Hybrid-Electrolytes System Established by Dual Super-lyophobic Membrane Enabling High-Voltage Aqueous Lithium Metal Batteries.

Aqueous electrolytes and related aqueous rechargeable batteries own unique advantage on safety and environmental friendliness, but coupling high energy density Li-metal batteries with aqueous electrolyte still represent challenging and not yet reported. Here, this work makes a breakthrough in "high-voltage aqueous Li-metal batteries" (HVALMBs) by adopting a brilliant hybrid-electrolytes strategy. Concentrated ternary-salts ether-based electrolyte (CTE) acts as the anolyte to ensure the stability and reversibility of Li-metal plating/stripping. Eco-friendly water-in-salt (WiS) electrolyte acts as catholyte to support the healthy operation of high-voltage cathodes. Most importantly, the aqueous catholyte and non-aqueous anolyte are isolated in each independent chamber without any crosstalk. Aqueous catholyte permeation toward Li anode can be completely prohibited without proton-induced corrosion, which is enabled by the introduction of under-liquid dual super-lyophobic membrane-based separator, which can realize the segregation of the most effective immiscible electrolytes with a surface tension difference as small as 6 mJ m-2. As a result, the aqueous electrolyte can be successfully coupled with Li-metal anode and achieve the fabrication of HVALMBs (hybrid-electrolytes system), which presents long-term cycle stability with a capacity retention of 81.0% after 300 cycles (LiNi0.8Mn0.1Co0.1O2 || Li (limited) cell) and high energy density (682 Wh kg-1).

Frontiers in sarcopenia: Advancements in diagnostics, molecular mechanisms, and therapeutic strategies.

The onset of sarcopenia is intimately linked with aging, posing significant implications not only for individual patient quality of life but also for the broader societal healthcare framework. Early and accurate identification of sarcopenia and a comprehensive understanding of its mechanistic underpinnings and therapeutic targets paramount to addressing this condition effectively. This review endeavors to present a cohesive overview of recent advancements in sarcopenia research and diagnosis. We initially delve into the contemporary diagnostic criteria, specifically referencing the European Working Group on Sarcopenia in Older People (EWGSOP) 2 and Asian Working Group on Sarcopenia (AWGS) 2019 benchmarks. Additionally, we elucidate comprehensive assessment techniques for muscle strength, quantity, and physical performance, highlighting tools such as grip strength, chair stand test, dual-energy X-ray Absorptiometry (DEXA), bioelectrical impedance analysis (BIA), gait speed, and short physical performance battery (SPPB), while also discussing their inherent advantages and limitations. Such diagnostic advancements pave the way for early identification and unequivocal diagnosis of sarcopenia. Proceeding further, we provide a deep-dive into sarcopenia's pathogenesis, offering a thorough examination of associated signaling pathways like the Myostatin, AMP-activated protein kinase (AMPK), insulin/IGF-1 Signaling (IIS), and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Each pathway's role in sarcopenia mediation is detailed, underscoring potential therapeutic target avenues. From a mechanistic perspective, the review also underscores the pivotal role of mitochondrial dysfunction in sarcopenia, emphasizing elements such as mitochondrial oxidative overload, mitochondrial biogenesis, and mitophagy, and highlighting their therapeutic significance. At last, we capture recent strides made in sarcopenia treatment, ranging from nutritional and exercise interventions to potential pharmacological and supplementation strategies. In sum, this review meticulously synthesizes the latest scientific developments in sarcopenia, aiming to enhance diagnostic precision in clinical practice and provide comprehensive insights into refined mechanistic targets and innovative therapeutic interventions, ultimately contributing to optimized patient care and advancements in the field.

Correlational analysis of occupational accidents and the safety policies in the Chinese coal mining industry from 2008 to 2021.

This study investigates the correlation between previous coal mine safety policies and accidents in China. Data on coal mine accidents and government regulatory information from 2008 to 2021 are collected. The characteristics of coal mine accidents are analyzed, and safety policy indexes are identified. An ordinary least squares (OLS) regression model is established to quantitatively analyze the correlation between accidents and safety policy. The study finds that safety policies have some impact on accident occurrence in coal mines. Although there has been a decrease in accidents and deaths over time, higher mortality rates are observed during periods of increased production intensity and on weekends. Gas accidents are the most common, followed by roof and flood accidents. The study concludes that national safety policies with wider coverage and a stronger system are effective in preventing accidents, but caution should be exercised to avoid reduced vigilance with decreasing death rates.

An enhanced multi-attribute crowd evacuation model incorporating the effects of environmental impact factors.

We propose an enhanced floor field model (FFM) to analyze the behavioral characteristics of crowds with varying attributes proportions during evacuation. This model governs pedestrian movement through the Dynamic Floor Field (DFF) and the Static Floor Field (SFF). The DFF takes into account individual factors such as the gender, familiarity with the environment, and social relationships of evacuees, which influence safe evacuation. Concurrently, the SFF encapsulates the impact of environmental factors like obstacles, exits, and guidance effects. Subsequently, this refined FFM was applied and validated using a sports center evacuation scenario. The results demonstrated that the enhanced FFM accurately replicated evacuees' asymmetric behavior and queuing, and aligned well with other models when the number of evacuees fluctuated over time. In the absence of guidance, both environmental familiarity and gender emerged as primary factors influencing partial evacuation. Additionally, the gender of pedestrians significantly affected the overall evacuation. Notably, compared to pre-existing environmental information available to evacuees, the implementation of guidance to augment pedestrians' environmental familiarity resulted in a more efficient evacuation. The FFM model and these findings could be instrumental in simulating personnel evacuation and formulating emergency management strategies in crowded areas.

[Retracted] Isoquercitrin inhibits bladder cancer progression in vitro and in vivo by regulating the PI3K/Akt and PKC signaling pathways.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the agarose gel electrophoretic bands shown in Fig. 4A for PKC were strikingly similar to bands that had already appeared in another article written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 36: 165­172, 2016; DOI: 10.3892/or.2016.4794].

Potential value of mitochondrial regulatory pathways in the clinical application of clear cell renal cell carcinoma: a machine learning-based study.

BACKGROUND: Renal clear cell carcinoma (RCC) is a common cancer in urinary system with increasing incidence. At present, targeted therapy and immunotherapy are the main therapeutic programs in clinical therapy. To develop novel drugs and provide new ideas for clinical therapy, the identification of potential ccRCC subtypes and potential target genes or pathways has become a current research focus. AIM: The aim of this study was to explore the underlying mechanisms of mitochondrial function in ccRCC. This regulatory pathway is closely related to tumor development and metastasis in ccRCC patients, and their abnormal changes may affect the prognosis of cancer patients. Therefore, we decided to construct a prognostic model of ccRCC patients based on mitochondrial regulatory genes, aiming to provide new methods and ideas for clinical therapy. RESULT: The 5-year survival prediction model based on iterative LASSO reached 0.746, and the cox model based on coxph reached C-index = 0.77, integrated c/D AUC = 0.61, and integrated brier score = 0.14. The rsf model based on randomForestSRC was built with C-index = 0.82, integrated c/D AUC = 0.69, and integrated brier score = 0.11. The results show that mitochondrial regulatory pathway is a potential target pathway for clinical therapy of ccRCC, which can provide guidelines for clinical targeted therapy, immunotherapy and other first-line therapy.

The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.

Urologic cancers such as kidney, bladder, prostate, and uroepithelial cancers have recently become a considerable global health burden, and the response to immunotherapy is limited due to immune escape and immune resistance. Therefore, it is crucial to find appropriate and effective combination therapies to improve the sensitivity of patients to immunotherapy. DNA damage repair inhibitors can enhance the immunogenicity of tumor cells by increasing tumor mutational burden and neoantigen expression, activating immune-related signaling pathways, regulating PD-L1 expression, and reversing the immunosuppressive tumor microenvironment to activate the immune system and enhance the efficacy of immunotherapy. Based on promising experimental results from preclinical studies, many clinical trials combining DNA damage repair inhibitors (e.g., PARP inhibitors and ATR inhibitors) with immune checkpoint inhibitors (e.g., PD-1/PD-L1 inhibitors) are underway in patients with urologic cancers. Results from several clinical trials have shown that the combination of DNA damage repair inhibitors with immune checkpoint inhibitors can improve objective rates, progression-free survival, and overall survival (OS) in patients with urologic tumors, especially in patients with defective DNA damage repair genes or a high mutational load. In this review, we present the results of preclinical and clinical trials of different DNA damage repair inhibitors in combination with immune checkpoint inhibitors in urologic cancers and summarize the potential mechanism of action of the combination therapy. Finally, we also discuss the challenges of dose toxicity, biomarker selection, drug tolerance, drug interactions in the treatment of urologic tumors with this combination therapy and look into the future direction of this combination therapy.

Review and prospect of immune checkpoint blockade therapy represented by PD-1/PD-L1 in the treatment of clear cell renal cell carcinoma.

As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma, accounting for approximately 75% of the total number of patients with renal cell carcinoma. Currently, the clinical treatment of ccRCC involves targeted therapy, immunotherapy, and a combination of the two. In immunotherapy, PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment. However, as treatment progresses, some patients gradually develop resistance to immunotherapy. Meanwhile, other patients experience great side effects after immunotherapy, resulting in a survival status far lower than the expected survival rate. Based on these clinical problems, many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results. We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.

Fate of the second task in dual-task interference is associated with sensory system interactions with default-mode network.

Psychological refractory period (PRP) effect refers to the delay in responding to the second of two tasks occurring in rapid succession. While all the major models of PRP highlight the importance of the frontoparietal control network (FPCN) in prioritizing the neural processing of the first task, the fate of the second task remains poorly understood. Here, we provide novel neural evidence on how the functional connectivity between sensory systems and the default-mode network (DMN) suspends the neural processing of the second task to ensure the efficient completion of the first task in dual-task situation. In a cross-modal PRP paradigm, a visual task could either precede or follow an auditory task. The DMN was generally deactivated during task performance and selectively coupled with the sensory system underlying the second task subjected to the PRP effect. Specifically, the DMN showed neural coupling with the auditory system when the auditory task came after the visual task, and with the visual system vice versa. More critically, the strength of the DMN-Sensory coupling correlated negatively with the size of the PRP effect: the stronger the coupling, the shorter the PRP. Therefore, rather than being detrimental to the dual-task performance, temporary suspension of the second task, via the DMN-Sensory coupling, surprisingly guaranteed the efficient completion of the first task by reducing the interference from the second task. Accordingly, the entry and processing of the second stimuli in the central executive system were speeded up as well.

Chemical Synthesis of Innovative Silver Nanohybrids with Synergistically Improved Antimicrobial Properties.

Background: The wide use of antibiotics has created challenges related to antibiotic-resistant bacteria, which have been increasingly found in recent decades. Antibiotic resistance has led to limited choices of antibiotics. Multiple old antimicrobial agents have high antimicrobial properties toward bacteria, but they unfortunately also possess high toxicity toward humans. For instance, silver (Ag) compounds were frequently used to treat tetanus and rheumatism in the 19th century and to treat colds and gonorrhea in the early 20th century. However, the high toxicity of Ag has limited its clinical use. Purpose: We aimed to reformulate Ag to reduce its toxicity toward human cells like osteoblasts and to optimize its antimicrobial properties. Results: Ag, an old antimicrobial agent, was reformulated by hybriding nanomaterials of different dimensions, and silver nanoparticles (AgNPs) of controllable sizes (95-200 nm) and varying shapes (cube, snowflake, and sphere) were synthesized on carbon nanotubes (CNTs). The obtained AgNP-CNT nanohybrids presented significantly higher killing efficacy against Staphylococcus aureus (S. aureus) compared to AgNPs at the same molar concentration and showed synergism in killing S. aureus at 0.2 and 0.4 mM. AgNPs presented significant osteoblast toxicity; in contrast, AgNP-CNT nanohybrids demonstrated significantly enhanced osteoblast viability at 0.04-0.8 mM. The killing of S. aureus by AgNP-CNT nanohybrids was fast, occurring within 15 min. Conclusion: Ag was successfully reformulated and Ag nanohybrids with various AgNP shapes on CNTs were synthesized. The nanohybrids presented significantly enhanced antimicrobial properties and significantly higher osteoblast cell viability compared to AgNPs, showing promise as an innovative antimicrobial nanomaterial for a broad range of biomedical applications.

Numerical Analysis of Fracture Behaviour for Cracked Joints in Corrugated Plate Girders Repaired by Stop-Holes.

The efficient crack eliminated stop-hole measure was proposed to repair and reduce the stress concentration associated fracture risk of the corrugated plate girders by setting it at the critical joint of flange plate with tightened bolts and gaskets under preloading. To investigate the fracture behaviour of these repaired girders, parametric finite element analysis was conducted, focusing on the mechanical feature and stress intensity factor of crack stop-hole in this paper. The numerical model was verified against experimental results first, and then the stress characteristics due to the presence of crack open-hole were analysed. It was found that the moderate-sized open-hole was more effective than the over-sized open-hole in the reduction of stress concentration. For the model with prestressed crack stop-hole through bolt preloading, the stress concentration was nearly 50% with the prestress around open-hole increased to 46 MPa, but such a reduction is inconspicuous for even higher prestress. Relatively high circumferential stress gradients and the crack open angle of oversized crack stop-holes were decreased owing to additional prestress effects from the gasket. Finally, the shift from the original tensile area around the edge of the crack open-hole that was prone to fatigue cracking to a compression-oriented area is beneficial for the reduction of stress intensity factor of the prestressed crack stop-holes. It was also demonstrated that the enlargement of crack open-hole has limited influence on the reduction of stress intensity factor and crack propagation. In contrast, higher bolt prestress was more beneficial in consistently reducing the stress intensity factor of the model with the crack open-hole, even containing long crack.

Coaxial 3D Printing of Zeolite-Based Core-Shell Monolithic Cu-SSZ-13@SiO2 Catalysts for Diesel Exhaust Treatment.

Core-shell catalysts with functional shells can increase the activity and stability of the catalysts in selective catalytic reduction of NOx with ammoniax . However, the conventional approaches based on multistep fabrication for core-shell structures encounter persistent restrictions regarding strict synthesis conditions and limited design flexibility. Herein, a facile coaxial 3D printing strategy is for the first time developed to construct zeolite-based core-shell monolithic catalysts with interconnected honeycomb structures, in which the hydrophilic noncompact silica serves as shell and Cu-SSZ-13 zeolite acts as core. Compared to a Cu-SSZ-13 monolith which suffers from the interfacial diffusion, the SiO2 shell layer can increase the accessibility of active sites over Cu-SSZ-13@SiO2 , resulting in a 10-20% higher NO conversion at200-550 °C under 300 000 cm3 g-1 h-1 . Meanwhile, a thicker SiO2 shell enhances the hydrothermal stability of the aged catalyst by inhibiting the dealumination and the formation of CuOx . Other representative monolithic catalysts with different topological zeolites as shell and diverse metal oxides as the core can be also realized by this coaxial 3D printing. This strategy allows multiple porous materials to be directly integrated, which allows for flexible design and fabrication of various core-shell monolithic catalysts with customized functionalities.

FIPRESCI: droplet microfluidics based combinatorial indexing for massive-scale 5'-end single-cell RNA sequencing.

Single-cell RNA sequencing methods focusing on the 5'-end of transcripts can reveal promoter and enhancer activity and efficiently profile immune receptor repertoire. However, ultra-high-throughput 5'-end single-cell RNA sequencing methods have not been described. We introduce FIPRESCI, 5'-end single-cell combinatorial indexing RNA-Seq, enabling massive sample multiplexing and increasing the throughput of the droplet microfluidics system by over tenfold. We demonstrate FIPRESCI enables the generation of approximately 100,000 single-cell transcriptomes from E10.5 whole mouse embryos in a single-channel experiment, and simultaneous identification of subpopulation differences and T cell receptor signatures of peripheral blood T cells from 12 cancer patients.

Research on the Characteristics of Safety Culture and Obstacle Factors among Residents under the Influence of COVID-19 in China.

This study established a comprehensive evaluation indicator model for the safety culture among residents during COVID-19 and an obstacle degree model for the identification of the major factors affecting the residents' safety culture. The results show that the overall level of the safety culture among residents was 0.6059. Safety education, channels for learning knowledge regarding safety, and implementation of safety management systems are currently the major obstacles affecting safety culture among residents, but there is still space for improvement in the future. Furthermore, the level of safety culture was strongly related to the distance from the infected, because this changes the risk of viral infection. There are also differences in obstacle factors in different regions. Therefore, it is necessary to implement measures targeting the improvement of safety culture in accordance with the risk of viral infection. Strategies for strengthening the safety culture are also given in this study for consideration in strategic decision making with the aim of promoting the improvement of safety culture among residents, which may help to reduce the risk of infection with COVID-19 for residents.

Targeting the Glycolytic Enzyme PGK1 to Inhibit the Warburg Effect: A New Strategy for Keloid Therapy.

BACKGROUND: Aerobic glycolysis (the Warburg effect) may play an important role in keloid pathogenesis, which may be aggravated by the hypoxic microenvironment in keloids. Phosphoglycerate kinase 1 (PGK1), a key glycolytic enzyme, is essential for cellular aerobic glycolysis, but its role in keloid formation remains unknown. This study aimed to detect PGK1 expression in keloid tissue and investigate the effects of inhibiting PGK1 expression on keloid fibroblasts (KFbs) under hypoxia and normoxia. METHODS: Normal skin and keloid samples were separated into two parts, one was used for immunohistochemistry, and one for primary cell culture. PGK1 tissue expression was detected by immunohistochemistry. Reverse-transcriptase polymerase chain reaction and Western blotting were used to detect PGK1, GLUT1, LDHA, and COL1 expression, and glucose uptake and lactate production were detected with a microplate reader. Cell proliferation and apoptosis were investigated with IncuCyte and flow cytometry. Cell migration and invasion were detected with Transwell assays. Glycolytic function was explored with the Seahorse XF96 system. RESULTS: Immunohistochemistry showed PGK1 overexpression in keloid tissue compared with normal skin tissue ( P < 0.05). Consistently, PGK1 expression was significantly higher in KFbs than in normal skin fibroblasts (NFbs), and hypoxia stimulated PGK1 expression in KFbs and NFbs ( P < 0.05). PGK1 knockdown significantly inhibited KFb glycolysis, proliferation, migration, invasion, glucose consumption, and lactate production ( P < 0.05). Furthermore, GLUT1, LDHA, and COL1 expression was decreased in KFbs compared with NFbs ( P < 0.05). In addition, suppressing PGK1 may mediate the PI3K/AKT pathway to down-regulate GLUT1, LDHA, and COL1 expression ( P < 0.05). CONCLUSIONS: These findings provide new evidence that suppressing PGK1, inhibiting glycolysis, reduces KFb proliferation, migration, invasion, and type I collagen expression. Targeting PGK1 to inhibit the Warburg effect may be a new therapeutic strategy for keloids. CLINICAL RELEVANCE STATEMENT: This article may provide new suggestions into the pathogenesis and treatment of keloids. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Anti-Inflammatory Effects of the 35kDa Hyaluronic Acid Fragment (B-HA/HA35).

Background: Hyaluronic acid (HA) and HA fragments interact with a variety of human body receptors and are involved in the regulation of various physiological functions and leukocyte trafficking in the body. Accordingly, the development of an injectable HA fragment with good tissue permeability, the identification of its indications, and molecular mechanisms are of great significance for its clinical application. The previous studies showed that the clinical effects of injectable 35kDa B-HA result from B-HA binding to multiple receptors in different cells, tissues, and organs. This study lays the foundation for further studies on the comprehensive clinical effects of injectable B-HA. Methods: We elaborated on the production process, bioactivity assay, efficacy analyses, and safety evaluation of an injectable novel HA fragment with an average molecular weight of 35 kDa (35 kDa B-HA), produced by recombinant human hyaluronidase PH20 digestion. Results: The results showed that 35 kDa B-HA induced human erythrocyte aggregation (rouleaux formation) and accelerated erythrocyte sedimentation rates through the CD44 receptor. B-HA application and injection treatment significantly promoted the removal of mononuclear cells from the site of inflammation and into the lymphatic circulation. At a low concentration, 35 kDa B-HA inhibited production of reactive oxygen species and tumor necrosis factor by neutrophils; at a higher concentration, 35 kDa B-HA promoted the migration of monocytes. Furthermore, 35 kDa B-HA significantly inhibited the migration of neutrophils with or without lipopolysaccharide treatment, suggesting that in local tissues, higher concentrations of 35 kDa B-HA have antiinflammatory effects. After 99mTc radiolabeled 35 kDa B-HA was intravenously injected into mice, it quickly entered into the spleen, liver, lungs, kidneys and other organs through the blood circulation. Conclusion: This study demonstrated that the HA fragment B-HA has good tissue permeability and antiinflammatory effects, laying a theoretical foundation for further clinical studies.

PI3K/AKT pathway promotes keloid fibroblasts proliferation by enhancing glycolysis under hypoxia.

Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains unclear. Here, we show that when PI3K/AKT pathway was inactivated with LY294002, the protein expression of glycolytic enzymes decreased, while the amount of mitochondria and mitochondrial membrane potential increased. The key parameters of extracellular acidification rate markedly diminished, and those of oxygen consumption rate significantly increased after inhibition of the PI3K/AKT pathway. When the PI3K/AKT pathway was suppressed, the levels of reactive oxygen species (ROS) and mitochondrial ROS (mitoROS) were significantly increased. Meanwhile, cell proliferation, migration and invasion were inhibited, and apoptosis was increased when the PI3K/AKT pathway was blocked. Additionally, cell proliferation was compromised when KFb were treated with both SC79 (an activator of the PI3K/AKT pathway) and 2-deoxy-d-glucose (an inhibitor of glycolysis), compared with the SC79 group. Moreover, a positive feedback mechanism was demonstrated between the PI3K/AKT pathway and hypoxia-inducible factor-1α (HIF-1α). Our data collectively demonstrated that the PI3K/AKT pathway promotes proliferation and inhibits apoptosis in KFb under hypoxia by regulating glycolysis, indicating that the PI3K/AKT signalling pathway could be a therapeutic target for keloids.

Detection of consensus genomic regions and candidate genes for quality traits in barley using QTL meta-analysis.

Improving barley grain quality is a major goal in barley breeding. In this study, a total of 35 papers focusing on quantitative trait loci (QTLs) mapping for barley quality traits published since 2000 were collected. Among the 454 QTLs identified in these studies, 349 of them were mapped onto high-density consensus maps, which were used for QTL meta-analysis. Through QTL meta-analysis, the initial QTLs were integrated into 41 meta-QTLs (MQTLs) with an average confidence interval (CI) of 1. 66 cM, which is 88.9% narrower than that of the initial QTLs. Among the 41 identified MQTLs, 25 were subsequently validated in publications using genome-wide association study (GWAS). From these 25 validated MQTLs, ten breeder's MQTLs were selected. Synteny analysis comparing barley and wheat MQTLs revealed orthologous relationships between eight breeder's MQTLs and 45 wheat MQTLs. Additionally, 17 barley homologs associated with rice quality traits were identified within the regions of the breeder's MQTLs through comparative analysis. The findings of this study provide valuable insights for molecular marker-assisted breeding and the identification of candidate genes related to quality traits in barley.