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Abstract Microflow catalysis is a cutting-edge approach to advancing chemical synthesis and manufacturing, but the challenge lies in developing efficient and stable multiphase catalysts. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through covalent bonds, enabling highly continuous flow catalysis. Two Fe4L4 tetrahedral cages bearing four uncoordinated amines were designed and synthesized. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane, introducing silane chains immobilized on the inner walls of the microfluidic reactor. The immobilized cages prove highly efficient for the reaction of anthranilamide with aldehydes, showing superior reactivity and recyclability relative to free cages. This superiority arises from the large cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and the potential for future automated synthesis processes

Abstract Background The attentional network test (ANT) is widely used to evaluate the performance of three attentional networks: alerting, orienting and executive attention networks. This study aimed to investigate the characteristics of attention functions in HIV-negative patients with early forms of neurosyphilis (NS) and their correlation with abnormalities in brain magnetic resonance imaging (MRI). Methods Thirty patients with early forms of NS, 31 patients with syphilis but without NS (Non-NS) and 35 healthy controls were recruited from an HIV-negative cohort between September 2020 and November 2022. The participants were evaluated with the ANT and the Mini-Mental State Examination (MMSE). Brain MRI was performed in NS and Non-NS patients. Results No significant differences were observed in the MMSE scores among the three groups. However, patients with early forms of NS showed poorer performance in orienting and alerting functions than Non-NS group (F = 6.952, P = 0.011 and F = 8.794, P = 0.004, respectively); No significant difference was observed in executive function between the two groups (F = 0.001, P = 0.980). Multivariate analysis of variance using the Bonferroni post hoc test indicated that patients with NS exhibited less efficient orienting function (P = 0.023), and alerting function (P = 0.003) but not executive function (P = 0.99), compared to Non-NS patients. Additionally, a significant difference was found in orienting function between patients with NS and healthy controls (P

The main aim of this research is to study the influence of traditional, online, and hybrid teaching modes on student academic performance. For this purpose, three determinants of perceived satisfaction and academic performance are used to compare student learning outcomes across the different teaching mediums. This is the first study to examine different teaching modes and their influence on students enrolled in higher education institutions. The study context is a set of China’s higher education sector after the COVID-19 outbreak. Data were collected on the model variables through an online questionnaire and distributed amongst a sample of undergraduate students who were enrolled at Overseas Education College at Jiangsu University. Data collection was divided into three categories: pre-pandemic, pandemic, and endemic situations in China. Structural equation modelling technique was adopted to inspect the collected data and confirm the hypothesis. Results show that student learning and student expectations have a significant positive impact on student perceived satisfaction in all contexts. Moreover, online mode of teaching yielded higher level of student satisfaction and hence, their academic performance. Findings of this study have generated implications for stakeholders of the education sector. Teachers must consistently improve themselves in terms of knowledge and skills, while the ministry of education should set required standards and monitor compliance. They should make some courses related to technology and innovation as a part of the undergraduate syllabus. These will help to stay relevant in today’s competitive academic sector.

Lung cancer is still the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the main pathological type of lung cancer, accounting for about 80%. Approximately 30% of all patients with NSCLC have resectable early and middle stage disease at the time of diagnosis. Recently, the epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have made a major breakthrough in the adjuvant targeted therapy of EGFR-mutated resectable NSCLC, and are recommended by the guidelines for clinical use. In this review, we summarize the clinical research progress of perioperative adjuvant targeted therapy for EGFR-mutated resectable NSCLC, and discuss the key issues in the clinical researches.

Abstract Background With the increasing incidence of steroid-induced necrosis of the femoral head (SNFH), numerous scholars have investigated its pathogenesis. Current evidence suggests that the imbalance between lipogenesis and osteoblast differentiation in bone marrow mesenchymal stem cells (BMSCs) is a key pathological feature of SNFH. MicroRNAs (miRNAs) have strong gene regulatory effects and can influence the direction of cell differentiation. N6-methyladenosine (m6A) is a prevalent epigenetic modification involved in diverse pathophysiological processes. However, knowledge of how miRNAs regulate m6A-related factors that affect BMSC differentiation is limited. Objective We aimed to investigate the role of miR27a in regulating the expression of YTHDF2 in BMSCs. Methods We compared miR27a, YTHDF2, and total m6A mRNA levels in SNFH-affected and control BMSCs. CCK-8 and TUNEL assays were used to assess BMSC proliferation and apoptosis. Western blotting and qRT‒PCR were used to measure the expression of osteogenic (ALP, RUNX2, and OCN) and lipogenic (PPARγ and C/EBPα) markers. Alizarin Red and Oil Red O staining were used to quantify osteogenic and lipogenic differentiation, respectively. miR27a was knocked down or overexpressed to evaluate its impact on BMSC differentiation and its relationship with YTHDF2. Bioinformatics analyses identified YTHDF2 as a differentially expressed gene in SNFH (ROC analysis) and revealed potential signaling pathways through GSEA. The effects of YTHDF2 silencing on the lipogenic and osteogenic functions of BMSCs were assessed. Results miR27a downregulation and YTHDF2 upregulation were observed in the SNFH BMSCs. miR27a knockdown/overexpression modulated YTHDF2 expression, impacting BMSC differentiation. miR27a silencing decreased m6A methylation and promoted osteogenic differentiation, while YTHDF2 silencing exerted similar effects. GSEA suggested potential signaling pathways associated with YTHDF2 in SNFH. Conclusion miR27a regulates BMSC differentiation through YTHDF2, affecting m6A methylation and promoting osteogenesis. This finding suggests a potential therapeutic target for SNFH.

Abstract Background Fatty liver hemorrhagic syndrome (FLHS) in the modern poultry industry is primarily caused by nutrition. Despite encouraging progress on FLHS, the mechanism through which nutrition influences susceptibility to FLHS is still lacking in terms of epigenetics. Results In this study, we analyzed the genome-wide patterns of trimethylated lysine residue 27 of histone H3 (H3K27me3) enrichment by chromatin immunoprecipitation-sequencing (ChIP-seq), and examined its association with transcriptomes in healthy and FLHS hens. The study results indicated that H3K27me3 levels were increased in the FLHS hens on a genome-wide scale. Additionally, H3K27me3 was found to occupy the entire gene and the distant intergenic region, which may function as silencer-like regulatory elements. The analysis of transcription factor (TF) motifs in hypermethylated peaks has demonstrated that 23 TFs are involved in the regulation of liver metabolism and development. Transcriptomic analysis indicated that differentially expressed genes (DEGs) were enriched in fatty acid metabolism, amino acid, and carbohydrate metabolism. The hub gene identified from PPI network is fatty acid synthase (FASN). Combined ChIP-seq and transcriptome analysis revealed that the increased H3K27me3 and down-regulated genes have significant enrichment in the ECM-receptor interaction, tight junction, cell adhesion molecules, adherens junction, and TGF-beta signaling pathways. Conclusions Overall, the trimethylation modification of H3K27 has been shown to have significant regulatory function in FLHS, mediating the expression of crucial genes associated with the ECM-receptor interaction pathway. This highlights the epigenetic mechanisms of H3K27me3 and provides insights into exploring core regulatory targets and nutritional regulation strategies in FLHS.

ABSTRACT: Most of follicles undergo a degenerative process called follicular atresia. This process directly affects the egg production of laying hens and is regulated by external and internal factors. External factors primarily include nutrition and environmental factors. In follicular atresia, internal factors are predominantly regulated at 3 levels; organic, cellular and molecular levels. At the organic level, the hypothalamic-pituitary-ovary (HPO) axis plays an essential role in controlling follicular development. At the cellular level, gonadotropins and cytokines, as well as estrogens, bind to their receptors and activate different signaling pathways, thereby suppressing follicular atresia. By contrast, oxidative stress induces follicular atresia by increasing ROS levels. At the molecular level, granulosa cell (GC) apoptosis is not the only factor triggering follicular atresia. Autophagy is also known to give rise to atresia. Epigenetics also plays a pivotal role in regulating gene expression in processes that seem to be related to follicular atresia, such as apoptosis, autophagy, proliferation, and steroidogenesis. Among these processes, the miRNA regulation mechanism is well-studied. The current review focuses on factors that regulate follicular atresia at organic, cellular and molecular levels and evaluates the interaction network among these levels. Additionally, this review summarizes atretic follicle characteristics, in vitro modeling methods, and factors preventing follicular atresia in laying hens.

In recent years, with the increased usage of tumour necrosis factor (TNF) inhibitors, more side effects have been revealed. Paradoxical psoriasis, including psoriasis vulgaris, palmoplantar pustulosis, scalp psoriasis and their combinations, is a common adverse effect. However, erythrodermic psoriasis associated with alopecia due to anti-TNF-α is rarely reported in the literature. We report a 44-year-old woman who developed erythrodermic psoriasis associated with diffuse alopecia during her treatment with adalimumab for palmoplantar pustulosis.

Abstract Despite the large public health toll of smoking, genetic studies of smoking cessation have been limited with few discoveries of risk or protective loci. We investigated common and rare variant associations with success in quitting smoking using a cohort from 8 randomized controlled trials involving 2231 participants and a total of 10,020 common and 24,147 rare variants. We identified 14 novel markers including 6 mapping to genes previously related to psychiatric and substance use disorders, 4 of which were protective (CYP2B6 (rs1175607105), HTR3B (rs1413172952; rs1204720503), rs80210037 on chr15), and 2 of which were associated with reduced cessation (PARP15 (rs2173763), SCL18A2 (rs363222)). The others mapped to areas associated with cancer including FOXP1 (rs1288980) and ZEB1 (rs7349). Network analysis identified significant canonical pathways for the serotonin receptor signaling pathway, nicotine and bupropion metabolism, and several related to tumor suppression. Two novel markers (rs6749438; rs6718083) on chr2 are flanked by genes associated with regulation of bodyweight. The identification of novel loci in this study can provide new targets of pharmacotherapy and inform efforts to develop personalized treatments based on genetic profiles.

Abstract Considering the cooperative willingness of multiple heterogeneous energy sources to participate in the alliance, the stability of the cooperative operation of each entity (hereinafter referred to as stability) and the supporting mechanism of its optimal combination to realize the high proportion of new energy generation are studied. Through simulating load peak‐cutting and valley‐filling in the power system, the difference between the load value and the base load in the 24 h of the daily load curve is used as the calculation condition for the supply balance of the alliance. Based on the source‐load power balance model, the feasibility of power data normalization is derived and demonstrated. Simultaneously, taking into account the time‐of‐use price cost of each entity, a multiscale operation cost allocation and stability evolution analysis model for the alliance is constructed using the Shapley value and the largest consistent set method. By comparing the willingness of each entity to engage in the alliance, as well as the multiscale operation stability and economic change rule of different alliances, the results demonstrate that: (1) Alliance 1 has the advantage of economic operation. (2) The common stability period of different alliances is influenced by the participation preferences of each entity (wind power, photovoltaic, and thermal power tend to participate in Alliance 1, while hydropower tends to participate in Alliance 2). (3) Alliance internal restructuring can be carried out by utilizing spatial and temporal difference characteristics of different entities’ participation in alliance preferences, thereby achieving alliance stability and efficient operation. This study provides a theoretical basis for making decisions regarding the optimized stable operation of the alliance.

Abstract Background Numerous studies have characterized the gut microbiome (GM) in lung cancer (LC). Yet, the causality between GM and LC and its subtypes remain uncharacterized. Methods Two‐sample Mendelian randomization (MR) was designed to investigate the causal relationship between the GM and LC and its subtypes, using publicly available summary data of genome‐wide association studies. The researchers ran two groups of MR analyses, including the genome‐wide statistical significance threshold (5 × 10−8) and the locus‐wide significance level (1 × 10−5). Results Using MR analysis, we ascertained 42 groups of GM that are intimately linked to LC and its subtypes at the locus‐wide significance level. Of the 42 groups, 12 were in LC, nine in non‐small cell lung cancer (NSCLC), six in small cell lung cancer (SCLC), two in lung adenocarcinomas, and 13 in lung squamous carcinomas. After false discovery rate correction, we still found a remarkable causal interaction between the Eubacterium ruminantium group and SCLC. Moreover, five groups of GM closely linked to LC and its subtypes were recognised at the genome‐wide statistical significance threshold. This finding included one group each in LC, NSCLC and SCLC, two groups in lung adenocarcinoma and none in lung squamous carcinoma. None of the foregoing findings were heterogeneous or horizontal pleiotropy. Reverse MR revealed that genetic susceptibility to LC and its subtypes caused significant changes in three groups of GM. Conclusion Our findings substantiate the causality between GM and LC and its subtypes. This study offers fresh insights into the function of GM in mediating the progression of LC.

Abstract. Background:. Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods:. Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment. Results:. Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth (t = 9.917, P

Physical separation of acetylene (C2H2) from carbon dioxide (CO2) or ethylene (C2H4) on metal–organic frameworks (MOFs) is crucial for achieving high-purity feed gases with minimal energy penalty. However, such processes are exceptionally challenging due to their close physical properties and are also critically restricted by the high cost of large-scale MOF synthesis. Here, we demonstrate the readily scalable synthesis of a highly water-resistant chiral Cu-MOF (TAMOF-1) based on an inexpensive proteogenic amino acid derivative bearing rich N/O sites. Notably, the unique coordination in this ultramicroporous MOF has resulted in the generation of rare global negative electrostatic potentials, which greatly facilitate the electrostatic interactions with C2H2 molecules, thus leading to their efficient separation from C2H2/CO2 and C2H2/C2H4 mixtures under ambient conditions. The separation efficiency and mechanism are unequivocally validated by breakthrough experiments and computational simulations. This work not only highlights the pivotal role of creating a negative electro-environment in confined spaces for boosting C2H2 capture and separation but also opens up new ways of employing cheap amino acid derivatives bearing rich electro-negative N and O sites as organic linkers to constructing high-performing MOF materials for gas separation purposes.

Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc – a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively – and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.

MiT family translocation renal cell carcinomas (tRCCs) primarily include Xp11.2/transcription factor E3 (TFE3) gene fusion-associated renal cell carcinoma (Xp11.2 tRCC) and t(6;11)/TFEB gene fusion-associated RCC. Clinical cases of these carcinomas are rare. Fluorescence in situ hybridization can be used to identify the type, but there are no standard diagnostic and treatment methods available, and the prognosis remains controversial. Herein, we present a case of a patient with Xp11.2 tRCC at 29 weeks of gestation. The baby was successfully delivered, and radical surgery was performed for renal cancer at the same time. This is a unique and extremely rare case. We have described the case and performed a literature review to report the progress of current research on the treatment and prognosis of pregnant patients with Xp11.2/TFE3 translocation renal cell carcinoma. This study aims to contribute to improving the diagnosis and treatment of Xp11.2 tRCC in pregnant patients.

IntroductionA total of 94 Propionibacterium acnes (P. acnes) isolates were obtained from a hospital in Beijing to evaluate their susceptibility to erythromycin, clarithromycin, doxycycline, and minocycline. As well as the determination of the effectiveness of P. acnes phages in vitro and in P. acnes-induced lesions mouse model.MethodsPatients with acne vulgaris (AV) were enrolled from August 2021 to October 2022. Standard methods were employed for specimen collection, culture, and identification of P. acnes. Susceptibility testing was conducted using E-strips for erythromycin, clarithromycin, minocycline, and doxycycline. Phage culture and identification followed standard procedures. A mouse model with P. acnes-induced skin lesions was established, and data was analyzed using χ2 test.ResultsThe results showed that all isolates were susceptible to minocycline and doxycycline, while 53 (56.4%) and 52 (55.3%) isolates were susceptible to erythromycin and clarithromycin, respectively. Interestingly, younger patients and those with lower acne severity exhibited reduced resistance. Phage cleavage rates ranged from 88.30 to 93.60%. Multilocus sequence typing (MLST) analysis was conducted on eight randomly selected P. acnes isolates, and the IA-2 subtype was used in experiments to address P. acnes-induced lesions in mice. Phage therapy proved effective in this model.DiscussionThis study highlights the high susceptibility of P. acnes to doxycycline and tetracycline, while erythromycin and clarithromycin exhibited elevated resistance. Additionally, P. acnes phages demonstrated high cleavage rates and potential effectiveness in treating P. acnes-induced lesions. These findings suggest promising avenues for further exploration of phage therapy in acne treatment.

Styxl2, a poorly characterized pseudophosphatase, was identified as a transcriptional target of the Jak1-Stat1 pathway during myoblast differentiation in culture. Styxl2 is specifically expressed in vertebrate striated muscles. By gene knockdown in zebrafish or genetic knockout in mice, we found that Styxl2 plays an essential role in maintaining sarcomere integrity in developing muscles. To further reveal the functions of Styxl2 in adult muscles, we generated two inducible knockout mouse models: one with Styxl2 being deleted in mature myofibers to assess its role in sarcomere maintenance, and the other in adult muscle satellite cells (MuSCs) to assess its role in de novo sarcomere assembly. We find that Styxl2 is not required for sarcomere maintenance but functions in de novo sarcomere assembly during injury-induced muscle regeneration. Mechanistically, Styxl2 interacts with non-muscle myosin IIs, enhances their ubiquitination, and targets them for autophagy-dependent degradation. Without Styxl2, the degradation of non-muscle myosin IIs is delayed, which leads to defective sarcomere assembly and force generation. Thus, Styxl2 promotes de novo sarcomere assembly by interacting with non-muscle myosin IIs and facilitating their autophagic degradation.

BackgroundSLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.MethodsWe collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.ResultsElevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.ConclusionOur study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.

Abstract Hereditary deafness is a common neurosensory disorder, and 148 non‐syndromic deafness genes have been identified to date. Gene therapy has been used to treat a variety of genetic diseases, but no gene therapy drug for hereditary deafness has been approved for clinical use. At present, several clinical trials of gene therapy for hereditary deafness are underway. However, few normative documents have been issued to guide the standardization of gene therapy for hearing loss, and this document is the first global gene therapy guideline for hereditary hearing loss. The guidelines were jointly developed and drafted by experienced audiologists, virologists and biologists who are vigorously involved in inner ear gene therapy research in the Hearing, Speech and Communication Subsociety of Biophysical Society of China, Audiology Development Foundation Of China and Audiology Subsociety of Jiangsu Medical Association. These guidelines cover preclinical research and clinical practice of gene therapy for hereditary deafness, including indications, key points of pre‐clinical research, patient selection criteria, pre‐clinical preparation, drug efficacy, drug safety evaluation criteria, ethical review, etc. We hope that the guidelines will promote the standardization of clinical practice related to gene therapy for hereditary deafness in China and around the world.

BackgroundTemozolomide (TMZ) is a key component in the treatment of gliomas. Hypermutation induced by TMZ can be encountered in routine clinical practice, and its significance is progressively gaining recognition. However, the relationship between TMZ-induced hypermutation and the immunologic response remains controversial.Case presentationWe present the case of a 38-year-old male patient who underwent five surgeries for glioma. Initially diagnosed with IDH-mutant astrocytoma (WHO grade 2) during the first two surgeries, the disease progressed to grade 4 in subsequent interventions. Prior to the fourth surgery, the patient received 3 cycles of standard TMZ chemotherapy and 9 cycles of dose-dense TMZ regimens. Genomic and immunologic analyses of the tumor tissue obtained during the fourth surgery revealed a relatively favorable immune microenvironment, as indicated by an immunophenoscore of 5, suggesting potential benefits from immunotherapy. Consequently, the patient underwent low-dose irradiation combined with immunoadjuvant treatment. After completing 4 cycles of immunotherapy, the tumor significantly shrank, resulting in a partial response. However, after a 6-month duration of response, the patient experienced disease progression. Subsequent analysis of the tumor tissue obtained during the fifth surgery revealed the occurrence of hypermutation, with mutation signature analysis attributing TMZ treatment as the primary cause. Unfortunately, the patient succumbed shortly thereafter, with a survival period of 126 months.ConclusionPatients subjected to a prolonged regimen of TMZ treatment may exhibit heightened vulnerability to hypermutation. This hypermutation induced by TMZ holds the potential to function as an indicator associated with unfavorable response to immunotherapy in gliomas.

PurposeDysregulated expression of microRNA (miRNAs) in lung cancer has been wildly reported. The clinicopathologic significance of miR-9-5p in non-small-cell lung cancer (NSCLC) patients and its effect on NSCLC progression were explored in this study.Patients and methodsA total of 76 NSCLC patients were included. miR-9-5p expression was evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Then, in vitro experiments including cell growth curve assays, colony formation assays, and transwell migration assays were performed. Further clinicopathological and prognostic values were explored using bioinformatics analysis of the TCGA database.ResultsmiR-9-5p expression was significantly increased in tumor tissues (both P < 0.0001). miR-9-5p expression was relatively higher in larger tumors (P = 0.0327) and in lung squamous carcinoma (LUSC) (P = 0. 0143). In addition, miR-9-5p was significantly upregulated in the normal lung tissues of cigarette smokers (P = 0.0099). In vitro, miR-9-5p was correlated with cell proliferation and migration. After that, bioinformatics analysis of the TCGA database indicated that miR-9-5p was correlated with tumor size (P = 0.0022), lymphatic metastasis (P = 0.0141), LUSC (P < 0.0001), and smoking history (P < 0.0001). Finally, a prognostic study indicated high miR-9-5p expression was correlated with poor prognosis in LUAD (P = 0.0121).ConclusionUpregulation of miR-9-5p may have an oncogenic effect in NSCLC and may be related to smoking. The conclusion of this study may help find new prognostic and therapeutic targets for NSCLC and the exploration of the relationship between smoking and lung cancer.

Abstract. Background:. Observational research has reported that systemic lupus erythematosus (SLE) is related to common female hormone-dependent cancers, but the underlying causal effect remains undefined. This study aimed to explore the causal association of these conditions by Mendelian randomization (MR) analysis. Methods:. We selected instrumental variables for SLE from genome-wide association studies (GWASs) conducted in European and East Asian populations. The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs. We utilized inverse variance weighted (IVW) as the primary analysis, followed by sensitivity analysis. Furthermore, we conducted multivariable MR (MVMR) to estimate direct effects by adjusting for the body mass index and estradiol. Finally, we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results. Results:. We found SLE was significantly negatively associated with overall endometrial cancer risk (odds ratio [OR] = 0.961, 95% confidence interval [CI] = 0.935–0.987, P = 3.57E−03) and moderately inversely related to endometrioid endometrial cancer (ENEC) (OR = 0.965, 95% CI = 0.936–0.995, P = 0.024) risk in the European population by IVW. We replicated these results using other MR models and detected a direct effect by MVMR (overall endometrial cancer, OR = 0.962, 95% CI = 0.941–0.983, P = 5.11E−04; ENEC, OR = 0.964, 95% CI = 0.940–0.989, P = 0.005). Moreover, we revealed that SLE was correlated with decreased breast cancer risk (OR = 0.951, 95% CI = 0.918–0.986, P = 0.006) in the East Asian population by IVW, and the effect was still significant in MVMR (OR = 0.934, 95% CI = 0.859–0.976, P = 0.002). The statistical powers of positive MR results were all >0.9. Conclusion:. This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations, respectively, by MR analysis, which compensates for inherent limitations of observational research.

The damage characteristics of fused silica were investigated under low-temporal coherence light (LTCL). It was found that the laser-induced damage threshold (LIDT) of fused silica for the LTCL was lower than that of the single longitudinal mode pulse laser, and for the LTCLs, the LIDTs decrease with the increasing of laser bandwidth, which is not consistent with the temporal spike intensity. This is due to the nonlinear self-focusing effect and multi-pulse accumulation effect. The specific reasons were analyzed based on theoretical simulation and experimental study. This research work is helpful and of great significance for the construction of high-power LTCL devices.

Background & Aims: Association studies have greatly refined the important role of the major histocompatibility complex (MHC) region in autoimmune hepatitis (AIH). However, the effects of human leucocyte antigen (HLA) polymorphisms on AIH are not well established. The aim of this study is to systematically characterise the association of MHC variants with AIH in our well-defined cohort of patients. Methods: We performed an imputation-based analysis on the extensive association observed within the MHC region using the Han-MHC reference panel, and tested the comprehensive associations of HLA polymorphisms with AIH in 1622 Chinese AIH type 1 patients and 10,466 population controls. Results: A total of 588 HLA variants were significantly associated with AIH, with HLA-B∗35:01 (p = 8.17 × 10−304; odds ratio [OR] = 7.32) contributing the strongest signal. Stepwise conditional analysis revealed additional independent signals at HLA-B∗08:01 (p = 1.35 × 10−33; OR = 4.26) and rs7765379 (p = 5.08 × 10−18; OR = 1.66). A strong link between the lead HLA variant and clinical phenotypes of AIH was observed: patients with HLA-B∗35:01 were less frequently positive for ANA and tended to have higher serum AST and ALT levels at diagnosis, but lower serum IgG levels. Conclusions: Our study reveals three novel and independent variants at HLA-B∗35:01, HLA-B∗08:01, and rs7765379 associated with AIH across the whole MHC region in the Han Chinese population. The findings illustrate the value of the MHC region in AIH and provide a new perspective for the immunogenetics of AIH. Impact and implications: This study revealed three novel and independent variants associated with autoimmune hepatitis across the whole major histocompatibility complex region in the Han Chinese population. These findings are significant in identifying autoantigens, providing insights into the activation of the autoimmune processes, and further advancing our understanding of the immunogenetic basis underlying autoimmune hepatitis.

Abstract Background Colorectal liver metastases attached major intrahepatic vessels has been considered to be a risk factor for survival outcome after liver resection. The present study aimed to clarify the outcomes of R1 surgery (margin 4 cycles, clinical risk score 3–5, RAS mutation, parenchymal R1 and CA199 > 100 IU/ml were identified as independent predictive factors of overall survival (p

Abstract Introduction To evaluate the efficacy and safety of lidocaine patches in Chinese patients with postherpetic neuralgia (PHN). Methods Patients were randomized to receive lidocaine patches or placebo every day for 4 weeks. Efficacy endpoints included the decrease of analogue scale score (VAS) value at week 4, 2 and 1 and the percentage of patients that achieved a 30% decrease of VAS value. Safety analyses were conducted as well. Results Two hundred forty Chinese patients were randomized. At week 1, lidocaine patch-treated patients had a higher clinical response versus placebo, and at week 4, the mean (SD) decreases of VAS value compared to the baseline were 14.01 (14.35) in the treatment group and 9.36 (12.03) in the placebo group (p = 0.0088). Overall, the safety profile in the treatment group was consistent with that observed in the placebo group [adverse event (AE) incidence rate: 33.33% versus 37.29%, p = 0.5857]. Conclusions Lidocaine patches resulted in improved clinical response versus placebo in the treatment of PHN patients and were well tolerated.

Abstract High‐speed Maglev is a cutting‐edge technology brought back into the focus of research by plans of the Chinese government for the development of a new 600 km/h Maglev train. A Chinese‐German cooperation with industrial and academic partners has been established to pursue this ambitious goal and bring together experts from multiple disciplines. This contribution presents the joint work and achievements of CRRC Qingdao Sifang, thyssenkrupp Transrapid, CDFEB, and the ITM of the University of Stuttgart, regarding research and development in the field of high‐speed Maglev systems. Furthermore, an overview is given of the historical development of the Transrapid in Germany, the associated development of dynamical simulation models, and recent developments regarding high‐speed Maglev trains in China.

Background and objective Lung cancer is one of the most common malignant tumors in the world. The accuracy of intraoperative frozen section (FS) in the diagnosis of lung adenocarcinoma infiltration cannot fully meet the clinical needs. The aim of this study is to explore the possibility of improving the diagnostic efficiency of FS in lung adenocarcinoma by using the original multi-spectral intelligent analyzer. Methods Patients with pulmonary nodules who underwent surgery in the Department of Thoracic Surgery, Beijing Friendship Hospital, Capital Medical University from January 2021 to December 2022 were included in the study. The multispectral information of pulmonary nodule tissues and surrounding normal tissues were collected. A neural network model was established and the accuracy of the neural network diagnostic model was verified clinically. Results A total of 223 samples were collected in this study, 156 samples of primary lung adenocarcinoma were finally included, and a total of 1,560 sets of multispectral data were collected. The area under the curve (AUC) of spectral diagnosis in the test set (10% of the first 116 cases) of the neural network model was 0.955 (95%CI: 0.909-1.000, P

Abstract Background Patients with developmental dysplasia of the hip (DDH) have complex proximal femoral deformities, and orthopedic surgery lacks objectivity. Expectations for surgical outcomes are often not achieved, and postoperative problems are common. Using 3D-printed technology in orthopedics offers a novel approach to precise and individualized treatment in modern orthopedics. The aim of this study was to investigate the value of the application of 3D-printed osteotomy guide plates in femoral osteotomy. The clinical indices of femoral osteotomy in children with DDH using 3D-printed osteotomy guide plates were compared with those of traditional osteotomy. Methods The clinical data of children with DDH who underwent open reduction and Salter pelvic osteotomy combined with femoral osteotomy from September 2010 to September 2020 were retrospectively collected and analyzed. Based on the inclusion and exclusion criteria, a total of 36 patients were included in the study: 16 in the guide plate group and 20 in the conventional group. Operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss were analyzed and compared between the two groups. Comparison of treatment-related indicators such as postoperative neck-shaft angle, postoperative anteversion angle, hospitalization time, and hospitalization expenses is made between the two groups. The two groups of patients were evaluated at the last follow-up using the McKay clinical evaluation criteria. Results Between the two groups, there were significant differences in operation time (total), operation time (femoral side), X-ray fluoroscopy times (total), X-ray fluoroscopy times (femoral side) and intraoperative blood loss (P 0.05). The MacKay clinical evaluation did not significantly differ at the most recent follow-up (P > 0.05). Conclusions Children with DDH undergoing proximal femoral osteotomy using 3D-printed osteotomy guide plates benefit from a simpler surgical procedure, shorter operative time, less bleeding and less radiation exposure during surgery. This technique is of great clinical value.

Acute lung injury (ALI) is a progressive inflammatory injury, and mesenchymal stem cells (MSCs) can be used to treat ALI. MSC-conditioned medium (MSC-CM) contains many cytokines, in which keratinocyte growth factor (KGF) is a soluble factor that plays a role in lung development. We aim to explore the protective effects of MSCs secreted KGF on ALI, and investigate the involvement of epithelial sodium channel (ENaC), which are important in alveolar fluid reabsorption. Both lipopolysaccharides (LPS)-induced mouse and alveolar organoid ALI models were established to confirm the potential therapeutic effect of MSCs secreted KGF. Meanwhile, the expression and regulation of ENaC were determined in alveolar type II epithelial (ATII) cells. The results demonstrated that MSC-CM and KGF could alleviate the extent of inflammation-related pulmonary edema in ALI mice, which was abrogated by a KGF neutralizing antibody. In an alveolar organoid ALI model, KGF in MSC-CM could improve the proliferation and decrease the differentiation of ATII cells. At the cellular level, the LPS-inhibited protein expression of ENaC could be reversed by KGF in MSC-CM. In addition, bioinformatics analysis and our experimental data provided the evidence that the NF-κB signaling pathway may be involved in the regulation of ENaC. Our research confirmed that the therapeutic effect of MSC-CM on edematous ALI was closely related to KGF, which may be involved in the proliferation and differentiation of ATII cells, as well as the upregulation of ENaC expression by the inhibition of NF-κB signaling pathway.

Background: Postoperative pulmonary complications (PPCs) are known to adversely affect surgical outcomes and patient prognoses, yet no published study provides a qualitative and quantitative analysis of the latest trends and developments in the field of PPCs. Therefore, we conducted a bibliometric analysis of 20 years of publications related to PPCs. Methods: We examined publications on PPCs published between 2003 and 2022 in the Web of Science Core Collection database to assess trends in the field in four dimensions: trends in publications, major research power, keywords, and co-cited publications. Results: A total of 1881 articles were analyzed using CiteSpace and VOSviewer. Overall, the number of publications on PPCs has increased in the last two decades, with 42.72% of the publications being produced in the last five years. The United States of America had the highest number of articles, accounting for 21.91% of the total. The institution with the highest number of publications was the University of Genoa, which published 54 articles and showed a general lack of inter-institutional collaboration. The most productive author was Paolo Pelosi, with no core group of authors identified in the field of PPCs. The keyword co-occurrence analysis indicated that the focus of research has shifted over the past 20 years in terms of risk factors, type of surgery, and so on, while “enhanced recovery”, “prehabilitation”, “driving pressure” and “sugammadex” have received the most recent attention. In the analysis of co-cited literature, the most recent clusters that received attention were driving pressure, lung cancer patient, enhanced recovery, and neuromuscular blockade. Conclusion: This bibliometric study suggests that pulmonary protective ventilation strategies, neuromuscular blockade reversal, and pulmonary prehabilitation strategy will be the focus of attention in the coming period. More large-scale studies and strengthened institutional collaboration are necessary to generate robust evidence for guiding individualized prevention of PPCs.

ObjectivesTo conduct a systematic review and meta-analysis of prospective cohort studies to investigate the association between total, vegetable, fruit, cereal, soluble and insoluble fiber intake and risk of all causes, cardiovascular disease (CVD), and cancer mortality and quantitatively assess the dose–response relation.MethodsEligible studies were identified by searching PubMed, Embase and Web of science before August 2023. Random effects models were used to calculate summary relative risk (RR) and 95% confidence intervals (CI) and restricted cubic splines to model the linear/non-linear association.ResultsThe summary RR for all-cause, CVD and cancer mortality of dietary fiber was 0.90 (95% CI: 0.86,0.93), 0.87 (0.84,0.91), 0.91 (0.88,0.93), respectively. Significant association was observed for all-cause and CVD mortality with fruit, vegetable cereal and soluble fiber intake and cancer mortality with cereal fiber intake. No significant association was found for insoluble fiber, vegetable or fruit fiber intake and cancer mortality. Dose-response analysis showed a significant non-linear relation of dietary fiber intake with all-cause mortality, and linear relation for others.ConclusionsHigher dietary fiber including different type and food sources of fiber intake were associated with lower risk of mortality. Our findings provide more comprehensive evidence on dietary fiber intake with mortality.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier: CRD42022338837.

Highlights 1. We used exome sequencing to detect and report the genetic changes in a case of extramedullary gastric primary myeloid sarcom with monocytic differentiationa. 2. Immunophenotypic alteration of tumor cells occurred after chemotherapy, suggesting that chemotherapy drugs induced tumor differentiation.

Abstract Esophageal cancer is a familiar malignancy with high incidence and mortality, and the overall prognosis is poor. The numbers of cases of and deaths from esophageal cancer have risen rapidly in recent decades. It is one of the most malignant cancers, with more than 0.6 million new cases and 0.54 million deaths worldwide in 2020. Here, we present the global epidemiology of esophageal cancer in 2020 and projections to 2030 and 2040 at different geographical levels of continents, regions and countries, and analyze them by gender, race, geographic region and human development index. We summarize the prospects for the esophageal cancer burden and risk factors in different areas, which will be useful for global esophageal cancer clinical therapy and cancer control planning.

Lifeways of worldwide people have changed dramatically amid the coronavirus disease 2019 (COVID-19) pandemic, and public health is at stake currently. In the early stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, fibrinolytic system is mostly inhibited, which is responsible for the development of hypofibrinolysis, promoting disseminated intravascular coagulation, hyaline membrane formation, and pulmonary edema. Whereas the common feature and risk factor at advanced stage is a large amount of fibrin degradation products, including D-dimer, the characteristic of hyperfibrinolysis. Plasmin can cleave both SARS-CoV-2 spike protein and γ subunit of epithelial sodium channel (ENaC), a critical element to edematous fluid clearance. In this review, we aim to sort out the role of fibrinolytic system in the pathogenesis of COVID-19, as well as provide the possible guidance in current treating methods. In addition, the abnormal regulation of ENaC in the occurrence of SARS-CoV-2 mediated hypofibrinolysis and hyperfibrinolysis are summarized, with the view of proposing an innovative view of epithelial ion transport in preventing the dysfunction of fibrinolytic system during the progress of COVID-19.

Abstract Background The shortening length of the lower extremity after the proximal femoral osteotomy is an important issue to be considered in preoperative planning of developmental dysplasia of the hip (DDH) in children. There is still a lack of research on shortening the length of the lower extremities in different proximal femoral osteotomy varus styles. We aimed to verify the relationship between the shortening length after “point-to-face” and “face-to-face” varus osteotomy and proposed a formula for calculating the difference in shortening length and verified its feasibility. Methods Fifty-five children with unilateral DDH were enrolled. The preoperative hip CT data were imported into mimics 21, 3-Matic 10 (Materialise, Leuven, Belgium) for femoral reconstruction and simulated osteotomy, and the difference (t) was calculated by directly measuring the length of the proximal femur after osteotomy. d* sinθ was measured in a three-dimensional environment to calculate the difference in femoral shortening length between the two osteotomy methods (t'). Results The results of the direct measurement method and the formula measurement method are shown in the table; the differences in the results of the femoral shortening length difference were not statistically significant (P > 0.05). The limits of agreement (95%) of the difference values using Bland–Altman analysis were between − 0.50 and 0.46 mm, with a mean of − 0.02 mm, indicating a high agreement between the two methods. r = 0.99 (P

Abstract Steroid induced osteonecrosis of the femoral head (ONFH) frequently leads to femoral head collapse and subsequent hip arthritis. This study aimed to investigate the potential therapeutic mechanism of miR‐27a on steroid-induced ONFH. Levels of IL-6, TNF-α, miR-27a, Runx2, PPAR-γ and ApoA5 were first examined in bone marrow tissues from steroid-induced ONFH and controls. Subsequently, we overexpressed or knocked down miR-27a in bone marrow mesenchymal stem cells (BMSCs) and detected cell proliferation, osteogenic differentiation, adipogenic differentiation. In addition, miR-27a mimics and BMSCs were injected into the established steroid-induced ONFH rats, and the osteoprotective effects of both were evaluated. Dual luciferase reporter was used to test the targeting effect of miR-27a-3p and PPARG. miR-27a and Runx2 were lowly expressed in steroid-induced ONFH, PPAR-γ and ApoA5 were highly expressed. Overexpression of miR-27a in BMSCs promoted cell proliferation and osteogenic differentiation, inhibited adipogenic differentiation. Furthermore, increasing miR-27a and BMSCs obviously reduced bone loss in steroid induced ONFH rats. The expressions of Runx2 in BMSCs and steroid-induced ONFH rats was significantly up‐regulated, while IL-6, TNF-α, PPAR-γ and ApoA5 were down‐regulated with miR-27a overexpression. Additionally, PPARG was the target of miR-27a-3p. The results of the present study reveal a role for miR-27a in promoting osteogenesis and may have a synergistic effect with BMSCs.

The structure of subpellicular microtubules (SPMTs) nucleated from the apical polar ring (APR) is essential for Plasmodium parasite morphogenesis, gliding motility, and invasion. Here, Qian et al. characterize the function of APR2 protein in P. yoelii ookinetes. Using co-localization analysis, proximity labeling, CoIP, expansion microscopy and FRAP, they show that APR2 binds to SMPTs and has a fixed position in APR. Deletion mutants fail to traverse the mosquito midgut as they fail to anchor SPMTs on APR, which affects invasive morphology and gliding motility.

Context Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases.Objective To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases.Materials and methods Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01–1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248–992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice.Results Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p

Abstract Background To assess the effectiveness and safety of laryngeal mask anesthesia (LMA) in thoracoscopic pulmonary wedge resection based on patient‐reported outcomes (PROs). Methods This randomized controlled trial included 107 patients who underwent thoracoscopic pulmonary wedge resection between June 2017 and December 2021 for pulmonary nodule or pulmonary bullae. In one group, LMA was applied for general anesthesia, and in the other group, endotracheal intubation (ETT) was used. Results A total of 107 patients were included in the study. The symptom assessment based on PROs showed that the incidence of pharyngodynia, trachyphonia, and cough were lower in the LMA group, while the postoperative gastrointestinal reaction did not significantly differ between the two groups. The pain score and global satisfaction score were significantly better in the LMA group. The satisfaction degree of anesthesia and the surgical field did not significantly differ between the two groups. The anesthesia recovery time, indwelling days of chest catheter, and postoperative hospital stay of the LMA group were all shorter, while the operation time, intraoperative blood loss and lowest intraoperative oxygen saturation did not significantly differ between the two groups. The highest intraoperative partial pressure of CO2 was significantly higher in the LMA group. The artery blood gas analysis after the operation did not significantly differ between the two groups. Conclusion Compared with ETT, the application of LMA may demonstrate promising advantages in airway management for thoracoscopic pulmonary wedge resection. Registration No. of clinical trial (ChiCTR2000034905).

Abstract Background The incidence and mortality of aortic dissection (AD) are increasing. In pathological studies, macrophages, T lymphocytes and dendritic cells were found in the tunica media of the aorta. Acetaldehyde dehydrogenase 2 (ALDH2) gene polymorphisms are associated with a high incidence of hypertension in Asian populations. However, there is no clear evidence of the relationship between ALDH2 and aortic dissection in Asians. The aim of this study was to investigate the incidence of aortic dissection in different ALDH2 genotypes and explore changes in the vasculature. Materials and methods Three-week-old male mice were administered freshly prepared β-aminopropionitrile solution dissolved in drinking water (1 g/kg/d) for 28 days to induce TAD. An animal ultrasound imaging system was used to observe the formation of arterial dissection and changes in cardiac function. Subsequently, mice were euthanized by cervical dislocation. The aortas were fixed for HE staining and EVG staining to observe aortic elastic fiber tears and pseudoluma formation under a microscope. Results Knockout of ALDH2 mitigated β-aminopropionitrile-induced TAD formation in animal studies. Ultrasound results showed that ALDH2 knockout reduced the degree of ascending aortic widening and the incidence of aortic dissection rupture. Pathological sections of multiple aortic segments showed that the protective effect of ALDH2 knockout was observed in not only the ascending aorta but also the aortic arch and descending aorta. The expression levels of genes related to NK CD56bright cells, Th17 cells, T cells and T helper cells were decreased in ALDH2 knockout mice treated with β-aminopropionitrile for 28 days. Conclusion ALDH2 knockout protects against aortic dissection by altering the inflammatory response and immune response and protecting elastic fibers.

Abstract With the railway advancement of speed and load capacity, new high‐power diesel locomotives occupy a prominent position. Due to the susceptibility of onboard signal equipment comprised of microelectronic devices, the diesel locomotive's traction motor (TM) may produce serious disturbance to cab signalling, possibly distorting the signal pattern via receiving coils, even resulting in mutation and decoding error of cab signals. However, the existing research studies pay little attention to this electromagnetic interference problem. This paper studies the radiated alternating magnetic field of the TM and interference coupling path to onboard equipment. It first analyses the cab signalling working principle and clarifies the interference mechanism, focussing on the quantitative analysis of the radiated magnetic field and interference electromotive force. Then, based on the ANSYS platform, the finite element method is used to complete modelling, simulation, and verification. Finally, combined with the railway field data, a typical interference case is analysed, verifying that the distorted signal pulses under the radiated magnetic field are the primary cause of decoding failures. This research establishes the quantitative relationship between the traction radiation intensity and the interference amplitude on signals, helping explore the countermeasures, improve the cab signal decoding accuracy, and ensure transportation efficiency.

Abstract Background With the development of imaging, the etiology of ocular lesions caused by lung cancer was not found only intraocular. Neuro‐ophthalmological imaging has been found to be useful for the diagnosis of meningeal carcinomatosis, although few studies have previously been published. Our study used magnetic resonance imaging (MRI) to determine if there was a the relationship between ocular symptoms and lung cancer metastasis. Methods We carried out a retrospective analysis which included patients with ocular lesions and lung cancer on which orbit MRI was performed together with ocular examination during January 2014 to January 2022. Here, we describe the characteristics of intraocular metastasis and optic nerve sheath lesions. Results A total of 21 lung cancer patients had ocular lesions, of which eight cases had choroidal metastasis; a further eight patients had optic nerve sheath lesions. There was one case (12.5%) of choroidal metastasis with brain or meningeal metastasis, and eight cases (100%) with optic nerve sheath lesions with brain or meningeal metastasis. A total of 75.0% patients with choroidal metastasis did not have any history of known lung cancer, and 25.0% of optic nerve sheath lesions in patients were found before a meningeal metastasis diagnosis. The features of optic nerve sheath lesions included thickening and strengthening of the long segment of the orbital optic nerve sheath with a clear boundary. Conclusions The pathway of choroidal and optic nerve sheath lesions was different. Optic nerve sheath lesions were associated with brain and meningeal metastasis. When lung cancer‐induced meningeal metastasis is suspected, orbital MRI is recommended to assist in the diagnosis.

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern, whereas the effects of cellular microenvironment in the pathogenesis of SARS-CoV-2 are poorly understood. The detailed message of intracellular/lysosome pH was rarely concerned in SARS-CoV-2 infection, which was crucial for the cleavage of SARS-CoV-2 spike (S) protein. Calprotectin, an endogenous danger signal to activate inflammatory response, was vital for the proceeding of COVID-19. We found that the expressions of both vacuolar-ATPase (V-ATPase) and calprotectin (S100A8/S100A9) increased in SARS-CoV-2 infection, by analyzing single-cell RNA sequencing (bronchoalveolar lavage fluid), bulk-RNA sequencing (A549, lung tissue, NHBE), and proteomics (lung tissue), respectively. Furtherly, our wet experiments of flow cytometry and fluorescent assay identified that the intracellular and lysosome pH value was decreased after SARS-CoV-2 S plasmid transfection in A549 cells. Meanwhile, the enhancement of V-ATPase and calprotectin was verified by our real-time polymerase chain reaction and western blot experiment. Collectively, these data suggested that S protein increased V-ATPase in SARS-CoV-2 infection, which provided a microenvironment easier for the cleavage of S protein, and inflammatory cells were apt to be activated by the enhancement of calprotectin in respiratory epithelium. The comprehensive information on profiles of V-ATPase and calprotectin will make clearer about the involvement of cellular microenvironment in the pathogenesis of SARS-CoV-2, and provide a promising approach to combat COVID-19.

BackgroundSmoking remains a major public health problem, and it is important to provide a variety of efficacious and appealing options to encourage smokers to quit smoking. Scheduled smoking is a method of gradual reduction, preparing smokers to quit by systematically reducing cigarette consumption according to a predetermined schedule that increases the time between cigarette consumption. Gradual reduction may be preferred to abrupt quitting, but the efficacy of this cessation approach is unclear. ObjectiveThis study aims, first, to evaluate the overall effectiveness of scheduled smoking alone, or in combination with precessation nicotine replacement therapy (NRT), versus standard NRT starting on the quit date with no prior smoking reduction and, second, to evaluate the impact of schedule compliance on the effectiveness of the intervention. MethodsA total of 916 participants recruited from the Houston metropolitan area were randomly assigned to 1 of the following 3 groups: scheduled smoking plus a precessation nicotine patch (n=306, 33.4%), scheduled smoking only with no precessation patch (n=309, 33.7%), and enhanced usual care (n=301, 32.9%) control. The primary abstinence outcomes were carbon monoxide–verified, self-reported, 7-day point prevalence abstinence at 2 and 4 weeks after the quit date. Unadjusted and adjusted logistic regression analyses were performed to evaluate the intervention effect. Scheduled smoking was implemented using a handheld device for 3 weeks before quitting. This trial was not registered because data collection began before July 1, 2005. ResultsResults for the first aim showed no overall differences in abstinence among the 3 groups in both the unadjusted and adjusted models. However, the results for the second aim showed a clear effect on abstinence by schedule compliance at 2 and 4 weeks and 6 months after quitting (odds ratio [OR] 2.01, 95% CI 1.31-3.07), 4 weeks (OR 1.58, 95% CI 1.05-2.38), and 6 months (OR 1.68, 95% CI 1.04-2.64), with the differences at 2 and 4 weeks after quitting being the most robust. We also found that scheduled smoking was related to a reduction in nicotine withdrawal, negative affect, and craving when compared with the controls. ConclusionsScheduled smoking, when combined with precessation use of NRT, can result in significantly higher abstinence rates than usual care (abrupt quitting with NRT), particularly in the early postquit phase (2 and 4 weeks after cessation) when smokers are compliant with the procedure. Scheduled smoking also produced a better overall quitting experience by reducing symptoms of nicotine withdrawal and craving, in comparison with usual care, which could encourage future quit attempts. Studies in this area should focus on the use of counseling or other methods to improve adherence.

Large-scale aquaculture pen is one of the essential modes of offshore aquaculture being explored in recent years. In contrast to cage farming, the advantages are more significant as the larger cultural space for fish swimming, the closer-to-nature environment, and the improved ecological quality of fish. As a novel offshore aquaculture structure, fully-enclosed pile-net aquaculture pens (FPAPs) are generally deployed in exposed oceans, where severe waves and currents are of great dominance. The hydrodynamic characteristics of FPAPs in offshore areas deserve further investigation. In this paper, the numerical model of a typical FPAP in waves is proposed based on the finite element method (FEM), then wave loads on and induced motion responses of the FPAP are analyzed. The results show that the maximum loads on the structure and the maximum displacement of piles are closely proportional to the wave height. Secondly, the maximum stress of nets decreases as the embedded depth increases, while the deformation of nets tends to rise with the increase of pile spacing. At last, several structural optimal patterns are given to improve the safety of pen facilities. This work has laid a solid scientific foundation for designs and optimizations of FPAPs in the future.

Power system operation mode calculation (OMC) is the basis for unit commitment, scheduling arrangement, and stability analyses. In dispatch centers at all levels, OMC is usually realized by manually adjusting the parameters of power system components. In a new-type power system scenario, a large number of new energy sources lead to a significant increase in the complexity and uncertainty of a system structure, thus further increasing the workload and difficulty of manual adjustment. Therefore, improving efficiency and quality is of particular importance for power system OMC. This paper first considers generator power adjustment and line switching, and it then models the power flow adjustment process in OMC as a Markov decision process. Afterward, an improved deep Q-network (improved DQN) method is proposed for OMC. A state space, action space, and reward function that conform to the rules of the power system are designed. In addition, the action mapping strategy for generator power adjustment is improved to reduce the number of action adjustments and to speed up the network training process. Finally, 14 load levels under normal and N-1 fault conditions are designed. The experimental results on an IEEE-118 bus system show that the proposed method can effectively generate the operation mode under a given load level, and that it has good robustness.