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Background Osteosarcoma is the most common primary bone tumor in children and adolescents. Unfortunately, osteosarcoma treatments often fail due to the development of chemoresistance, of which the underlying molecular mechanisms still remain unclear. In this study, we demonstrated that HSP90AA1 gene is responsible for drug resistance in osteosarcoma through an autophagy-related mechanism. Methods shRNAs were transfected into osteosarcoma cells for knockdown of HSP90AA1 gene. Stable HSP90AA1 overexpressing osteosarcoma cell lines were obtained by lentivirus infection. mRNA and protein expressions of HSP90AA1 in osteosarcoma cells were tested by quantitative real-time PCR and western blot, respectively. Autophagy of osteosarcoma cells was detected by western blot of LC3, transmission electron microscopy and fluorescence microscope. mRFP-GFP-LC3 lentiviral transfection was also performed to detect autophagic flux. NOD/SCID mices were inoculated with MG-63 tumor cells transfected with HSP90AA1 specific shRNA. TUNEL and LC3 staining were performed to detect apoptosis and autophagy of resected tumor tissues. Results Doxorubicin, cisplatin, and methotrexate, which are commonly used in chemotherapy, each induced HSP90AA1 upregulation in human osteosarcoma cells. Suppression of HSP90AA1 restored the sensitivity of osteosarcoma cells to chemotherapy both in vivo and in vitro. Mechanism study indicated that autophagy is responsible for the chemoresistance in osteosarcoma cells. HSP90AA1 increased drug resistance by inducing autophagy and inhibiting apoptosis. Suppression of HSP90AA1 diminished autophagic protection in response to chemotherapy in osteosarcoma cells. Moreover, HSP90AA1 promotes autophagy through PI3K/Akt/mTOR pathway and inhibits apoptosis through JNK/P38 pathway. Conclusion We showed that chemotherapy agents can induce HSP90AA1 expression in osteosarcoma cells. And HSP90AA1, acting as an important regulator of autophagy, is a critical factor in the development of osteosarcoma chemoresistance both in vitro and in vivo. HSP90AA1 provides a novel therapeutic target for improving osteosarcoma treatment.

The perovskite solar cell has emerged rapidly in the field of photovoltaics as it combines the merits of low cost, high efficiency, and excellent mechanical flexibility for versatile applications. However, there are significant concerns regarding its operational stability and mechanical robustness. Most of the previously reported approaches to address these concerns entail separate engineering of perovskite and charge-transporting layers. Herein we present a holistic design of perovskite and charge-transporting layers by synthesizing an interpenetrating perovskite/electron-transporting-layer interface. This interface is reaction-formed between a tin dioxide layer containing excess organic halide and a perovskite layer containing excess lead halide. Perovskite solar cells with such interfaces deliver efficiencies up to 22.2% and 20.1% for rigid and flexible versions, respectively. Long-term (1000 h) operational stability is demonstrated and the flexible devices show high endurance against mechanical-bending (2500 cycles) fatigue. Mechanistic insights into the relationship between the interpenetrating interface structure and performance enhancement are provided based on comprehensive, advanced, microscopic characterizations. This study highlights interface integrity as an important factor for designing efficient, operationally-stable, and mechanically-robust solar cells. Operational stability and mechanical robustness remain as engineering bottlenecks in perovskite solar cells technology. Here, Dong et al. introduce an interpenetrating perovskite at the electron-transporting-layer interface that enables a 1000-hour stable operation and high endurance against bending fatigue over 2500 cycles.

This paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health. A self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China. The overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p < 0.05), while their average interpersonal sensitivity score was significantly lower (p < 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified (all p < 0.05). The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China.

In view of the issues including the incomplete identification of alternatives and difficulty in tracing pollution sources in PFAS pollution monitoring in surface water, this study took typical surface waters with intensive human activities as the object to perform PFAS screening. A nontarget analysis based on high-resolution mass spectrometry was developed, coupled with a modified solid phase extraction pretreatment method, to achieve the comprehensive screening of 12 legacy carboxylic acids and sulfonic acids, as well as 2 novel alternatives in water. Surface water samples were collected from typical functional areas of human activity to reveal the spatial differential distribution of PFAS concentrations. The long-chain PFASs showed a high detected concentration, among which PFOS, PFUnDA, and PFOA concentrations were especially high in urban complex pollution areas, while PFDA, PFOS, and PFOA were the main components in agricultural areas. The two exposure patterns showed a certain degree of differentiation, which may be related to different pollution sources. PFASs with a long carbon chain, especially chlorine-substituted sulfonic acid, are high-persistent-risk substances. This study provided the data basis for the prevention and control of PFAS pollution in surface water, and supported the treatment of emerging pollutants in the region.

Background Chronic Kidney Disease (CKD) is a growing global health issue with a complex symptom phenotype. It negatively impacts patients’ health-related quality of life and increases healthcare utilization. While digital health interventions offer promising avenues for improving symptom management in CKD, understanding their development, validation, and effectiveness is crucial for clinical application. Objective To comprehensively map the existing literature on digital health interventions designed to manage symptoms in patients with Chronic Kidney Disease (CKD), using the UK Medical Research Council’s complex intervention framework as a guiding lens. This scoping review aims to: (1) catalogue digital health interventions utilized in CKD symptom management; (2) detail the range of outcome measures assessing intervention effectiveness, including clinical efficacy, patient adherence, and quality of life; (3) examine the methodologies and frameworks employed in the creation of these interventions; (4) assess the pilot testing and effectiveness evaluations; and (5) categorize and analyze the barriers to implementation. Methods A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Databases searched included PubMed, Scopus, Embase, and others, covering literature up to December 2023. Studies were selected based on predefined eligibility criteria for digital health interventions for CKD symptom management. Results The search yielded 31 studies, with a mix of development and validation studies, predominantly from developed countries. The review highlights the potential of digital interventions in enhancing symptom management, quality of life, and patient engagement in CKD care. However, gaps were identified as follows: (1) Iterative refinement cycles involving multidisciplinary stakeholders enhanced intervention acceptability and usability should be guaranteed, (2) Theory-driven and evidence-based approaches were underutilized in current intervention development, (3) Long-term implementation outcomes and process evaluations were rarely assessed. This review maps an evolving landscape where digital health interventions offer patient-centric solutions for CKD symptom management while highlighting opportunities for methodological advancements. Conclusion Digital health interventions hold promise for improving symptom management in CKD, yet more research is needed to overcome current limitations and fully realize their potential. Future studies should focus on patient-centred designs, comprehensive validation processes, exploring the underlying mechanism using process evaluation and the integration of these technologies into routine clinical practice.

Equipment failures and communication interruptions of satellites, aircraft and ground devices lead to data loss in Space-Air-Ground Integrated Internet of Things (SAGIoT). The incomplete data affect the accuracy of data modeling, decision-making and spectrum prediction. Reconstructing the incomplete data of electromagnetic environment is a significant task in the SAGIoT. Most spectral data completion algorithms have the problem of limited accuracy and slow iterative optimization. In light of these challenges, a novel high-precision reconstruction method for electromagnetic environment data based on multi-component time series generation adversarial network (MTS-GAN) is proposed in this paper. MTS-GAN transforms the reconstruction method of electromagnetic environment data into the data generation problem of multiple time series. It extracts the time–frequency joint features and the overall distribution of electromagnetic environment data. To improve the reconstruction precision, MTS-GAN simulates the time irregularity of incomplete time series by applying a gate recursive element to adapt to the attenuation effect of discontinuous time series observations. Experimental results show that the proposed MTS-GAN provides high completion accuracy and achieves better results than competitive data completion algorithms.

The evolution of macromolecular complex is a fundamental biological question, which is related to the origin of life and also guides our practice in synthetic biology. The chemosensory system is one of the complex structures that evolved very early in bacteria and displays enormous diversity and complexity in terms of composition and array structure in modern species. However, how the diversity and complexity of the chemosensory system evolved remains unclear. Here, using the Campylobacterota phylum with a robust “eco-evo” framework, we investigated the co-evolution of the chemosensory system and one of its important signaling outputs, flagellar machinery. Our analyses show that substantial flagellar gene alterations will lead to switch of its primary chemosensory class from one to another, or result in a hybrid of two classes. Unexpectedly, we discovered that the high-torque generating flagellar motor structure of Campylobacter jejuni and Helicobacter pylori likely evolved in the last common ancestor of the Campylobacterota phylum. Later lineages that experienced significant flagellar alterations lost some key components of complex scaffolding structures, thus derived simpler structures than their ancestor. Overall, this study revealed the co-evolutionary path of the chemosensory system and flagellar system, and highlights that the evolution of flagellar structural complexity requires more investigation in the Bacteria domain based on a resolved phylogenetic framework, with no assumptions on the evolutionary direction.

Background To investigate the clinical characteristics, treatment response, and prognosis of patients with methylmalonic acidemia (MMA) and homocysteinemia complicated by cardiovascular manifestations and to raise awareness regarding MMA and homocysteinemia. Methods A total of 16 children diagnosed with MMA and homocysteinemia with cardiovascular manifestations who were admitted to the Department of Pediatrics of the Second Hospital of Hebei Medical University from June 2018 to October 2024 were retrospectively analyzed. Results All 16 patients had varying degrees of neurological manifestations, and all had cardiovascular manifestations, 3 patients were diagnosed with MMA and homocysteinemia by newborn screening and received conventional treatment, the remaining 13 patients had nausea, vomiting, anemia, recurrent pneumonitis, respiratory distress, and lethargy as their first symptoms. Cardiovascular complications were found between the ages of 2 months and 12 years, with 9 patients having pulmonary hypertension, 7 having hypertension, and 5 having non-compaction of ventricular myocardium. Fourteen of these cases were confirmed to have CblC-type methylmalonic acidemia caused by mutations in the MMACHC gene by genetic testing. The most common mutations were c.80A > G (p.Q27R) (8 cases) and c.609G > A (p.W203X) (8 cases). Conclusion Cardiovascular manifestation is uncommon in patients with MMA and homocysteinemia, but it is usually critical cause of death. When unexplained pulmonary hypertension or hypertension occurs, MMA and homocysteinemia should be suspected, especially when accompanied by manifestations of other systems.

Species of the phylum Actinobacteria have long time been thought mostly non-motile and non-flagellated, in spite of their extraordinary diversity in morphology, physiology, and ecology. It remains unclear how very few actinobacterial species acquired their flagellar genes and the role of flagellar motility in the evolution of different lineages within this large phylum. Here, we performed a comprehensive phylogenomic analysis of flagellar components in all actinobacterial species, including the deepest branches of this phylum identified recently. Our results provide robust evidence that all actinobacterial flagella shared a common origin and likely evolved from their last common flagellated ancestor by vertical inheritance. Later lineages underwent massive flagellar losses with the ecological switch from aquatic to terrestrial land or host-associated environments. In addition, the actinobacterial flagella also showed degenerative evolution in terms of their composition, leading to the simplest rod known so far. Furthermore, these evolutionary changes of flagella were accompanied by noteworthy variations in the chemosensory system and c-di-GMP mediated signaling network. Overall, we present here a detailed picture of flagellar evolution in Actinobacteria , which provides new insights into the evolution of major actinobacterial lineages and previously unobserved links between flagella and other biological features. The simplest flagellar rod as a product of degenerative evolution could possibly serve as a model for future nanomachine reconstruction in synthetic biology. Flagellar motility plays an important role in the environmental adaptation of bacteria and is found in more than 50% of known bacterial species. However, this important characteristic is sparsely distributed within members of the phylum Actinobacteria , which constitutes one of the largest bacterial groups. It is unclear why this important fitness organelle is absent in most actinobacterial species and the origin of flagellar genes in other species. Here, we present detailed analyses of the evolution of flagellar genes in Actinobacteria , in conjunction with the ecological distribution and cell biological features of major actinobacterial lineages, and the co-evolution of signal transduction systems. The results presented in addition to clarifying the puzzle of sporadic distribution of flagellar motility in Actinobacteria , also provide important insights into the evolution of major lineages within this phylum.