1.0 vs. 6.0%, p = 0.163). Furthermore, there was no recurrence in patients with HSIL, either in the FUS or cryotherapy group. FUS therapy and cryotherapy resulted in similar HPV clearance at the 3–6-month follow-up (77.1 vs. 64.8%, p = 0.057). No statistically significant differences were observed in the complication rates between the two groups (3.5 vs. 1.9%, p = 0.717).Conclusion The results of this study suggest that FUS therapy is superior to cryotherapy in the treatment of cervical LSIL.

Modular robots with reconfigurable architectures show advantages in unpredicted environments. Here Yang et al. propose a heterogeneous assembly concept for cellular robot construction at millimeter scales, which can simultaneously reconfigure their morphologies and behaviours to conduct versatile tasks on demand.

Diet can not only provide nutrition for intestinal microbiota, it can also remodel them. However, is unclear whether and how diet affects the spread of antibiotic resistance genes (ARGs) in the intestinal microbiota. Therefore, we employed selected high-sugar, high-fat, high-protein, and normal diets to explore the effect. The results showed that high-sugar, high-fat, and high-protein diets promoted the amplification and transfer of exogenous ARGs among intestinal microbiota, and up-regulated the expression of trfAp and trbBp while significantly altered the intestinal microbiota and its metabolites. Inflammation-related products were strongly correlated with the spread of ARGs, suggesting the intestinal microenvironment after diet remodeling might be conducive to the spreading of ARGs. This may be attributed to changes in bacterial membrane permeability, the SOS response, and bacterial composition and diversity caused by diet-induced inflammation. In addition, acceptor bacteria (zygotes) screened by flow cytometry were mostly Proteobacteria, Firmicutes and Actinobacteria, and most were derived from dominant intestinal bacteria remodeled by diet, indicating that the transfer of ARGs was closely linked to diet, and had some selectivity. Metagenomic results showed that the gut resistance genome could be affected not only by diet, but by exogenous antibiotic resistant bacteria (ARB). Many ARG markers coincided with bacterial markers in diet groups. Therefore, dominant bacteria in different diets are important hosts of ARGs in specific dietary environments, but the many pathogenic bacteria present may cause serious harm to human health.

Intramolecular acid-base cooperative catalysis is a powerful strategy to promote the nucleophilic additions in synthetic chemistry, since both substrates and nucleophiles can be activated simultaneously, yielding a lower energy reaction pathway. However, the systems often suffer from catalyst quenching due to the mutual neutralization of acid/base sites. Herein, we doped the boron (B) atoms in the tri-s-triazine ring of graphite-like carbon nitride (g-C3N4) framework, to develop the acid-base cooperative catalyst for nucleophilic addition. Characterization results demonstrated a foam-like hierarchical porous structure, as well as the coexistence of Lewis acid and base sites in the as-synthesized samples. As a result, the B-doped g-C3N4 acted as the efficient acid-base cooperative catalysts, significantly promoting the Knoevenagel condensation whose key step involves in nucleophilic addition. A wide range of α, β-unsaturated carbonyl compounds with remarkably high yields (> 90%) was achieved even within 1 h in water, whereas the acid-free or base-free counterpart was far less efficient. In addition, the bifunctional catalysts exhibited excellent reusability with simple treatment. The novel B-doped g-C3N4 catalytic system offers several advantages, such as operational simplicity, mild reaction conditions, high efficiency, and facile reuse of catalyst. All these advantages make it a benign protocol from the sustainability point of view, and inspired us to design the other bifunctional cooperative catalysts for a wide range of sustainable industrial applications.

Abstract Untethered small robots with multiple functions show considerable potential as next‐generation catheter‐free systems for biomedical applications. However, owing to dynamic blood flow, even effective upstream swimming in blood vessels remains a challenge for the robot, let alone performing medical tasks. This paper presents an untethered millirobot with a streamlined shape that integrates the engine, delivery, and biopsy modules. Based on the proposed spiral‐rolling strategy, this robot can move upstream at a record‐breaking speed of ≈14 mm s−1 against a blood phantom flow of 136 mm s−1. Moreover, benefiting from the bioinspired self‐sealing orifice and easy‐open auto‐closed biopsy needle sheath, this robot facilitates several biomedical tasks in blood vessels, such as in vivo drug delivery, tissue and liquid biopsy, and cell transportation in rabbit arteries. This study will benefit the development of wireless millirobots for controllable, minimally invasive, highly integrated, and multifunctional endovascular interventions and will inspire new designs of miniature devices for biomedical applications.

Abstract Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor ubiquitously associated with the Epstein‐Barr virus (EBV), which is highly prevalent in South China, Southeast Asia, and North Africa. Despite being a highly radio‐sensitive and treatable cancer, a majority of NPC patients are diagnosed in their advanced stage, and locoregional and distant relapses following definitive treatment contribute largely to cancer‐specific mortality among these patients. Given that EBV‐driven NPC is the predominant variant seen in endemic regions, various EBV detection methods have been developed and are utilized in screening, prognostication, and post‐treatment surveillance of NPC patients. While the Immunoglobulin A (IgA) serology assay is the most extensively studied EBV detection method, the detection of plasma EBV DNA released during replication or cellular apoptosis has shown superior outcomes in endemic population screening, prognostication, and detection of distant relapse. Furthermore, there is emerging evidence on the use of circulating tumor cells, microRNAs, DNA hypermethylation, and combination assays in various clinical scenarios. Herein, this paper provides a comprehensive overview of the relevant studies using various EBV detection techniques in the management of NPC. Specifically, the recent advances, clinical evidence, and challenges associated with the clinical application of EBV liquid biopsies in population screening, prognostication, and surveillance of NPC are presented.

Objective: The aims of the current study were to describe the serial CT characteristics of patients infected with COVID-19. In addition, in the light of the CT findings, we tried to determine whether virulence weakens during the transmission with quarantine management.Methods: Demographics, comorbidity, clinical findings, CT scanning, and scores of the affected lung parenchyma were compared for 131 patients with abnormality on CT images classified as COVID-19 pneumonia and the patients were divided between an imported group (n = 83) and indigenous group (n = 48), according to infected location. Two reviewers scored chest CT examinations for segmental involvement, ground glass opacities, consolidation, and honeycombing opacities. The 55 patients with peak CT "severity score" were selected o make a comparative analysis.Results: Patients’ demographics and comorbidities and clinical findings did not differ significantly between the two groups. The CT scores distribution trendline of the third CT scanning was lower than the former CT scanning. The peak CT scores trendline of the 55 selected COVID-19 patients in the indigenous group was lower than the imported group. The ROC analysis revealed an area under curve of 0.714 for the CT scanning with an optimal cutoff scores of 2.55 for prediction of contact history, a sensitivity of 76.3%, and a specificity of 52.9%.The peak CT scores of the imported cases were higher than of the indigenous cases and the lung consolidation predominance on CT findings was remarkable in the imported patients (P < 0.05).Conclusions: CT scanning not only monitored the progression of patients with COVID-19 but also reflected their exposure status to some extent. We suggest that a follow-up CT scanning interval of more than 5 days might be cost effective. The pathogenicity of novel coronavirus may be weakened through transmission under adequate quarantine measures, since indigenous cases have much better progression than imported cases.

Immunosuppressed patients are more likely to suffer from pneumonia, especially Streptococcus and Enterobacter pneumonia. Studies have demonstrated the existence of a complex and dynamic microbiota on the surface of human respiratory epithelial cells, both in healthy and diseased states. However, it is not clear whether the pneumonia in immunosuppressed patients is caused by inhaled oropharyngeal pathogens or abnormal proliferation of pulmonary proteobacteria. In this study, immunosuppressed model was made by intraperitoneal injection of cyclophosphamide and oropharyngeal saliva aspiration was simulated by oral and pharyngeal tracheal instillation of sterilized phosphate buffered saline (PBS). Furthermore, the effects of immunosuppression on the lung microbial community and its metabolism were investigated using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. The 16S rRNA gene sequencing results showed that immunosuppression alone did not change the composition of pulmonary bacteria. Moreover, although the bacteria brought by sterilized PBS from oropharynx to lower respiratory tract changed the composition of the microflora in healthy and immunosuppressed rats, the change in the latter was more obvious. Metabolomic analysis revealed that the levels of pulmonary metabolites were disturbed in the immunosuppressed rats. The altered lung microbiota, including Streptococcaceae and Enterobacteriaceae, showed significant positive correlations with pulmonary metabolites. Our study suggested that the source of the pathogens of pneumonia in immunosuppressed rats was via inhalation and explored the relationship between lung microbiome and metabolites in immunosuppressed rats. Our results provide the basis for the development of prevention and treatment strategies for pneumonia.

Global environmental governance (GEG) is one of the world’s major attempts to address climate change issues through mitigation and adaptation strategies. Despite a significant improvement in GEG’s structural, human, and financial capital, the global commons are decaying at an unprecedented pace. Among the global commons, land has the largest share in GEG. Land use change, which is rooted in increasing populations and urbanization, has a significant role in greenhouse gas (GHG) emissions. As a response, land governance and, consequently, good land governance, have arisen as normative concepts emerging from a series of success factors (notably economic development, environmental conservation, and social justice) to achieve greater sustainability. However, global land governance has shown little success in helping GEG due to the lack of intellectual and flexible thinking over governing the land sector. Consequently, reforming land governance “in a smart way” is one of the most critical actions that could contribute to achieving GEG goals. Hence, we propose a smart land governance (SLG) system that will be well addressed, understood, and modeled in a systemic and dynamic way. A smart system may be smart enough to adapt to different contexts and intellectual responses in a timely fashion. Accordingly, SLG is able to promote shared growth and solve many land sector problems by considering all principles of good land governance. Therefore, in order to enhance adaptive land governance systems, efficient land administration and management are required. This study’s outcomes will raise the comprehension of the problems of land management, providing an excellent framework to help land planners and policy-makers, as well as the development of strategic principles with respect to the principal multidimensional components of SLG.

With the increasing number of drug-resistant bacteria, there is an urgent need for new antimicrobial agents, and antimicrobial peptides (AMPs), which exist in the human non-specific immune system, are one of the most promising candidates. It is an effective optimization strategy to modify antimicrobial peptides (AMPs) according to the distribution of amino acids and hydrophobic characteristics. The addition of bacterial pheromones to the N short peptide can increase the ability to recognize bacteria. In this study, we designed and synthesized AMP1–6 by amino acid substitution of mBjAMP1. Additionally, P-6, S-6, and L-6 were designed and synthesized by adding bacterial pheromones based on 1–6. Functional tests showed that the four AMPs had the ability to kill Gram-negative Vibrio anguillarum, Pseudomonas mendocina, and Vibrio parahaemolyticus, and Gram-positive Micrococcus luteus and Listeria monocytogenes. Additionally, all four AMPs induced permeabilization and depolarization of bacterial cell membranes and increased intracellular reactive oxygen species (ROS) levels. Importantly, they had little or no mammalian cytotoxicity. At the same time, 1–6 and L-6 protected the stability of intestinal flora in Sebastes schlegelii and increased the relative abundance of Lactobacillaceae. In summary, our results indicate that the designed AMPs have broad application prospects as a new type of polypeptide antimicrobial agent.

With the rapid development of edge computing technology, the scale of the network continues to expand. Various types of applications are becoming more widespread. In the edge computing, existing network agents, NAT, IP tunneling technologies, and rapidly evolving anonymous communication systems provide convenience for attackers to hide real IP. In addition, the attacker forms a “stepping” chain by breaking through several intermediate systems of the edge computing network. Thereby implementing an invisible intrusion attack across multiple autonomous domains can increase the difficulty of intrusion tracking. Aiming at the problem of insufficient applicability of existing interval centroid based watermarking technique, this paper proposes a histogram specified interval centroid-based watermarking technique. It improves cross-domain collaborative intrusion tracking. This technique improves the resistance of the prior art to multi-flow attacks in edge computing. It decreases the time and space overhead of the detector. Compared with other interval centroid based watermarking techniques, this method has stronger concealment. The proposed method can effectively defend against multi-flow attacks of edge computing. The time and space overhead of the detector can be reduced when multiple attack flows are tracked in parallel. Thus, it is suitable for edge computing. The robustness and adaptability are improved by this method.

An unhealthy diet has been linked to increased incidence of chronic diseases. To investigate the relationship between diet and intestinal inflammation, mice in two experimental groups were fed on a high-fat diet or high-fructose diet, respectively. The result showed that the defecation volume of the experimental groups was significantly reduced compared with that of the control group, and the levels of pro-inflammatory cytokines (interleukin (IL)-1β and IL-6) and IgG in serum were increased significantly. In addition, inflammatory cell infiltration was observed in intestinal tissue, indicating that a high-fructose or high-fat diet can lead to constipation and inflammation. Further analysis showed that the microbial composition of the experimental groups changed significantly, including a decrease of the Bacteroidetes/Firmicutes ratio and increased levels of Bacteroides, Akkermansia, Lactobacillus, and Ruminococcus, which might be associated with inflammation. The results of pro-inflammatory metabolites analysis showed that the levels of arachidonic acid, stearic acid, and indoxylsulfuric acid were significantly increased in the experimental groups, which were related significantly to Bacteroides, Enterococcus, and Akkermansia. Meanwhile, the content of 5-hydroxytryptamine (5-HT) was significantly decreased, which might cause constipation by reducing intestinal peristalsis. Moreover, transplantation of fecal bacteria from inflammatory mice caused constipation and inflammation in normal mice, which could be relieved by feeding a normal diet. The results of the present study indicated that changes in intestinal microbiota and microbial metabolites may underlie chronic intestinal inflammation and constipation caused by high-fructose and high-fat diets.

Developing small‐scale soft continuum robots with large‐angle steering capacity and high‐precision manipulation offers broad opportunities in various biomedical settings. However, existing continuum robots reach the bottleneck in actuation on account of the contradiction among small size, compliance actuation, large tender range, high precision, and small dynamic error. Herein, a 3D‐printed millimeter‐scale soft continuum robot with an ultrathin hollow skeleton wall (300 μm) and a large inner‐to‐outer ratio (0.8) is reported. After coating a thin ferromagnetic elastomer layer (≈100–150 μm), the proposed soft continuum robot equipped with hybrid actuation (tendon‐ and magnetic‐driven mode) achieves large‐angle (up to 100°) steering and high‐precision (low to 2 μm for static positioning) micromanipulation simultaneously. Specifically, the robot implements an ultralow dynamic tracking error of ≈10 μm, which is ≈30‐fold improved than the state of art. Combined with a microneedle/knife or nasopharyngeal swab, the robot reveals the potential for versatile biomedical applications, such as drug injection on the target tissue, diseased tissue ablation, and COVID‐19 nasopharyngeal sampling. The proposed millimeter‐scale soft continuum robot presents remarkable advances in large‐range and high‐precise actuation, which provides a new method for miniature continuum robot design and finds broad applications in biomedical engineering.

Summary: Tumor acquired radioresistance remains as the major limit in cancer radiotherapy (RT). Rab25, a receptor recycling protein, has been reported to be enhanced in tumors with aggressive phenotype and chemotherapy resistance. In this study, elevated Rab25 expression was identified in an array of radioresistant human cancer cell lines, in vivo radioresistant xenograft tumors. Clinical investigation confirmed that Rab25 expression was also associated with a worse prognosis in patients with lung adenocarcinoma (LUAD) and nasopharyngeal carcinoma (NPC). Enhanced activities of EGFR were observed in both NPC and LUAD radioresistant cells. Rab25 interacts with EGFR to enhance EGFR recycling to cell surface and to decrease degradation in cytoplasm. Inhibition of Rab25 showed synergized radiosensitivity with reduced aggressive phenotype. This study provides the clinical and experimental evidence that Rab25 is a potential therapeutic target to alleviate the hyperactive EGFR signaling and to prevent RT-acquired tumor resistance in patients with LUAD and NPC. : Radiation Biology; Molecular Biology; Cell Biology; Cancer Subject Areas: Radiation Biology, Molecular Biology, Cell Biology, Cancer

Few studies have attempted to investigate the impact of airports on the ecological environment. This paper compares the effects of airports in China and Germany on the surrounding ecological environment and discusses the underlying institutional mechanisms that lead to these impacts. We used remote-sensing ecological indicators to assess ecological environment quality. A buffer analysis was used to determine the influence scopes of airports on the ecological environment. The institutional analysis development framework was adopted to investigate the functions of different institutions on the influence scopes and intensities. The results showed that the Chinese airport had obvious negative effects and that its impact scope was wide, while the impact intensity of the German airport was weaker. These significant differences stem from the distinct institutional systems that structure the two airports. Our findings ultimately provide insight into how to improve the relationship between infrastructure construction and environmental protection in China.

Summary: Radiation resistance is a critical problem in radiotherapy for cancer. Radiation kills tumor cells mainly through causing DNA damage. Thus, efficiency of DNA damage repair is one of the most important factors that limits radiotherapy efficacy. Glutamine physiologically functions to generate protein and nucleotides. Here, we study the impact of glutamine metabolism on cancer therapeutic responses, in particular under irradiation-induced stress. We show that radiation-resistant cells possessed low glycolysis, mitochondrial respiration, and TCA cycle but high glutamine anabolism. Transcriptome analyses revealed that glutamine synthetase (GS), an enzyme catalyzing glutamate and ammonia to glutamine, was responsible for the metabolic alteration. ChIP and luciferase reporter assays revealed that GS could be transcriptionally regulated by STAT5. Knockdown of GS delayed DNA repair, weakened nucleotide metabolism, and enhanced radiosensitivity both in vitro and in vivo. Our data show that GS links glutamine metabolism to radiotherapy response through fueling nucleotide synthesis and accelerating DNA repair. : Radiation resistance is one of the limiting factors for therapeutic efficacy and results in cancer recurrence. Fu et al. identify GS as a switch that drives cellular metabolic flux toward nucleotide synthesis for efficient DNA repair and thus leads to radiation resistance of cancer cells. Keywords: glutamine synthetase, radiation resistance, DNA damage repair

With the aim of improving farmland use efficiency without damaging the social function of farmland, Chinese policymakers have proposed the ‘trifurcation of land rights’ reform. When it comes to realization of the law, however, neither the Ownership Model nor the Bundle of Sticks Model can adequately explain this reform. The tree concept of property, which provides a new perspective in delineating property rights based on the function served by specific properties, is thus adopted. We find that this tree concept of property helps to better understand and realize the trifurcated rights on farmland in China. Also, a balance between the social and economic functions of farmland can be reached through reconstruction of the property rights involved, a process which comprises three steps: identification of the nature of the newly-established rights; configuration of the rights and duties of relevant entities; and state intervention in the enforcement of relevant rights with the aim of realizing certain social values. Finally, this paper argues that success of this trifurcated structure requires a systematic design of the Chinese Civil Code. In particular, it requests further improvements in legal rules on farmland lease.

The cooperative movement in Poland has a long but difficult history, which has caused farmers to have an aversion to cooperatives. Nonetheless, in the early 1990s, the first farmers' cooperative marketing organizations, which were called agricultural producer groups, appeared in the market. These groups are bottom-up, voluntary organizations the primary purpose of which is to jointly sell their members' output. In this paper, it is investigated why the new forms of governance, namely cooperative arrangements, were chosen, and we evaluate the implications of these choices on the market success of these groups. Empirical data were collected from 62 producer groups in one Polish province. We found that the groups were typically functioning as associations, unions, and limited liability companies. The factors that had an impact on the choices made were the number of members and the specific investment per member. Additionally, if the initial investment level was low, not only set-up and operational costs but also tax considerations played a role in the decision. Therefore, we argue that the new bottom-up cooperatives, which are theoretically suitable when the start-up capital is high or the number of members is large, will gradually be recognized and accepted in the market despite the fact that these cooperatives have a "bad reputation" caused by the socialist legacy. The new cooperative development trend confirms this argument.

Acute aortic dissection (AAD) is a life-threatening disease. Despite the higher risk of mortality, currently there are no effective therapies that can ameliorate AAD development or progression. Identification of meaningful clusters of co-expressed genes or representative biomarkers for AAD may help to identify new pathomechanisms and foster development of new therapies. To this end, we performed a weighted gene co-expression network analysis (WGCNA) and calculated module-trait correlations based on a public microarray dataset (GSE 52093) and discovered 9 modules were found to be related to AAD. The module which has the strongest positive correlation with AAD was further analyzed and the top 10 hub genes SLC20A1, GINS2, CNN1, FAM198B, MAD2L2, UBE2T, FKBP11, SLMAP, CCDC34, and GALK1 were identified. Furthermore, we validated the data by qRT-PCR in an independent sample set originated from our study center. Overall, the qRT-PCR results were consistent with the results of the microarray analysis. Intriguingly, the highest change was found for FKBP11, a protein belongs to the FKBP family of peptidyl-prolyl cis/trans isomerases, which catalyze the folding of proline-containing polypeptides. In congruent with the gene expression analysis, FKBP11 expression was induced in cultured endothelial cells by angiotensin II treatment and endothelium of the dissected aorta. More importantly we show that FKBP11 provokes inflammation in endothelial cells by interacting with NF-kB p65 subunit, resulting in pro-inflammatory cytokines production. Accordingly, siRNA mediated knockdown of FKBP11 in cultured endothelial cells suppressed angiotensin II induced monocyte transmigration through the endothelial monolayer. Based on these data, we hypothesize that pro-inflammatory cytokines elicited by FKBP11 overexpression in the endothelium under AAD condition could facilitate transendothelial migration of the circulating monocytes into the aorta, where they differentiate into active macrophages and secrete MMPs and other extracellular matrix (ECM) degrading proteins, contributing to sustained inflammation and AAD. Taken together, our data identify important role of FKBP11 which can serve as biomarker and/or therapeutic target for AAD.

In sustainability research, archetype analysis reveals patterns of factors and processes that repeatedly shape social-ecological systems. These patterns help improve our understanding of global concerns, including vulnerability, land management, food security, and governance. During the last decade, the portfolio of methods used to investigate archetypes has been growing rapidly. However, these methods differ widely in their epistemological and normative underpinnings, data requirements, and suitability to address particular research purposes. Therefore, guidance is needed for systematically choosing methods in archetype analysis. We synthesize strengths and weaknesses of key methods used to identify archetypes. Demonstrating that there is no "one-size-fits-all" approach, we discuss advantages and shortcomings of a range of methods for archetype analysis in sustainability research along gradients that capture the treatment of causality, normativity, spatial variations, and temporal dynamics. Based on this discussion, we highlight seven analytical frontiers that bear particular potential for tackling methodological limitations. As a milestone in archetype analysis, our synthesis supports researchers in reflecting on methodological implications, including opportunities and limitations related to causality, normativity, space, and time considerations in view of specific purposes and research questions. This enables innovative research designs in future archetype analysis, thereby contributing to the advancement of sustainability research and decision-making.

Against the backdrop of rural deprivation during the rapid urbanization of China since the end of the previous century, rural renewal has been regarded as a vital strategy for facilitating rural sustainability. Rural renewal in contemporary China involves activities that replan, consolidate, and redevelop the extant and idle rural construction land and then convert such land for alternative uses, including new rural settlement construction and rural industry development. However, given the regionally decentralized authoritarian (RDA) regime of China, i.e., a combination of political centralization and economic regional decentralization, the governance of rural renewal and its performance show great diversity. The objective of this study was to explore and elucidate the underlying patterns of sustainable rural renewal. Thus, from the social-ecological systems (SES) perspective, an archetype analysis was conducted based on primary data from 27 cases from the eastern, central, and western parts of China. In total, eight archetypical patterns were extracted, and the following three overarching implications were observed: (1) a governance system aligning with the attributes of rural land resources, the characteristics of actors, and the properties of interactions is essential for sustainable rural renewal; (2) decentralized or self-organized governance emerges to facilitate sustainable rural renewal; and (3) a long-term perspective of designing and enforcing rural renewal and distinctive land resource endowment contribute to rural sustainability. These findings may benefit China and other regions pursuing rural sustainability.

BackgroundIt is well-recognized that diabetes represents a powerful independent risk factor for cardiovascular diseases. However, very few studies have investigated the relationship between diabetes and risk of aortic dissection (AD).AimThe aim of this case-control study was to evaluate the association between diabetes and risk of AD in Chinese population.MethodsA hospital-based case-control study, consisting of 2160 AD patients and 4320 controls, was conducted in a Chinese population. Demographic, clinical characteristics and risk factors were collected. Diabetes rate of patients with overall AD, Stanford type A AD and type B AD group was compared with that of corresponding matched control groups. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) for relationship between diabetes and AD risk.ResultsThe prevalence of diabetes was lower in AD cases than that of control subjects, whether it is the overall AD, type A AD or type B AD group (4.7% vs. 10.0%, 2.9% vs. 8.8%, 5.9% vs. 10.9%, all PConclusionsWe observed the paradoxical inverse relationship between DM and risk of AD in the Chinese population. These results suggest diabetes may play a protective role in the development of AD. However, further studies are needed to enrich related evidence, especially with regard to underlying mechanisms for these trends.