Comprehensive analysis and prediction model of mitophagy and ferroptosis in primary immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is linked to specific pathogenic mechanisms, yet its relationship with mitophagy and ferroptosis is poorly understood. This study aimed to identify new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Techniques such as differential analysis, Mfuzz expression pattern clustering, machine learning, gene set enrichment analysis, single-cell RNA sequencing (scRNA-seq) and immune infiltration analysis were employed to investigate the molecular pathways of pivotal genes. Two-sample Mendelian randomization (TSMR) assessed the causal effects in ITP. Key genes identified in the training set included GABARAPL1, S100A8, LIN28A, and GDF9, which demonstrated diagnostic potential in validation sets. Functional analysis indicated these genes' involvement in ubiquitin phosphorylation, PPAR signalling pathway and T-cell differentiation. Immune infiltration analysis revealed increased macrophage presence in ITP, related to the critical genes. scRNA-seq indicated reduced GABARAPL1 expression in ITP bone marrow macrophages. TSMR linked S100A8 with ITP diagnosis, presenting an OR of 0.856 (95% CI = 0.736-0.997, p = 0.045). The study pinpointed four central genes, GABARAPL1, S100A8, LIN28A, and GDF9, tied to mitophagy and ferroptosis in ITP. It posits that diminished GABARAPL1 expression may disrupts ubiquitin phosphorylation and PPAR signalling, impairing mitophagy and inhibiting ferroptosis, leading to immune imbalance.

Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice.

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.

Phospholipase Cγ1 (PLCG1) overexpression is associated with tumor growth and poor survival in IDH wild-type lower-grade gliomas in adult patients.

Gliomas are the most common and recalcitrant intracranial tumors, approximately a quarter of which are classified as lower-grade gliomas (WHO II-III). Although the prognosis of lower-grade gliomas (LGGs) is significantly better than that of higher-grade gliomas, as a highly heterogeneous tumor type, the prognosis of LGGs varies greatly based on the molecular diagnosis. IDH wild-type used to be regarded as a dismal prognostic biomarker in LGGs; however, several studies revealed that IDH wild-type LGGs might not always be equivalent to glioblastoma (WHO IV). Hence, we hypothesize that underlying biological events in LGGs can result in different prognosis. In our study, transcriptome profiling was performed in 24 samples of LGG, and the results showed that the expression of phospholipase Cγ1 (PLCG1) was significantly correlated with IDH1/2 status and patients' clinical outcome. Furthermore, the cancer genome atlas (TCGA) and the Chinese glioma genome atlas (CGGA) databases verified that elevated PLCG1 expression was associated with tumor progression and poor survival in LGG patients. Moreover, PLCG1-targeted siRNA dramatically affected the growth, migration and invasiveness of IDH wild-type LGG cell lines. In in vitro and in vivo experiments, the PLC-targeted drug significantly suppressed the tumor growth of IDH wild-type LGG cell lines in vitro and tumors in mouse models. Taken together, our results demonstrated that higher PLCG1 expression was associated with tumor growth and worse prognosis in IDH wild-type LGGs and PLCG1 could serve as a potential therapeutic target for IDH wild-type LGG patients.

The biogenesis and biological functions of circular RNAs and their molecular diagnostic values in cancers.

BACKGROUND: In addition to non-coding RNAs (lncRNAs) and microRNAs (miRNAs), circular RNAs (circRNAs) are endogenous RNAs with various functions, which have recently become a research hotspot. CircRNAs are a kind of closed circular RNA molecule widely existing in transcriptomes. Due to lack of free ends, they are not easily cleaved by RNase R, thus avoiding degradation. They are more stable than linear RNAs. METHODS: Data were collected through PubMed. The following search terms were used: "circular RNA," "circRNA," "cancer," "mechanism," "biogenesis," "biomarker," "diagnosis." Only articles published in English were included. RESULTS: Most circRNAs express tissue/developmental stage specificity. Moreover, circRNAs are involved in the regulation of a variety of biological activities. In this review, we discuss the formation, classification, and biological functions of circRNAs, especially their molecular diagnostic values in common cancers, including gastric cancer (hsa_circ_002059, circ_LARP4, hsa_circ_0000190, hsa_circ_0000096, circ-SFMBT2, and circ_PVT1), hepatocellular carcinoma (circ_104075, circRNA_100338, circ_MTO1, and circZKSCAN1), colorectal cancer (hsa_circ_0136666 and hsa_circ_0000523), lung cancer (hsa_circ_0006427, circ_100876, and circ_ABCB10), breast cancer (hsa_circ_0089105, circAGFG1, and circEPSTI1), bladder cancer (circFNDC3B and circTFRC), and esophageal squamous cell carcinoma (circ_100876 and circ-DLG1). CONCLUSION: CircRNAs not only play important roles in tumorigenesis, but also may become new diagnostic biomarkers.

Tumor-suppressive circular RNAs: Mechanisms underlying their suppression of tumor occurrence and use as therapeutic targets.

Circular RNAs (circRNAs) have a covalently closed circular conformation and are structurally stable. Those circRNAs with tumor-suppressive properties play an important role in tumorigenesis and metastasis and thus may be used as therapeutic targets of cancers. Herein, we review the current understanding of the classification of circRNAs and summarize the functions and mechanisms of circRNAs that have tumor-suppressive roles in various cancers, including liver cancer (circARSP91, circADAMTS13, circADAMTS14, circMTO1, hsa_circ_0079299, and circC3P1), bladder cancer (circFNDC3B, circITCH, circHIPK3, circRNA-3, cdrlas, and circLPAR1), gastric cancer (circLARP4, circYAP1, hsa_cric_0000096, hsa_circ_0000993, and circPSMC3), breast cancer (circ_000911, hsa_circ_0072309, and circASS1), lung cancer (hsa_circ_0000977, circPTK2, circ_0001649, hsa_circ_100395, and circ_0006916), glioma (circ_0001946, circSHPRH, and circFBXW7), and colorectal cancer (circITGA7 and hsa_circ_0014717). Thanks to their structural stability, these tumor-suppressive circRNAs may be used as potential and potent therapeutic targets. Moreover, we propose a new method for the classification of circRNAs. Based on whether they can be translated, circRNAs can be divided into noncoding circRNAs and coding circRNAs.

Reduced expression of circRNA hsa_circ_0003159 in gastric cancer and its clinical significance.

BACKGROUND: Circular RNAs (circRNAs) play a crucial role in the occurrence of several diseases including cancers. However, little is known about circRNAs' diagnostic values for gastric cancer, one of the worldwide most common diseases of mortality. METHODS: The hsa_circ_0003159 levels in 108 paired gastric cancer tissues and adjacent non-tumorous tissues from surgical patients with gastric cancer were first detected by real-time quantitative reverse transcription-polymerase chain reaction. Then, the relationships between hsa_circ_0003159 expression levels in gastric cancer tissues and the clinicopathological factors of patients with gastric cancer were analyzed. Finally, its diagnostic value was evaluated through the receiver operating characteristic curve. RESULTS: Compared with paired adjacent non-tumorous tissues, hsa_circ_0003159 expression was significantly down-regulated in gastric cancer tissues. What is more, we found that hsa_circ_0003159 expression levels were significantly negatively associated with gender, distal metastasis, and tumor-node-metastasis stage. CONCLUSIONS: All of the results suggest that hsa_circ_0003159 may be a potential cancer marker of patients with gastric cancer.

Clinical values of circular RNA 0000181 in the screening of gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) are recently found involved in cancer occurrence and development. However, their values in the diagnosis of gastric cancers are largely unknown. In this study, we analyzed the values of hsa_circ_0000181 in the diagnosis of gastric cancer. METHODS: Using divergent primers, hsa_circ_0000181 expression levels in fresh gastric cancer tissues and paired adjacent non-tumorous tissues, and plasmas from patient with gastric cancer and health people were detected by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The association between hsa_circ_0000181 levels and the clinicopathologic features of patients with gastric cancer was further analyzed. Finally, to evaluate the diagnostic value, receiver operating characteristic (ROC) curve was established. RESULTS: Hsa_circ_0000181 levels in gastric cancer tissues and plasma from gastric cancer patients were significantly decreased than those in paired adjacent non-tumorous tissues (P < .001) and healthy people (P < .001), respectively. Furthermore, hsa_circ_0000181 expression in gastric cancer tissues was significantly correlated with tumor diameter (P = .027), lymphatic metastasis (P = .044), distal metastasis (P = .023), and carbohydrate antigen 19-9 (P = .031). Its decreased levels in patients' plasma were significantly associated with differentiation (P = .038) and carcinoembryonic antigen (P = .037). The areas under ROC curve were 0.756. The specificity of tissue hsa_circ_0000181 and sensitivity of plasma hsa_circ_0000181 were 85.2% and 99.0%, respectively. CONCLUSIONS: Thanks to the high stability, tissue and plasma hsa_circ_0000181 may be a novel biomarker for the diagnosis of gastric cancer.

2-Trifluoromethyl-2-Hydroxypropionamide Derivatives as Novel Reversal Agents of ABCG2 (BCRP)-Mediated Multidrug Resistance: Synthesis and Biological Evaluations.

It has been postulated that one of the biggest impediments to a successful chemotherapy is the phenomena of multidrug resistance (MDR) in cancer cells. One of the main mechanisms of MDR is overexpression of the ATP-binding cassette (ABC) transporters in cancer cells which alters absorption, distribution, metabolism, and excretion of various chemotherapeutic drugs. Efforts have been made to find effective inhibitors of ABC transporters. However, none has been approved clinically. This study shows that a novel compound 3-chloro-N-(2-hydroxyphenyl)-4-(3,3,3-trifluoro-2-hydroxy-2-methylpropanamido) benzamide (compound 7d), one of the 2-trifluoromethyl-2-hydroxypropionamide derivatives could reverse ABCG2 (BCRP)-mediated MDR. Cytotoxicity studies show that compound 7d sensitizes the ABCG2-overexpressing cells to chemotherapeutic drugs mitoxantrone and SN-38, which are well-established substrates of the ABCG2 transporter. Western blotting results indicate that compound 7d does not significantly alter the protein level of the ABCG2 transporter. Accumulation and efflux studies demonstrate that compound 7d increases intracellular accumulation of mitoxantrone by inhibiting the function of ABCG2. Overall, these findings indicate a potential use for compound 7d as an adjuvant agent for chemotherapy to inhibit the function of the clinically relevant ABC transporter and sensitize tumor cells to chemotherapeutic drugs. J. Cell. Biochem. 118: 2420-2429, 2017. © 2017 Wiley Periodicals, Inc.

Circular RNA 0000096 affects cell growth and migration in gastric cancer.

BACKGROUND: Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. Their role in cancers, especially in gastric cancer, is poorly understood. METHODS: Circular RNA 0000096 (hsa_circ_0000096) levels in 101 paired gastric cancer tissues and adjacent non-tumorous tissues from patients with gastric cancer were detected by real-time quantitative reverse transcription-polymerase chain reaction. A receiver operating characteristic curve was generated to evaluate the diagnostic value of hsa_circ_0000096. RNA interference was used to manipulate the expression of hsa_circ_0000096. Its biological effects were evaluated by flow cytometry, real-time cell analysis, a wound scratch assay, western blot analysis and xenograft models. RESULTS: Hsa_circ_0000096 was found to be significantly downregulated in gastric cancer tissues and gastric cancer cell lines compared with paired adjacent non-tumorous tissues and normal gastric epithelial cells (P<0.001). Moreover, knockdown of hsa_circ_0000096 significantly inhibited cell proliferation and migration in vitro and in vivo. The results of both immunohistochemical and western blot analyses showed that the protein levels of cyclin D1, cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-2 and MMP-9 were significantly reduced in vitro and in vivo. A gastric cancer xenograft nude mouse model indicated that Ki67 and VEGF were reduced in a dose-dependent manner following knockdown of hsa_circ_0000096. However, the expression of E-cadherin increased. CONCLUSIONS: Hsa_circ_0000096 may be used as a potential novel biomarker for gastric cancer. It affects gastric cancer cell growth and migration by regulating cyclin D1, CDK6, MMP-2 and MMP-9.

Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 drug transport.

Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA-1523 (5µM) sensitized the ABCG2 overexpressing cancer cells and ABCG2 transfected cells to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2; also there was no change in the protein expression or the localization of the ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was reversible. Importantly, co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken together, our findings indicate that CCTA-1523 is a potent, selective and reversible modulator of ABCG2 that may offer therapeutic promise for multidrug- resistant malignancies.

Several inaccurate or erroneous conceptions and misleading propaganda about brain-computer interfaces.

Brain-computer interface (BCI) is a revolutionizing human-computer interaction, which has potential applications for specific individuals or groups in specific scenarios. Extensive research has been conducted on the principles and implementation methods of BCI, and efforts are currently being made to bridge the gap from research to real-world applications. However, there are inaccurate or erroneous conceptions about BCI among some members of the public, and certain media outlets, as well as some BCI researchers, developers, manufacturers, and regulators, propagate misleading or overhyped claims about BCI technology. Therefore, this article summarizes the several misconceptions and misleading propaganda about BCI, including BCI being capable of "mind-controlled," "controlling brain," "mind reading," and the ability to "download" or "upload" information from or to the brain using BCI, among others. Finally, the limitations (shortcomings) and limits (boundaries) of BCI, as well as the necessity of conducting research aimed at countering BCI systems are discussed, and several suggestions are offered to reduce misconceptions and misleading claims about BCI.

Comprehensive evaluation methods for translating BCI into practical applications: usability, user satisfaction and usage of online BCI systems.

Although brain-computer interface (BCI) is considered a revolutionary advancement in human-computer interaction and has achieved significant progress, a considerable gap remains between the current technological capabilities and their practical applications. To promote the translation of BCI into practical applications, the gold standard for online evaluation for classification algorithms of BCI has been proposed in some studies. However, few studies have proposed a more comprehensive evaluation method for the entire online BCI system, and it has not yet received sufficient attention from the BCI research and development community. Therefore, the qualitative leap from analyzing and modeling for offline BCI data to the construction of online BCI systems and optimizing their performance is elaborated, and then user-centred is emphasized, and then the comprehensive evaluation methods for translating BCI into practical applications are detailed and reviewed in the article, including the evaluation of the usability (including effectiveness and efficiency of systems), the evaluation of the user satisfaction (including BCI-related aspects, etc.), and the evaluation of the usage (including the match between the system and user, etc.) of online BCI systems. Finally, the challenges faced in the evaluation of the usability and user satisfaction of online BCI systems, the efficacy of online BCI systems, and the integration of BCI and artificial intelligence (AI) and/or virtual reality (VR) and other technologies to enhance the intelligence and user experience of the system are discussed. It is expected that the evaluation methods for online BCI systems elaborated in this review will promote the translation of BCI into practical applications.

Emotion Classification Based on Transformer and CNN for EEG Spatial-Temporal Feature Learning.

OBJECTIVES: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not been fully explored in the classification of emotion-related EEG signals. To address these challenges, the present study proposes a novel model based on transformer and convolutional neural networks (TCNN) for EEG spatial-temporal (EEG ST) feature learning to automatic emotion classification. METHODS: The proposed EEG ST-TCNN model utilizes position encoding (PE) and multi-head attention to perceive channel positions and timing information in EEG signals. Two parallel transformer encoders in the model are used to extract spatial and temporal features from emotion-related EEG signals, and a CNN is used to aggregate the EEG's spatial and temporal features, which are subsequently classified using Softmax. RESULTS: The proposed EEG ST-TCNN model achieved an accuracy of 96.67% on the SEED dataset and accuracies of 95.73%, 96.95%, and 96.34% for the arousal-valence, arousal, and valence dimensions, respectively, for the DEAP dataset. CONCLUSIONS: The results demonstrate the effectiveness of the proposed ST-TCNN model, with superior performance in emotion classification compared to recent relevant studies. SIGNIFICANCE: The proposed EEG ST-TCNN model has the potential to be used for EEG-based automatic emotion recognition.

Considerations and discussions on the clear definition and definite scope of brain-computer interfaces.

Brain-computer interface (BCI) is a revolutionizing human-computer interaction with potential applications in both medical and non-medical fields, emerging as a cutting-edge and trending research direction. Increasing numbers of groups are engaging in BCI research and development. However, in recent years, there has been some confusion regarding BCI, including misleading and hyped propaganda about BCI, and even non-BCI technologies being labeled as BCI. Therefore, a clear definition and a definite scope for BCI are thoroughly considered and discussed in the paper, based on the existing definitions of BCI, including the six key or essential components of BCI. In the review, different from previous definitions of BCI, BCI paradigms and neural coding are explicitly included in the clear definition of BCI provided, and the BCI user (the brain) is clearly identified as a key component of the BCI system. Different people may have different viewpoints on the definition and scope of BCI, as well as some related issues, which are discussed in the article. This review argues that a clear definition and definite scope of BCI will benefit future research and commercial applications. It is hoped that this review will reduce some of the confusion surrounding BCI and promote sustainable development in this field.

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo.

Background: Chimeric antigen receptor T (CAR-T) cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies. However, there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T (CAR-T) cell therapy, as well as the optimal timing for CAR-T cell infusion post-chemotherapy. Materials and Methods: We employed cell-derived tumor xenograft (CDX) murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment. Furthermore, transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen. Results: Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine, followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy, exerts the most efficacious therapeutic effect in B-cell hematological malignancies. Concurrently, RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism, primarily through the inhibition of key mitochondrial targets, such as C-Jun Kinase enzyme (C-JUN). Conclusion: In summary, the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

Synthesized heterogeneous Fenton-like goethite (FeOOH) catalyst for degradation of p-chloronitrobenzene.

The removal of p-chloronitrobenzene (pCNB) was investigated by a heterogeneous Fenton-like system using a laboratory synthesized goethite (FeOOH) as catalyst. The influencing factors and the degradation pathway of pCNB were also evaluated. With a stronger catalytic activity than Fe(2+) catalyst, the synthesized FeOOH catalyst can significantly promote the decomposition of H(2)O(2), and the decomposition product hydroxyl radicals (·OH) can oxidize pCNB in the water effectively. The FeOOH catalyst can also adsorb a certain amount of pCNB, and the adsorption effect is related to the amount of FeOOH and the initial pH value of solution. The results of liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) showed that the main intermediate products were phenolic compounds and carbonyl compounds. About 60% of pCNB was mineralized during the catalytic oxidation, and chlorine and nitro groups on benzene ring were converted into Cl(-) and NO(3)(-) after being attacked.

Age-dependent final size equation to anticipate mortality impact of COVID-19 in China.

Before reopening society in December 2022, China had not achieved sufficiently high vaccination coverage among people aged 80 years and older, who are vulnerable to severe infection and death owing to COVID-19. Suddenly ending the zero-COVID policy was anticipated to lead to substantial mortality. To investigate the mortality impact of COVID-19, we devised an age-dependent transmission model to derive a final size equation, permitting calculation of the expected cumulative incidence. Using an age-specific contact matrix and published estimates of vaccine effectiveness, final size was computed as a function of the basic reproduction number, R0. We also examined hypothetical scenarios in which third-dose vaccination coverage was increased in advance of the epidemic, and also in which mRNA vaccine was used instead of inactivated vaccines. Without additional vaccination, the final size model indicated that a total of 1.4 million deaths (half of which were among people aged 80 years and older) were anticipated with an assumed R0 of 3.4. A 10% increase in third-dose coverage would prevent 30,948, 24,106, and 16,367 deaths, with an assumed second-dose effectiveness of 0%, 10%, and 20%, respectively. With mRNA vaccine, the mortality impact would have been reduced to 1.1 million deaths. The experience of reopening in China indicates the critical importance of balancing pharmaceutical and non-pharmaceutical interventions. Ensuring sufficiently high vaccination coverage is vital in advance of policy changes.

Gene Therapy Strategies Targeting Aging-Related Diseases.

Rapid advancements have taken place in gene therapy technology. However, effective methods for treating aging- or age-related chronic diseases, which are often closely related to genes or even multiple genes, are still lacking. The path to developing cures is winding, while gene therapy that targets genes related to aging represents an exciting research direction with tremendous potential. Among aging-related genes, some candidates have been studied at different levels, from cell to organismal levels (e.g., mammalian models) with different methods, from overexpression to gene editing. The TERT and APOE have even entered the stage of clinical trials. Even those displaying only a preliminary association with diseases have potential applications. This article discusses the foundations and recent breakthroughs in the field of gene therapy, providing a summary of current mainstream strategies and gene therapy products with clinical and preclinical applications. Finally, we review representative target genes and their potential for treating aging or age-related diseases.

Optimization of combustion organization scheme for pre-combustion chamber of pre-cooled engine.

Pre-cooled engines, in which the incoming air is cooled by a pre-cooler before it enters the subsequent components for operation, are one of the important developments in combined power solutions. Therefore, how to optimize the gas temperature uniformity of the high temperature gas stream at the outlet of the pre-combustion chamber to achieve higher efficiency of the pre-cooled engine will be the main research content. In this paper, grid partitioning was performed on the pre combustion chamber model, and the k-omega model and EDC model were used to simulate the internal flow field of the pre combustion chamber. And verify the correctness of the simulation through engine hot testing. Explored the changing trends of the internal velocity and temperature fields of the engine under different secondary injection structures. The larger the secondary injection flow rate, the more obvious the obstruction to high-temperature gas, and the better the uniformity of gas temperature. However, in experiments, the secondary injection components often cannot withstand a large flow rate ratio. Ultimately, the gas temperature uniformity is best when the secondary injection flow rate ratio is 65%. Circumferential deflection will cause the gas to spin, and the spinning process will make the gas temperature at the same radius more uniform. However, due to the decrease in radial velocity, the obstruction effect on the overall high-temperature gas is weakened. When the gas is deflected towards the head by 30°, the velocity of the incoming gas and the velocity of the secondary injection gas are combined and perpendicular to the axis. At this time, the gas temperature uniformity is the best.

Habitual Mask Wearing as Part of COVID-19 Control in Japan: An Assessment Using the Self-Report Habit Index.

Although the Japanese government removed mask-wearing requirements in 2023, relatively high rates of mask wearing have continued in Japan. We aimed to assess psychological reasons and the strength of habitual mask wearing in Japan. An Internet-based cross-sectional survey was conducted with non-random participant recruitment. We explored the frequency of mask usage, investigating psychological reasons for wearing masks. A regression analysis examined the association between psychological reasons and the frequency of mask wearing. The habitual use of masks was assessed in the participant's most frequently visited indoor space and public transport using the self-report habit index. The principal component analysis with varimax rotation revealed distinct habitual characteristics. Among the 2640 participants surveyed from 6 to 9 February 2023, only 4.9% reported not wearing masks at all. Conformity to social norms was the most important reason for masks. Participants exhibited a slightly higher degree of habituation towards mask wearing on public transport compared to indoor spaces. The mask-wearing rate was higher in females than in males, and no significant difference was identified by age group. Daily mask wearing in indoor spaces was characterized by two traits (automaticity and behavioral frequency). A high mask-wearing frequency has been maintained in Japan during the social reopening transition period. Mask wearing has become a part of daily habit, especially on public transport, largely driven by automatic and frequent practice.