Low-energy shock waves promote the cisplatin chemosensitivity of human osteosarcoma MNNG/HOS cells via the P2X7/Akt/mTOR pathway.

Background: The current dilemma of osteosarcoma treatment is the resistance of chemotherapeutic drugs after long-term usage, which also introduces life-threatening side effects. Methods and results: To minimize chemoresistance in osteosarcoma patients, the authors applied shock waves (SWs) to human osteosarcoma MNNG/HOS cells, then evaluated the cell viability and extracellular ATP levels, and further investigated the effect of SWs on cisplatin (DDP) cytotoxicity in MNNG/HOS cells. The authors' results showed that 400 SW pulses at 0.21 mJ/mm2 exhibited little influence on the MNNG/HOS cell viability. In addition, this SW condition significantly promoted the extracellular ATP release in MNNG/HOS cells. Importantly, low-energy SWs obviously increased Akt and mammalian target of rapamycin (mTOR) phosphorylation and activation in MNNG/HOS cells, which could be partially reversed in the presence of P2X7 siRNA. The authors also found that low-energy SWs strongly increased the DDP sensitivity of MNNG/HOS cells in the absence of P2X7. Conclusions: For the first time, the authors found that SW therapy reduced the DDP resistance of MNNG/HOS osteosarcoma cells when the ATP receptor P2X7 was downregulated. SW therapy may provide a novel treatment strategy for chemoresistant human osteosarcoma.

Electrochemiluminescence-Based Single-Particle Tracking of the Biomolecules Moving along Intercellular Membrane Nanotubes between Live Cells.

Electrochemiluminescence (ECL) imaging, a rapidly evolving technology, has attracted significant attention in the field of cellular imaging. However, its primary limitation lies in its inability to analyze the motion behaviors of individual particles in live cellular environments. In this study, we leveraged the exceptional ECL properties of quantum dots (QDs) and the excellent electrochemical properties of carbon dots (CDs) to develop a high-brightness ECL nanoprobe (CDs-QDs) for real-time ECL imaging between living cells. This nanoprobe has excellent signal-to-noise ratio imaging capabilities for the single-particle tracking (SPT) of biomolecules. Our finding elucidated the enhanced ECL mechanism of CDs-QDs in the presence of reactive oxygen species through photoluminescence, electrochemistry, and ECL techniques. We further tracked the movement of single particles on membrane nanotubes between live cells and confirmed that the ECL-based SPT technique using CD-QD nanoparticles is an effective approach for monitoring the transport behaviors of biomolecules on membrane nanotubes between live cells. This opens a promising avenue for the advancement of ECL-based single-particle detection and the dynamic quantitative imaging of biomolecules.

Didymium arenosum, a myxomycete new to science from the confluence of deserts in northwestern China.

A new myxomycete species, Didymium arenosum, was described based on morphological evidence and phylogenetic analyses. The species was discovered in the arid region at the confluence of the Badain Jaran desert and Tengger desert on the leaves of Betula platyphylla and was cultivated in a moist chamber culture. Morphologically, the species is distinguished by the greenish-yellow calcium carbonate crystals on the surface and the spores covered with small warts, some of which are connected into a short line. A phylogenetic analysis of D. arenosum strongly supports its classification as a separate clade. The spore to spore agar culture of D. arenosum requires 23 days, and this study provides a detailed description of its life cycle.

Distribution characteristics and diversity of myxomycetes in three parallel rivers in Yunnan, China.

Three Parallel Rivers is one of the world's biodiversity hotspots. However, the research on myxomycetes diversity is scarce in this area. Random sampling was used to investigate myxomycetes' diversity and distribution characteristics in this area. One hundred and seventeen species, including three varieties, were obtained, belonging to 28 genera, nine families, and six orders, with Arcyria cinerea and Physarum viride being the dominant species. Moreover, four species and one variety were first reported in China. Twenty-six species and one variety were first reported in Yunnan Province. The species' most commonly utilized substrate for fruiting bodies was decaying wood, and Cribraria was the dominant genus. The species diversity was most abundant in mixed broadleaf-conifer forests. Species similarity between coniferous and broad-leaved forests was much higher than the pairwise comparison of other forest types. NMDS analysis shows that substrate and forest types had insignificant effects on myxomycetes communities, while river valley had a significant effect. The myxomycetes community similarity between river valleys is unrelated to geographical proximity.

[Advantages, development opportunities, and practice paths of traditional Chinese medicine in prevention and treatment of elderly comorbidities].

This article focused on the significant public health issue of comorbidities in the elderly population and highlighted the important role of traditional Chinese medicine(TCM) in the prevention and treatment of comorbidities in the elderly. It suggested that TCM should fully utilize its advantages in holistic perspective, syndrome differentiation and treatment, and preventive medicine in the process of preventing and treating comorbidities in the elderly. At the same time, in response to the significant shift in the disease spectrum of the elderly, the increasingly innovative concepts in diagnosis and treatment, the growing demand for proactive health by the el-derly population, and the current emphasis on patient-centered evaluation standards, it is necessary to further conduct basic theoretical and experimental research on comorbidities in the elderly using TCM, emphasize clinical research on comorbidities in the elderly, explore appropriate efficacy evaluation systems, improve TCM prevention and treatment strategies and comprehensive intervention programs for comorbidities in the elderly, and leverage the unique role of TCM in the rehabilitation of elderly comorbidity patients. By analyzing the potential of TCM in the field of comorbidities in the elderly, this article is expected to provide new insights for future clinical practice and scientific research.

Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes.

BACKGROUND: Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear. AIM: To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes. METHODS: This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments. RESULTS: According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats. CONCLUSION: This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.

Genome size and GC content of myxomycetes.

More than 1272 myxomycetes species have been described, accounting for more than half of all Amoebozoa species. However, the genome size of only three myxomycetes species has been reported. Therefore, we used flow cytometry to present an extensive survey and a phylogeny-based analysis of genome size and GC content evolution in 144 myxomycetes species. The genome size of myxomycetes ranged from 18.7 Mb to 470.3 Mb, and the GC content ranged from 38.7% to 70.1%. Bright-spored clade showed larger genome sizes and more intra-order genome size variations than the dark-spored clade. GC content and genome size were positively correlated in both bright-spored and dark-spored clades, and spore size was positively correlated with genome size and GC content in the bright-spored clade. We provided the first genome size data set in Myxomycetes, and our results will provide helpful information for future Myxomycetes studies, such as genome sequencing.

Effectiveness of price limits: Evidence from China's ChiNext market.

Starting from August 24, 2020, the daily stock price limits in China's ChiNext market have been adjusted from 10% to 20%. We use this reform to study the effectiveness of price limits in China's stock market. We test four hypotheses about price limits: delayed price discovery, volatility spillover, trading interference, and magnet effect. Using the event study method, we examine the differences in the behavior of stock price, trading volume, and volatility before and after the reform. We confirm the delayed price discovery, volatility spillover and trading interference hypothesis of price limits, and find that these negative effects of price limits are more serious when lower limits are hit. In addition, we examine the distribution of large price movements before and after the reform and find no evidence of the magnet effect of price limits. The present research has important implications for policymakers and investors in China's stock market.

Assessment of Fungal Diversity in Minqin County, a Typical Arid Region in Northwestern China.

Minqin County is located in the Shiyang River Basin. As a typical arid area, it is eroded by the Badain Jaran and Tengger Desert all year round, and knowledge of the fungal diversity in this area is limited. Therefore, fungal community structure and distribution in the soil of the artificial forest, desert transition zone, farmland, and desert were investigated using amplicon sequencing of the fungal ITS gene. Ten fungal phyla and 23 classes were identified, including 1131 fungi OTUs, Sordariomycetes, Dothideomycetes, Pezizomycetes, and Agaricomycetes were the most abundant classes. Although most OTUs are shared among habitats, fungal community composition among samples was highly variable, which may influence the design of restoration practices in this area.

Stem cell-derived exosomes for chronic wound repair.

Stem cells possess the capability of self-renewal and multipotency, which endows them with great application potential in wound repair fields. Yet, several problems including immune concerns, ethical debates, and oncogenicity impede the broad and deep advance of stem cell-based products. Recently, owing to their abundant resources, excellent biocompatibility, and ease of being engineered, stem cell-derived exosomes were proved to be promising nanomedicine for curing chronic wounds. What is more, stem cell-derived exosomes are almost the mini record of their maternal cells, which even equipped them with the unique characteristics of stem cells. Chronic wound healing efficacy is dominated by several complicated factors, especially the excessive inflammation conditions and impaired vessels. Therefore, this review tries to concentrate on the current advances of stem cell-derived exosomes for reducing inflammation and promoting angiogenesis in chronic wound healing processes. Last but not least, the existing limitations and future perspectives of stem cell-derived exosomes for chronic wound treatment are also outlined.

Treatment of pediatric tibial shaft nonunion using ipsilateral free non-vascularized fibular graft.

BACKGROUND: Although tibial shaft fractures are the third most common long bone fractures in children after the forearm and femur, nonunion of these fractures are rare in the pediatric population. CASE REPORT: Despite seldom seen, tibial nonunion is very complex and it is also a devastating complication of tibial fracture especially when infected. Numerous methods have been employed to treat pediatric tibial nonunion, but there is no consensus. Here, we present a case of a child with right tibial shaft fracture nonunion. We treated this patient with ipsilateral free non-vascularized fibular graft. RESULTS: Both the nonunion site and fibular donor site united well with good function in the injured extremity and no adverse events. CONCLUSION: We recommend the use of ipsilateral free non-vascularized fibular graft for the treatment of pediatric tibial shaft nonunion.

Competition between H4PteGlu and H2PtePAS Confers para-Aminosalicylic Acid Resistance in Mycobacterium tuberculosis.

Tuberculosis remains a serious challenge to human health worldwide. para-Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by Mycobacterium tuberculosis (M. tuberculosis) dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene thyA caused PAS resistance in M. tuberculosis, but the mechanism is unclear. Here we showed that deleting thyA in M. tuberculosis resulted in increased content of tetrahydrofolate (H4PteGlu) in bacterial cells as they rely on the other thymidylate synthase ThyX to synthesize thymidylate, which produces H4PteGlu during the process. Subsequently, data of in vitro enzymatic activity experiments showed that H4PteGlu hinders PAS activation by competing with hydroxy dihydropteroate (H2PtePAS) for FolC catalysis. Meanwhile, over-expressing folC in ΔthyA strain and a PAS resistant clinical isolate with known thyA mutation partially restored PAS sensitivity, which relieved the competition between H4PteGlu and H2PtePAS. Thus, loss of function mutations in thyA led to increased H4PteGlu content in bacterial cells, which competed with H2PtePAS for catalysis by FolC and hence hindered the activation of PAS, leading to decreased production of hydroxyl dihydrofolate (H2PtePAS-Glu) and finally caused PAS resistance. On the other hand, functional deficiency of thyA in M. tuberculosis pushes the bacterium switch to an unidentified dihydrofolate reductase for H4PteGlu biosynthesis, which might also contribute to the PAS resistance phenotype. Our study revealed how thyA mutations confer PAS resistance in M. tuberculosis and provided new insights into studies on the folate metabolism of the bacterium.

Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice / 药学学报

GJ-4 is crocin enrichments extracted from Gardenia jasminoides J. Ellis, and our previous studies have shown that GJ-4 significantly improved learning and memory impairment induced by Aβ in mice. Herein, a memory deficit model was developed by injecting okadaic acid (OA) into the lateral ventricle of mice, and the neuroprotection and underlying mechanism of GJ-4 on neuronal injury caused by Tau hyperphosphorylation were investigated. The Animal Care & Welfare Committee, Institute of Materia Medica, CAMS & PUMC has approved all procedures (No.00000318). GJ-4 at different doses was intragastric administration to mice for 16 days. Step-down test and Morris water maze test showed that GJ-4 could significantly improve OA-induced memory impairment in mice, and reduced the loss of Nissl bodies in the hippocampus of mice. GJ-4 could also decrease the phosphorylation level of Tau protein at Ser396, Thr231 and Ser404 via increasing protein phosphatase 2A (PP2A) activity and inhibiting glycogen synthase kinase-3β (GSK-3β) activity. Besides, further researches indicated that GJ-4 could inhibit the level of oxidative stress in the brain of OA mice, reduce neuronal apoptosis and inhibit the neuroinflammation mediated by activation of astrocytes in the hippocampus of mice, and eventually achieve its effects in improving learning and memory impairment in mice. According to these findings, we anticipated that GJ-4 might be a potential therapeutic drug for Alzheimer's disease.

Development of Surgical Robots in Recent Years / 中国医疗器械杂志

OBJECTIVE@#To study the development of surgical robots at home and abroad in recent years.@*METHODS@#Through a large number of literature review and analysis, the qualification approval and technical function characteristics of domestic and foreign surgical robots from January 2019 to July 2022 were analyzed.@*RESULTS@#The related situations of 39 surgical robots were analyzed and reported, and the shortcomings and future development direction of the current surgical robots were summarized.@*CONCLUSIONS@#The development of surgical robots in China is now in a rapid development stage. At present, surgical robots generally have the disadvantages of high cost, lack of tactile feedback (force feedback), large size, large space occupation and difficult to move. In the future, it will develop towards intelligent, miniaturized, remote, open and low-cost.

Diversity of bacterial communities in the plasmodia of myxomycetes.

BACKGROUND: Myxomycetes are a group of eukaryotes belonging to Amoebozoa, which are characterized by a distinctive life cycle, including the plasmodium stage and fruit body stage. Plasmodia are all found to be associated with bacteria. However, the information about bacteria diversity and composition in different plasmodia was limited. Therefore, this study aimed to investigate the bacterial diversity of plasmodia from different myxomycetes species and reveal the potential function of plasmodia-associated bacterial communities. RESULTS: The bacterial communities associated with the plasmodia of six myxomycetes (Didymium iridis, Didymium squamulosum, Diderma hemisphaericum, Lepidoderma tigrinum, Fuligo leviderma, and Physarum melleum) were identified by 16S rRNA amplicon sequencing. The six plasmodia harbored 38 to 52 bacterial operational taxonomic units (OTUs) that belonged to 7 phyla, 16 classes, 23 orders, 40 families, and 53 genera. The dominant phyla were Bacteroidetes, Firmicutes, and Proteobacteria. Most OTUs were shared among the six myxomycetes, while unique bacteria in each species only accounted for a tiny proportion of the total OTUs. CONCLUSIONS: Although each of the six myxomycetes plasmodia had different bacterial community compositions, a high similarity was observed in the plasmodia-associated bacterial communities' functional composition. The high enrichment for gram-negative (> 90%) and aerobic (> 99%) bacteria in plasmodia suggest that myxomycetes may positively recruit certain kinds of bacteria from the surrounding environment.

FvWRKY48 binds to the pectate lyase FvPLA promoter to control fruit softening in Fragaria vesca.

The regulatory mechanisms that link WRKY gene expression to fruit ripening are largely unknown. Using transgenic approaches, we showed that a WRKY gene from wild strawberry (Fragaria vesca), FvWRKY48, may be involved in fruit softening and ripening. We showed that FvWRKY48 is localized to the nucleus and that degradation of the pectin cell wall polymer homogalacturonan, which is present in the middle lamella and tricellular junction zones of the fruit, was greater in FvWRKY48-OE (overexpressing) fruits than in empty vector (EV)-transformed fruits and less substantial in FvWRKY48-RNAi (RNA interference) fruits. Transcriptomic analysis indicated that the expression of pectate lyase A (FvPLA) was significantly downregulated in the FvWRKY48-RNAi receptacle. We determined that FvWRKY48 bound to the FvPLA promoter via a W-box element through yeast one-hybrid, electrophoretic mobility shift, and chromatin immunoprecipitation quantitative polymerase chain reaction experiments, and ß-glucosidase activity assays suggested that this binding promotes pectate lyase activity. In addition, softening and pectin degradation were more intense in FvPLA-OE fruit than in EV fruit, and the middle lamella and tricellular junction zones were denser in FvPLA-RNAi fruit than in EV fruit. We speculated that FvWRKY48 maybe increase the expression of FvPLA, resulting in pectin degradation and fruit softening.