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Abstract Background Hand, foot and mouth disease (HFMD) is a common infectious disease caused by viral infection by a variety of enteroviruses, with coxsackievirus A 10 (CA10) having become more prevalent in recent years. Methods In this study, models of CA10 infection were established in 7‐day‐old Institute of Cancer Research (ICR) mice by intraperitoneal injection to analyze the pathogenicity of the virus. RNA sequencing analysis was used to screen the differentially expressed genes (DEGs) after CA10 infection. Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections were also compared with CA10. Results After CA10 virus infection, the mice showed paralysis of the hind limbs at 3 days post infection and weight loss at 5 days post infection. We observed viral replication in various tissues and severe inflammatory cell infiltration in skeletal muscle. The RNA‐sequencing analysis showed that the DEGs in blood, muscle, thymus and spleen showed heterogeneity after CA10 infection and the most up‐regulated DEGs in muscle were enriched in immune‐related pathways. Compared with CA16 and EV71 infection, CA10 may have an inhibitory effect on T helper (Th) cell differentiation and cell growth. Additionally, the common DEGs in the three viruses were most enriched in the immune system response, including the Toll‐like receptor pathway and the nucleotide‐binding and oligomerization domain (NOD)‐like pathway. Conclusions Our findings revealed a group of genes that coordinate in response to CA10 infection, which increases our understanding of the pathological mechanism of HFMD.

Abstract Image denoising aims to remove noise from images and improve the quality of images. However, most image denoising methods heavily rely on pairwise training strategies and strict prior knowledge about image structure or noise distribution. While these methods exhibit significant results when handling known types of noise, their generalization performance diminishes when confronted with images containing unknown noise distributions. To address this issue, a two‐stage approach is introduced for enhancing the generalizability of image denoising. The proposed method does not rely on a large amount of paired data or prior knowledge of the noise type and level. Instead, it constructs a denoising pipeline with improved generalizability through an MLP‐based denoiser and generative diffusion prior. Specifically, in the first stage, an initial denoised image is predicted with a structure resembling that of the underlying clean image by introducing an MLP‐based U‐shaped denoising network aided by an implicit structural prior. In the second stage, the generalizability and quality of the denoiser are further enhanced by conditioning the result obtained from the previous stage on the pretrained denoising diffusion null‐space model. Extensive experimentation on multiple datasets demonstrates that this method exhibits better denoising performance and generalizability than other image denoising methods.

Abstract Background Although research has explored the association between atherogenic index of plasma (AIP) and prediabetes and diabetes, there is still not sufficient available evidence the role of physical activity (PA) in this relationship. Our purpose is to examine the complex connections between AIP, PA, and prediabetes and diabetes in a young and middle‐aged population. Methods This study included 2220 individuals from the general population, aged 20–60 years. AIP was calculated from the logarithm of the triglyceride (TG) to high‐density lipoprotein cholesterol (HDL‐C) ratio. PA was assessed depending to the American Heart Association (AHA) criteria and categorized into medium‐high and low PA levels. We used binary logistic regression to explore associations and subsequently performed sensitivity and subgroup analyses. Results The 2220 participants had a mean age of 38 years, with a mean AIP of −0.1185, and a prediabetes and diabetes prevalence of 7.2%. After adjusting for auxiliary variables, AIP was positively correlated with prediabetes and diabetes (odds ratio [OR]: 3.447, 95% confidence interval [CI]: 1.829–6.497). In the low PA population, the prevalence of prediabetes and diabetes raised significantly with higher AIP (OR: 3.678, 95% CI: 1.819–7.434). This association was not meaningful in the medium to high PA population (OR: 1.925, 95% CI: 0.411–9.007). Joint and sensitivity analyze results also showed agreement. Restricted cubic spline identified a linear relationship between AIP and the prevalence of prediabetes and diabetes. Notably, the prevalence significantly increases when AIP values exceed −0.16 (p for linearity

ABSTRACT Objective This study aimed to analyze the features of resting‐state functional magnetic resonance imaging (rs‐fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. Methods A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low‐frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed‐based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. Results Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed‐based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. Conclusion The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

ABSTRACT Purpose To explore the diagnostic value of serum apolipoprotein B100 (Apo B100) combined with hippocampal volume in Alzheimer's disease (AD). Methods A total of 59 AD patients and 59 healthy subjects were selected. The Mini‐Mental State Examination (MMSE) was used for neuropsychological assessment. Blood glucose and serum lipid levels were detected by biochemical analyzer. Polymerase chain reaction (PCR) was used to detect apolipoprotein E (Apo E) ε3/ε4 genotypes in the plasma. Hippocampal volume was calculated using Slicer software. Independent‐sample t test or Mann–Whitney U test were used to compare the levels of various indicators between the two groups. Spearman's correlation analysis was used to analyze the correlation between each level. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to compare the diagnostic efficacy of individual and combined detection of serum Apo B100 levels and hippocampal volume in AD. Results Compared with the healthy control group, the levels of serum total cholesterol (TC), low‐density lipoprotein (LDL), Apo B100, and plasma Apo E ε3/ε4 were higher in the AD group, and serum high‐density lipoprotein (HDL) level was lower in the AD group (both p

Abstract Bacillus subtilis is an industrially important microorganism that is often used as a microbial cell factory for the production of recombinant proteins due to its food safety, rapid growth, and powerful secretory capacity. However, the lack of data on functional genes related to recombinant protein production has hindered the further development of B. subtilis cell factories. Here, a strategy combining genome‐wide CRISPRi screening and targeted CRISPRa activation to enhance recombinant protein expression is proposed. First, a CRISPRi library covering a total of 4225 coding genes (99.7%) in the B. subtilis genome and built the corresponding high‐throughput screening methods is constructed. Twelve key genes for recombinant protein expression are identified, including targets without relevant functional annotations. Meanwhile, the transcription of recombinant protein genes by CRISPRa is up‐regulated. These screened or selected genes can be easily applied to metabolic engineering by constructing sgRNA arrays. The relationship between differential pathways and recombinant protein expression in engineered strains by transcriptome analysis is also revealed. High‐density fermentation and generalisability validation results prove the reliability of the strategy. This method can be extended to other industrial hosts to support functional gene annotation and the design of novel cell factories.

Abstract Objective This study aimed to investigate the expressions of glycemic parameters, lipid profile, and thyroid hormone in type 2 diabetes mellitus (T2DM) patients and their correlation. Methods Eighty‐four patients with T2DM in our hospital were included as the observation group. The T2DM patients were divided into mild group, moderate group, and severe group according to the fasting plasma glucose (FPG) level. Another 84 healthy subjects in the same period of health examination in our hospital were included as the control group. The levels of glycemic parameters, (HbA1c and FPG), lipid profile (TC, TG, LDL‐C, and HDL‐C) and thyroid hormone (FT3, TSH, and FT4) were measured by automatic biochemical analyzer. The correlation between glycemic parameters, lipid profile, and thyroid hormone was analyzed by Pearson correlation analysis. Results The FPG, TC, TG, LDL‐C, HbA1c, and TSH levels were significantly elevated, while the HDL‐C and FT3 levels were significantly declined in the observation group versus to control group (p

Abstract Introduction This study aimed to validate the effectiveness, safety and feasibility of water‐filtered infrared A radiation (WIRA) whole‐body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real‐world clinical application prospects. Methods This open‐label single‐arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole‐body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. Results Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow‐up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune‐related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune‐activated cells. Conclusions HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

ABSTRACT Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).

Abstract Objective Unresectable colorectal cancer liver metastasis (CRLM) remains a challenging obstacle that often prevents curative treatment. In this study, we retrospectively analyzed the efficacy and safety of high‐intensity focused ultrasound (HIFU) as a local adjuvant therapy for systemic chemotherapy for patients with unresectable CRLM. HIFU is a noninvasive method previously demonstrated as efficacious for various solid malignancies. Methods Propensity score matching was used for the combination therapy group (HIFU group, n = 59) and the observation group receiving systemic therapy only (No‐HIFU group, n = 59). In addition, the survival benefit, adverse effects, and factors affecting prognosis following HIFU were evaluated. Results The disease control rate was 77.9% and 62.7%, and the objective remission rate was 18.9% and 6.8% in the HIFU and non‐HIFU groups, respectively. The survival analysis showed that median progression‐free survival (mPFS) was 12.0 months and 11.0 months for the HIFU and non‐HIFU groups, respectively (p = 0.002). The univariate and multivariate analysis showed that pre‐treatment colorectal cancer liver metastasis lesion size was significantly associated with mPFS. In addition, patients that received a combination treatment for CRLM lesions

Abstract Aim To investigate the male nurses' engagement in nursing work and the influencing factors. Design A cross‐sectional study. Methods A cross‐sectional survey was conducted in 13 hospitals in China to collect data from 328 male nurses from August to October 2021. A structural equation model design was tested with validated measurement instruments. Results The work engagement of male nurses in China was at a medium level. There was a high correlation of the male nurses' work engagement with career identity (r = 0.764, p

Abstract Dysregulated circular RNAs (circRNAs) contribute to tumourigenesis and cancer progression. However, the expression patterns and biological functions of circRNAs in colorectal cancer (CRC) remain elusive. Here, RNA sequencing and bioinformatics analyses are applied to screen for aberrantly expressed circRNAs. The expression of circFBXW4 in CRC tissues and cell lines is determined by quantitative real‐time PCR. A series of in vitro and in vivo biological function assays are implemented to assess the functions of circFBXW4. The regulatory mechanisms linking circFBXW4, miR‐338‐5p, and SLC5A7 are explored by western blotting, dual luciferase reporter assays, and RNA pull‐down assays. CircFBXW4 is dramatically downregulated in CRC tissues and cell lines. circFBXW4 downregulation is clearly correlated with malignant features and patient overall survival in CRC. Functionally, ectopic expression of circFBXW4 strikingly impairs the proliferation, migration, and invasion capacities of CRC cells in vitro and in vivo, whereas circFBXW4 knockdown has the opposite effects. Mechanistically, circFBXW4 competitively binds to miR‐338‐5p and prevents it from interacting with and repressing its target SLC5A7, thus suppressing the progression of CRC. This study reveals the specific critical role of circFBXW4 in inhibiting CRC progression via the miR‐338‐5p/SLC5A7 axis and provides an additional target for eradicating CRC.

Abstract This study aims to assess clinical outcomes following switching from originator to generic amlodipine. This population‐based, matched, cohort study included users of originator amlodipine using claims data during 2018–2020 from a health system in Tianjin, China, in which usage of generic amlodipine was promoted by a drug procurement policy, the national volume‐based procurement. Non‐switchers refer to those remained on originator after the policy, while pure‐switchers were those who switched to and continued using generic amlodipine, and back‐switchers were those switched to generic amlodipine but then back to the originator. Propensity score matching generates comparable non‐switchers and pure‐switchers pairs, and non‐switchers and back‐switchers pairs. The primary outcome was major adverse cardiovascular events (MACEs), defined as all‐cause mortality, stroke, and myocardial infarction during follow‐up (April 1, 2019 to December 30, 2020). Secondary outcomes included heart failure, atrial fibrillation, and adherence to amlodipine. The hazard ratio (HR) for each clinical outcome was assessed through Cox proportional hazard regression. In total, 5943 non‐switchers, 2949 pure‐switchers, and 3061 back‐switchers were included (mean age: 62.9 years; 55.5% men). For the matched pairs, pure‐switchers (N = 2180) presented no additional risks of clinical outcomes compared to non‐switchers (N = 4360) (e.g., MACEs: 2.86 vs. 2.95 events per 100 person‐years; HR = 0.97 [95%CI: 0.70–1.33]). Back‐switchers (N = 1998) also presented no additional risk compared to non‐switchers (N = 3996) for most outcomes except for stroke (HR = 1.55 [95%CI: 1.03–2.34]). Pure‐switchers and back‐switchers all had better amlodipine adherence than non‐switchers. Generic substitution of amlodipine is not associated with increased risk of cardiovascular events or all‐cause mortality, but improves medicine adherence.

Abstract Background To examine standardized uptake valuemax of the primary lesion (pSUVmax) and tumor markers (TMs) for clinically predicting distant metastasis in novo lung adenocarcinoma. Methods The current retrospective observational study examined individuals diagnosed with de novo lung adenocarcinoma at Shanxi Cancer Hospital between February 2015 and December 2019. Results Totally, 532 de novo lung adenocarcinoma cases were included. They were aged 60.8 ± 9.7 years and comprised 224 women and 268 patients with distant metastasis. The areas under the curves (AUCs) of pSUVmax, lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), cytokeratin‐19 fragment (CYFRA21‐1), carbohydrate antigen 125 (CA125), and Grade of TMs for predicting distant metastasis were 0.742, 0.601, 0.671, 0.700, 0.736, and 0.745, respectively. The combination of pSUVmax, LDH, CEA, CYFRA21‐1, CA125, and grade of TMs in predicting distant metastasis had an AUC value of 0.816 (95%CI: 0.781–0.851), with sensitivity of 89.2%, specificity of 58.7%, positive predictive value of 73.7%, and negative predictive value of 79.7%, respectively. Conclusions pSUVmax combined with serum levels of LDH, CEA, CYFRA21‐1, CA125, and the grade of TMs may have good performance in predicting distant metastasis of de novo lung adenocarcinoma.

Abstract Ginger (Zingiber officinale Roscoe) is an important plant used worldwide for medicine and food. The R2R3‐MYB transcription factor (TF) family has essential roles in plant growth, development, and stresses resistance, and the number of genes in the family varies greatly among different types of plants. However, genome‐wide discovery of ZoMYBs and gene responses to stresses have not been reported in ginger. Therefore, genome‐wide analysis of R2R3‐MYB genes in ginger was conducted in this study. Protein phylogenetic relations and conserved motifs and chromosome localization and duplication, structure, and cis‐regulatory elements were analyzed. In addition, the expression patterns of selected genes were analyzed under two different stresses. A total of 299 candidate ZoMYB genes were discovered in ginger. Based on groupings of R2R3‐MYB genes in the model plant Arabidopsis thaliana (L.) Heynh., ZoMYBs were divided into eight groups. Genes were distributed across 22 chromosomes at uneven densities. In gene duplication analysis, 120 segmental duplications were identified in the ginger genome. Gene expression patterns of 10 ZoMYBs in leaves of ginger under abscisic acid (ABA) and low‐temperature stress treatments were different. The results will help to determine the exact roles of ZoMYBs in anti‐stress responses in ginger.

Abstract Reprogramming metabolic flux is a promising approach for constructing efficient microbial cell factories (MCFs) to produce chemicals. However, how to boost the transmission efficiency of metabolic flux is still challenging in complex metabolic pathways. In this study, metabolic flux is systematically reprogrammed by regulating flux size, flux direction, and flux rate to build an efficient MCF for chondroitin production. The ammoniation pool for UDP‐GalNAc synthesis and the carbonization pool for UDP‐GlcA synthesis are first enlarged to increase flux size for providing enough precursors for chondroitin biosynthesis. Then, the ammoniation pool and the carbonization pool are rematched using molecular valves to shift flux direction from cell growth to chondroitin biosynthesis. Next, the adaptability of polymerization pool with the ammoniation and carbonization pools is fine‐tuned by dynamic and static valve‐based adapters to accelerate flux rate for polymerizing UDP‐GalNAc and UDP‐GlcA to produce chondroitin. Finally, the engineered strain E. coli F51 is able to produce 9.2 g L−1 chondroitin in a 5‐L bioreactor. This strategy shown here provides a systematical approach for regulating metabolic flux in complex metabolic pathways for efficient biosynthesis of chemicals.

Abstract Aims/Introduction Fibrosis is the principle reason for heart failure in diabetes. Regarding the involvement of long non‐coding ribonucleic acid zinc finger E‐box binding homeobox 1 antisense 1 (ZEB1‐AS1) in diabetic myocardial fibrosis, we explored its specific mechanism. Materials and Methods Human cardiac fibroblasts (HCF) were treated with high glucose (HG) and manipulated with plasmid cloning deoxyribonucleic acid 3.1‐ZEB1‐AS1/microribonucleic acid (miR)‐181c‐5p mimic/short hairpin RNA specific to sirtuin 1 (sh‐SIRT1). ZEB1‐AS1, miR‐181c‐5p expression patterns, cell viability, collagen I and III, α‐smooth muscle actin (α‐SMA), fibronectin levels and cell migration were assessed by reverse transcription quantitative polymerase chain reaction, cell counting kit‐8, western blot and scratch tests. Nuclear/cytosol fractionation assay verified ZEB1‐AS1 subcellular localization. The binding sites between ZEB1‐AS1 and miR‐181c‐5p, and between miR‐181c‐5p and SIRT1 were predicted and verified by Starbase and dual‐luciferase assays. The binding of SIRT1 to Yes‐associated protein (YAP) and YAP acetylation levels were detected by co‐immunoprecipitation. Diabetic mouse models were established. SIRT1, collagen I, collagen III, α‐SMA and fibronectin levels, mouse myocardium morphology and collagen deposition were determined by western blot, and hematoxylin–eosin and Masson trichrome staining. Results Zinc finger E‐box binding homeobox 1 antisense 1 was repressed in HG‐induced HCFs. ZEB1‐AS1 overexpression inhibited HG‐induced HCF excessive proliferation, migration and fibrosis, and diminished collagen I, collagen III, α‐SMA and fibronectin protein levels in cells. miR‐181c‐5p had targeted binding sites with ZEB1‐AS1 and SIRT1. SIRT1 silencing/miR‐181c‐5p overexpression abrogated ZEB1‐AS1‐inhibited HG‐induced HCF proliferation, migration and fibrosis. ZEB1‐AS1 suppressed HG‐induced HCF fibrosis through SIRT1‐mediated YAP deacetylation. ZEB1‐AS1 and SIRT1 were repressed in diabetic mice, and miR‐181c‐5p was promoted. ZEB1‐AS1 overexpression improved myocardial fibrosis in diabetic mice, and reduced collagen I, collagen III, α‐SMA and fibronectin protein levels in myocardial tissues. Conclusion Long non‐coding ribonucleic acid ZEB1‐AS1 alleviated myocardial fibrosis through the miR‐181c‐5p–SIRT1–YAP axis in diabetic mice.

Abstract This paper studies the iterative learning control (ILC) for a class of second‐order nonlinear hyperbolic impulsive partial differential systems. Firstly, to follow the discontinuous desired output, a P‐type learning law is adopted, and sufficient conditions for the convergence of the tracking error is established under identified initial state value. The rigorous analysis is also given using the impulsive Gronwall inequality. Secondly, the tracking error of output trajectory is considered in systems with state initial values shifting based on an initial learning algorithm. These results of this paper show that the tracking error on the finite time interval can uniform converge to 0 as the iteration index goes to infinity if impulse number of the systems is only a finite numbers. Finally, two numerical simulation examples are given to verify the effectiveness of the theoretical results.

Abstract Background Evidence has shown that early‐life famine exposure and obesity in adulthood are independently associated with the risk of type 2 diabetes mellitus (T2DM). However, few studies had revealed the combined effect of these risk factors. Methods Two sets of groups from the China Health and Retirement Longitudinal Study (CHARLS) were selected. The fetal‐exposure group born in 1959–1961 from 2011 wave (N = 958) and nonexposure group born in 1963–1965 from 2015 wave (N = 1540) were selected as Comparison 1. The early childhood‐exposure group born in 1955–1957 from 2011 wave (N = 1510) and fetal‐exposure group born in 1959–1961 from 2015 wave (N = 943) were Comparison 2. Logistic regressions were applied to examine the associations of different famine exposure periods and obesity patterns with T2DM risk. Results Compared with nonexposed participants without central overweight/obesity in adulthood, central overweight/obesity in adulthood together with nonexposure (odds ratio [OR]: 1.89, 95% confidence interval [CI]: 1.19–3.00) or fetal‐exposure (OR: 1.99, 95% CI: 1.23–3.23) was associated with higher risks of T2DM. Compared with the early childhood‐exposure group, the fetal‐exposed participants showed higher risks of T2DM (OR: 1.30, 95% CI: 1.02–1.66). The coexistence of fetal famine exposure and central overweight/obesity in adulthood was associated with higher risks of T2DM (OR: 1.82, 95% CI: 1.19–2.79). Consistent associations were observed among males and participants from less severely affected areas. Conclusions In conclusion, central overweight/obesity in adulthood is associated with the increased risk of T2DM, but the effect of early‐life famine exposure is not very clear.

Abstract IGF2BP2 is a new identified N6‐methyladenosine (m6A) reader and associated with poor prognosis in many tumors. However, its role and related mechanism in breast cancer, especially in triple‐negative breast cancer (TNBC), remains unclear. In this study, it is found that IGF2BP2 is highly expressed in TNBC due to the lower methylation level in its promoter region. Functional and mechanical studies displayed that IGF2BP2 could promote TNBC proliferation and the G1/S phase transition of the cell cycle via directly regulating CDK6 in an m6A‐dependent manner. Surprising, the regulation of protein levels of CDK6 by IGF2BP2 is related to the changes in translation rate during translation initiation, rather than mRNA stability. Moreover, EIF4A1 is found to be recruited by IGF2BP2 to promote the translation output of CDK6, providing new evidence for a regulatory role of IGF2BP2 between m6A methylation and translation. Downregulation of IGF2BP2 in TNBC cell could enhance the sensitivity to abemaciclib, a CDK4/6 inhibitor. To sum up, our study revealed IGF2BP2 could facilitate the translation output of CDK6 via recruiting EIF4A1 and also provided a potential therapeutic target for the diagnosis and treatment of TNBC, as well as a new strategy for broadening the drug indications for CDK4/6 inhibitors.

Abstract Objective Polo‐like kinase 1 (PLK1), a serine/threonine‐protein kinase, functions as a potent oncogene in the initiation and progression of tumor. The aim of this study is to assess potential correlations between PLK1 expression and immune infiltration in breast cancer (BRCA) and construct a PLK1‐based immune risk model applicable for prognosis and treatment response prediction in BRCA. Methods We collected data on PLK1 gene expression in BRCA patients from The Cancer Genome Atlas (TCGA) database. Thereafter, we analyzed the associations of PLK1 expression with immune cell infiltration and immunomodulators, and established a prognostic risk model based on seven PLK1‐associated immunomodulator genes and a nomogram for survival prediction. Results BRCA prognosis, clinical stage progression, and tumor classification were all shown to be substantially correlated with PLK1 expression. The PLK1 gene was significantly enriched in T cell and B cell receptors and molecules of the chemokine signaling pathways. Specifically, PLK1 expression was positively correlated with the CD8+ T cell and regulatory T cell (Tregs) activation and negatively correlated with M2 macrophage infiltration. The seven‐genes‐based risk model could serve as an independent prognostic factor of BRCA. The risk model was markedly correlated with the expression of programmed cell death protein 1/programmed cell death ligand 1 (PD‐1/PD‐L1; both p

Abstract Background As one of the most devastating cancers, head and neck squamous cell carcinoma (HNSCC) has a short survival time and poor prognosis. Pescadillo ribosomal biogenesis factor 1 (PES1) plays a critical role in the progression of numerous cancers. However, its role and underlying mechanisms in HNSCC remain unclear. Methods A variety of bioinformatic approaches were used to identify the expressions, prognostic and diagnostic value of PES1 in HNSCC. qRT‐PCR, immunofluorescence (IF) assay, western blotting and immunohistochemical (IHC) were used to evaluate the expression of PES1 in HNSCC cell lines and clinical tissues. PES1 was knocked down in TU177 and FaDu cells which have high PES1 expression. The effects of PES1 on cell proliferation and tumour growth in HNSCC were elevated by colony formation, CCK8 assays and tumorigenicity assay in nude mice. The effects on cisplatin (CDDP) sensitivity upon silencing of PES1 were assessed using a patient‐derived xenograft (PDX) model. Results PES1 expression was an independent prognostic factor for HNSCC and negatively associated with the overall survival rate. Silencing of PES1 reduces HNSCC cell proliferation and tumour growth. Moreover, PES1 inhibition significantly sensitises HNSCC cells to cisplatin. Furthermore, we found a PES1 has a high correlation with c‐Myc and plays an essential role in the tumour immune microenvironment. Conclusion Our findings suggest that PES1 is associated with tumour growth and drug resistance and served as a potential cancer marker for diagnosis and a putative therapeutic target for HNSCC.

Abstract The spike protein of SARS‐CoV‐2 hijacks the host angiotensin converting enzyme 2 (ACE2) to meditate its entry and is the primary target for vaccine development. Nevertheless, SARS‐CoV‐2 keeps evolving and the latest Omicron subvariants BQ.1 and XBB have gained exceptional immune evasion potential through mutations in their spike proteins, leading to sharply reduced efficacy of current spike‐focused vaccines and therapeutics. Compared with the fast‐evolving spike protein, targeting host ACE2 offers an alternative antiviral strategy that is more resistant to viral evolution and can even provide broad prevention against SARS‐CoV and HCoV‐NL63. Here, we use prime editor (PE) to precisely edit ACE2 at structurally selected sites. We demonstrated that residue changes at Q24/D30/K31 and/or K353 of ACE2 could completely ablate the binding of tested viruses while maintaining its physiological role in host angiotensin II conversion. PE‐mediated ACE2 editing at these sites suppressed the entry of pseudotyped SARS‐CoV‐2 major variants of concern and even SARS‐CoV or HCoV‐NL63. Moreover, it significantly inhibited the replication of the Delta variant live virus. Our work investigated the unexplored application potential of prime editing in high‐risk infectious disease control and demonstrated that such gene editing‐based host factor reshaping strategy can provide broad‐spectrum antiviral activity and a high barrier to viral escape or resistance.

Abstract Objective Anxious behaviors often occur in individuals who have experienced early adversity. Anxious behaviors can bring many hazards, such as social withdrawal, eating disorders, negative self‐efficacy, self‐injurious thoughts and behaviors, anxiety disorders, and even depression. Abnormal behavior are is closely related to changes in corresponding circuit functions in the brain. This study investigated the relationship between brain circuits and anxious behaviors in maternal‐deprived rhesus monkey animal model, which mimic early adversity in human. Methods Twenty‐five rhesus monkeys (Macaca mulatta) were grouped by two different rearing conditions: 11 normal control and mother‐reared (MR) monkeys and 14 maternally deprived and peer‐reared (MD) monkeys. After obtaining images of the brain areas with significant differences in maternal separation and normal control macaque function, the relationship between functional junction intensity and stereotypical behaviors was determined by correlation analysis. Results The correlation analysis revealed that stereotypical behaviors were negatively correlated with the coupling between the left lateral amygdala subregion and the left inferior frontal gyrus in both MD and MR macaques. Conclusion This study suggests that early adversity‐induced anxious behaviors are associated with changes in the strength of the amygdala–prefrontal connection. The normalization of the regions involved in the functional connection might reverse the behavioral abnormality. It provides a solid foundation for effective intervention in human early adversity. Significance Statement This study suggests that early adversity‐induced anxious behaviors are associated with changes in the strength of the amygdala–prefrontal connection. The higher the amygdala–prefrontal connection strength, the less stereotyped behaviors exhibited by monkeys experiencing early adversity. Thus, in the future, changing the strength of the amygdala–prefrontal connection may reverse the behavioral abnormalities of individuals who experience early adversity. This study provides a solid foundation for effective intervention in humans' early adversity.

Abstract The aim of this study was to identify miRNAs in plasma exosomes as noninvasive biomarkers for the early diagnosis of lung adenocarcinoma (LUAD). First, exosomal miRNA profiling of three patients with early LUAD and three patients with benign lung disease were screened by next‐generation sequencing (NGS) method. Sequencing results showed that 154 exosomal miRNAs were differentially expressed in the plasma of LUAD patients, among which 68 miRNAs were up‐regulated and 86 miRNAs were down‐regulated. GSE137140 is a GEO database containing serum miRNAs sequencing data from 1566 lung cancer patients and 1774 non‐cancer patients controls. When comparing the sequencing data, it was found that most miRNAs (37/68) up‐regulated in our LUAD group were also significantly up‐regulated in GSE137140, suggesting that circulating miRNAs in lung cancer patients may be enriched in plasma exosomes. In GSE137140, the AUC of the combination of hsa‐miR‐103b, hsa‐miR‐29c‐5p and hsa‐miR‐877‐5p was 0.873, showing great potential as new tumor markers. To our knowledge, these three exosomal miRNAs have not been reported in lung cancer research. Furthermore, bioinformatics tools were used to analyze the target genes of three candidate miRNAs, which were indeed closely related to the occurrence and development of lung cancer. Bioinformatics algorithms deduced a highly conserved sequence in the 3’‐UTR of SFRP4, FOXM1 and TMEM98 that could be bound with miR‐103b/877‐5p/29c‐5p. A luciferase assay indicated that miR‐103b/877‐5p/29c‐5p directly targeted the 3’‐UTR of SFRP4, FOXM1 and TMEM98, respectively. Finally, three candidate miRNAs were validated by qRT‐PCR in 17 early LUAD samples and 17 control plasma samples. Integration of bioinformatics analysis and experimental validation identifies, this study provides novel insights into miRNA‐related networks in LUAD. Hsa‐miR‐103b, hsa‐miR‐29c‐5p, and hsa‐miR‐877‐5p may be used as diagnostic biomarkers for early LUAD.

Abstract Hypocalcemia is a fatal electrolytic disorder defined as corrected serum total calcium levels

Abstract Background Several studies have examined gut microbiota and sarcopenia using 16S ribosomal RNA amplicon sequencing; however, this technique may not be able to identify altered specific species and functional capacities of the microbes. We performed shotgun metagenomic sequencing to compare the gut microbiome composition and function between individuals with and without sarcopenia. Methods Participants were from a community‐based observational study conducted among the residents of rural areas in China. Appendicular skeletal muscle mass was assessed using direct segmental multi‐frequency bioelectrical impedance and grip strength using a Jamar Hydraulic Hand dynamometer. Physical performance was evaluated using the Short Physical Performance Battery, 5‐time chair stand test and gait speed with the 6 m walk test. Sarcopenia and its severity were diagnosed according to the Asian Working Group for Sarcopenia 2019 algorithm. The gut microbiome was profiled by shotgun metagenomic sequencing to determine the microbial composition and function. A gut microbiota‐based model for classification of sarcopenia was constructed using the random forest model, and its performance was assessed using the area under receiver‐operating characteristic curve (AUC). Results The study sample included 1417 participants (women: 58.9%; mean age: 63.3 years; sarcopenia prevalence: 10.0%). β‐diversity indicated by Bray–Curtis distance (genetic level: P = 0.004; taxonomic level of species: P = 0.020), but not α‐diversity indicated by Shannon index (genetic level: P = 0.962; taxonomic level of species: P = 0.922), was significantly associated with prevalent sarcopenia. After adjusting for potential confounders, participants with sarcopenia had higher relative abundance of Desulfovibrio piger (P = 0.003, Q = 0.090), Clostridium symbiosum (P

Abstract Fluctuations in monsoonal climate on orbital‐ to millennial‐timescales have had a major impact on vegetation change in East Asia since the last deglaciation. However, the influence of centennial‐scale oscillations on the spatio‐temporal characteristics of vegetation and climate during the last deglaciation remains controversial. We present a well‐dated, decadal‐resolution pollen record from the sediments of annually laminated Lake Xiaolongwan in Northeast Asia, which reveals major orbital‐/millennial‐scale and minor quasi‐periodic, that is, ∼500‐year (yr) cyclic, vegetation changes from ∼19.96 to ∼10.79 Kyr ago (covering the last deglaciation). The ∼500‐yr cycles are characterized by alternations in broadleaved forest/boreal coniferous forest with tundra steppe representing warm and humid/cold and dry phases of the monsoonal climate. This cyclicity may be related to El Niño‐like/La Niña‐like state and low‐latitude atmosphere‐ocean processes, against the background of the long‐term trend of the deglacial climatic evolution. Our findings demonstrate a close relationship between ecosystem succession and climate change on centennial scale.

Abstract Background Mucosal melanoma has characteristically distinct genetic features and typically poor prognosis. The lack of representative mucosal melanoma models, especially cell lines, has hindered translational research on this melanoma subtype. In this study, we aimed to establish and provide the biological properties, genomic features and the pharmacological profiles of a mucosal melanoma cell line that would contribute to the understanding and treatment optimization of molecularly‐defined mucosal melanoma subtype. Methods The sample was collected from a 67‐year‐old mucosal melanoma patient and processed into pieces for the establishment of cell line and patient‐derived xenograft (PDX) model. The proliferation and tumorigenic property of cancer cells from different passages were evaluated, and whole‐genome sequencing (WGS) was performed on the original tumor, PDX, established cell line, and the matched blood to confirm the establishment and define the genomic features of this cell line. AmpliconArchitect was conducted to depict the architecture of amplified regions detected by WGS. High‐throughput drug screening (HTDS) assay including a total of 103 therapeutic agents was implemented on the established cell line, and selected candidate agents were validated in the corresponding PDX model. Results A mucosal melanoma cell line, MM9H‐1, was established which exhibited robust proliferation and tumorigenicity after more than 100 serial passages. Genomic analysis of MM9H‐1, corresponding PDX, and the original tumor showed genetic fidelity across genomes, and MM9H‐1 was defined as a triple wild‐type (TWT) melanoma subtype lacking well‐characterized “driver mutations”. Instead, the amplification of several oncogenes, telomerase reverse transcriptase (TERT), v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF), melanocyte Inducing transcription factor (MITF) and INO80 complex ATPase subunit (INO80), via large‐scale genomic rearrangement potentially contributed to oncogenesis of MM9H‐1. Moreover, HTDS identified proteasome inhibitors, especially bortezomib, as promising therapeutic candidates for MM9H‐1, which was verified in the corresponding PDX model in vivo. Conclusions We established and characterized a new mucosal melanoma cell line, MM9H‐1, and defined this cell line as a TWT melanoma subtype lacking well‐characterized “driver mutations”. The MM9H‐1 cell line could be adopted as a unique model for the preclinical investigation of mucosal melanoma.

Abstract A secreted 50‐kDa metalloprotease from Serratia marcescens D15 was identified as rice protein hydrolase (SeMPase), which reached the highest proteolytic activity (477.3 U/ml) in basal medium with 1.5% rice protein (RP) at 35°C and 150 rpm for 48 h. SeMPase exhibited a highest catalytic number for RP (275.8 min−1, Kcat), which contained a highly conserved Zn2+‐binding (HEIGH) domain, Met‐turn (SLMSY), and Ca2+ binding domain (GGAGND). RP hydrolysates that prepared by SeMPase showed the highest content of oligopeptides at 72.3%, compared to 64.1% from neutrase, 63.0% from alcalase, 50.2% from trypsin, 47.1% from flavourzyme, and 2.41% from pepsin. Our results showed that cleavage sites of SeMPase exposed in RP are more than those of other proteases because both SeMPase cleavage sites and the amino acid composition of RP are rich in Leu, Val, Phe, Glu, and Ala. SeMPase has significant specificity for the preparation of oligopeptide‐enriched RP hydrolysates, which provides a new and highly valued option for industrial preparation of oligopeptide‐enriched protein hydrolysates.

Background Acute myocardial infarction (AMI) with essential thrombocythemia (ET) or polycythemia vera is rare, and there are scarce real‐world data on its management and impact on in‐hospital outcomes. Methods and Results Dates of current retrospective cohort study were obtained from the US National Inpatient Sample from October 2015 to 2019 for hospitalizations with AMI. The primary outcome was in‐hospital mortality, and the secondary outcome was major adverse cardiac or cerebrovascular events, stroke, and bleeding; major adverse cardiac or cerebrovascular event was defined by a composite of all‐cause mortality, stroke, and cardiac complications. Of the 2 871 934 weighted AMI hospitalizations, 0.27% were with ET and 0.1% were with polycythemia vera. Before propensity matching, AMI hospitalization with ET was associated with increased risk of in‐hospital mortality (7.1% versus 5.7%; odds ratio [OR], 1.14 [95% CI, 1.04–1.24]), major adverse cardiac or cerebrovascular events (12.6% versus 9%; OR, 1.36 [95% CI, 1.26–1.45]), bleeding (12.7% versus 5.8%; OR, 2.28 [95% CI, 2.13–2.44]), and stroke (3.1% versus 1.8%; OR, 1.66 [95% CI, 1.46–1.89]). Polycythemia vera was associated with an increased risk of in‐hospital mortality (7.8% versus 5.7%; OR, 1.21 [95% CI, 1.04–1.39]) and major adverse cardiac or cerebrovascular events (12.0% versus 9%; OR, 1.18 [95% CI, 1.05–1.33]). After propensity matching, ET was associated with increased risk of bleeding (12.6% versus 6.1%; OR, 2.22 [95% CI, 1.70–2.90]), and AMI with polycythemia vera was not associated with worse in‐hospital outcomes. Conclusions AMI hospitalization with ET is associated with high bleeding risk before and after propensity score matching, particularly for hospitalizations treated with percutaneous coronary intervention. The management of AMI requires a multidisciplinary and patient‐centered approach to ensure safety and improve outcomes.

Abstract G protein‐coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence‐specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor‐xenografted mouse models and patient‐derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin‐angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.

Abstract The uncertainty of both the generation side and the user side brings certain impacts on the source‐load coordinated operation of integrated energy system (IES). At first, the source‐load characteristics of the IES with large‐scale distributed energy is analyzed. Secondly, considering lower operating cost and higher renewable energy consumption rate, a bilevel optimization model of the source‐load coordination based on the IES operation structure is established, which considers the uncertainty of both the generation side, such as wind and photovoltaic (PV) power output, and the load side. The robust optimization theory and stochastic chance‐constrained programming theory are introduced to establish the upper layer and the lower layer models of the IES. Besides, the firefly algorithm is used to design the solution process of the bilevel optimization model. The results show that the uncertainty of the wind power, PV power, and the load are positively correlated with the comprehensive operation cost. Also, based on the full consideration of the bilevel uncertainties, the system operation cost is significantly reduced. Meanwhile, the improvement of the confidence level of the objective function and constraint conditions will enhance the optimistic value of the comprehensive operation cost of the system, which means gaining higher reliability by sacrificing partial system benefits. Overall, the bilevel optimization model considering the source‐load uncertainty can both improve the renewable energy consumption rate and reduce the comprehensive operation cost of the IES system.

Abstract Background Long non‐coding RNA (lncRNA) HULC (highly upregulated in liver cancer) is considered as an oncogenic factor for various malignant tumors. This study aimed to reveal the role of lncRNA HULC in the malignant behavior of glioblastoma (GBM) by exploring its effects on the epithelial–mesenchymal transition (EMT) and vasculogenic mimicry (VM) of human GBM. Materials and Methods The contents of VM in 27 GBM samples were assessed by immunohistochemistry‐histology and their association with progress‐free survival (PFS) was analyzed. Human GBM SHG44 and U87 cells were manipulated to establish stable lncRNA HULC overexpressing and silencing cells by lentivirus‐based technology. The effects of altered lncRNA HULC on vasculogenic tubular formation, invasion, and EMT process in GBM cells were tested in vitro and the growth of implanted GBM tumors and their EMT process were examined in vivo. Results The numbers of VM were positively associated with disease progression, but negatively with PFS periods of GBM patients. Compared with the control vec cells, lncRNA HULC overexpression significantly increased the tubular formation, invasion, and EMT process of both SHG44 and U87 cells, accompanied by promoting the growth of implanted GBM tumors and EMT process in mice. LncRNA HULC silencing had opposite effects on the tubular formation, invasion, and EMT process as well as tumor growth of GBM cells. Conclusion LncRNA HULC stimulates the EMT process and VM in human GBM, and may be a therapeutic target for intervention of GBM.

Abstract Cognitive decline is amongst one of the most commonly reported complaints during normal aging. Despite evidence that age and cognition are linked with similar neural correlates, no previous studies have directly ascertained how these two constructs overlap in the brain in terms of neuroimaging‐based prediction. Based on a long lifespan healthy cohort (CamCAN, aged 19–89 years, n = 567), it is shown that both cognitive function (domains spanning executive function, emotion processing, motor function, and memory) and human age can be reliably predicted from unique patterns of functional connectivity, with models generalizable in two external datasets (n = 533 and n = 453). Results show that cognitive decline and normal aging both manifest decrease within‐network connections (especially default mode and ventral attention networks) and increase between‐network connections (somatomotor network). Whereas dorsal attention network is an exception, which is highly predictive on cognitive ability but is weakly correlated with aging. Further, the positively weighted connections in predicting fluid intelligence significantly mediate its association with age. Together, these findings offer insights into why normal aging is often associated with cognitive decline in terms of brain network organization, indicating a process of neural dedifferentiation and compensational theory.

Abstract Transition metal dichalcogenides (TMDs) possess intrinsic spin–orbit interaction (SOI) with high potential to be exploited for various quantum phenomena. SOI allows the manipulation of spin degree of freedom by controlling the carrier's orbital motion via mechanical strain. Here, strain modulated spin dynamics in bilayer MoS2 field‐effect transistors (FETs) fabricated on crested substrates are demonstrated. Weak antilocalization (WAL) is observed at moderate carrier concentrations, indicating additional spin relaxation path caused by strain fields arising from substrate crests. The spin lifetime is found to be inversely proportional to the momentum relaxation time, which follows the Dyakonov–Perel spin relaxation mechanism. Moreover, the spin–orbit splitting is obtained as 37.5 ± 1.4 meV, an order of magnitude larger than the theoretical prediction for monolayer MoS2, suggesting the strain enhanced spin‐lattice coupling. The work demonstrates strain engineering as a promising approach to manipulate spin degree of freedom toward new functional quantum devices.

Abstract Organic phosphorescence materials have received wide attention in bioimaging for bio‐low toxicity and large Stokes. Herein, a design strategy to achieve near‐infrared (NIR) excitation and emission of organic room‐temperature phosphorescence through two‐stage confinement supramolecular assembly is presented. Via supramolecular macrocyclic confinement, the host–guest complexes exhibit phosphorescence with two‐photon absorption (excitation wavelength up to 890 nm) and NIR emission (emission wavelength up to 800 nm) in aqueous solution, and further nano‐confinement assembly significantly strengthens phosphorescence. Moreover, the nano‐assemblies possess color‐tunable luminescence spanning from the visible to NIR regions under different excitation wavelengths. Intriguingly, the prepared water‐soluble assemblies maintain two‐photon absorption and multicolor luminescence in cells or vivo.

Although the structure and composition of collagen have been studied by polarized light microscopy since the early 19th century, many studies and reviews have paid little or no attention to the morphological problems of histopathological diagnosis. The morphology of collagen fibers is critical in guiding mechanical and biological properties in both normal and pathological tendons. Highlighting the organization and spatial distribution of tendon‐containing collagen fibers can be very useful for visualizing a tendon's ultrastructure, biochemical and indirect mechanical properties, which benefits other researchers and clinicians. Picrosirius red (PSR) staining, relying on the birefringence of collagen fibers, is one of the best understood histochemical methods that can highly and specifically underline fibers better than other common staining techniques when combined with polarized light microscopy (PLM). Polarized light microscopy provides complementary information about collagen fibers, such as orientation, type and spatial distribution, which is important for a comprehensive assessment of collagen alteration in a tendon. Here, this brief review serves as a simplistic and important primer to research developments in which differential staining of collagen types by the Picrosirius‐polarization method is increasing in diverse studies of the medical field, mainly in the assessment of the morphology, spatial distribution, and content of collagen in tendons.

Abstract Background The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.

Abstract More and more studies report that exosomes released by various cells can serve as a medium for information exchange between different cells. Through a deep understanding of the physical and chemical properties of exosomes, the researchers revealed a more precise molecular mechanism of its participation in the process of intercellular communication. In particular, microRNA (miRNA) is found inside exosomes, as well as long noncoding RNA (lncRNA). Extensive evidence indicates that exosomal miRNAs participates in the occurrence and development of lung cancer and plays a variety of roles. Therefore, the release of RNA‐containing exosomes in many different kinds of body fluids has caused widespread interest among researchers. In this review, we report evidence from human studies involving miRNAs and other ncRNAs in exosomes associated with lung cancer as diagnostic and prognostic markers. Currently, there is a small amount of evidence that exosomal miRNAs can be used as early diagnosis and prognostic markers for lung cancer, and their exact role in lung cancer patients still needs further study.

Abstract The intestinal microbiota plays an important role in the health and metabolism of the host. Next‐generation sequencing technology has enabled the characterization of the gut microbiota of several animal species. We analyzed the intestinal microbiota in six different parts of the gastrointestinal tracts (GITs) of five Mongolian horses by sequencing the 16S rRNA gene V3‐V4 hypervariable region. All horses were kept in the natural habitat of the Inner Mongolia grassland. Significant differences were observed among the microbiota compositions of the distinct GIT regions. In addition, while the microbial community structures of the small and large intestine were significantly different, those of the cecum and colon were similar. In the foregut, Firmicutes (65%) and Proteobacteria (23%) were the most abundant, while Firmicutes (45%) and Bacteroidetes (42%) were the most common in the hindgut. At the level of family, Ruminococcaceae (p = .203), Lachnospiraceae (p = .157), Rikenellaceae (p = .122), and Prevotellaceae (p = .068) were predominant in the hindgut, while the relative abundance of the Akkermansia genus (5.7%, p = .039) was higher in the ventral colon. In terms of the putative functions, the ratio of microbial abundance in the different parts of the GIT was similar, the result can help characterize the gut microbial structure of different animals.

Abstract Regional hybrid energy system (RHES) is an effective way to accommodate clean energy and reduce its uncertainty. It is also an important development direction for energy market reform, playing an important role in the field of energy supply and demand. Based on electricity price, thermal price, and the relationship between load supply and demand, the paper proposes an optimal scheduling model for regional energy systems to promote clean energy consumption. Firstly, the typical structure and system modules of the integrated regional energy system are introduced in detail, and the two subsystem operating models of electricity and heating are given. Secondly, a multi‐objective function that combines the economics and stability of the system is constructed. The model maximizes the economic benefits and minimizes the net load fluctuations on the basis of maximizing the consumption of clean energy. The multi‐objective singularity is realized by fuzzy membership function. The decision‐making risk caused by the uncertainty of clean energy output is analyzed by introducing robust optimization theory. Finally, the effectiveness of the proposed model is verified based on a region in northwestern China. The results show that the proposed multi‐objective model can combine different optimization demands together, maximize the economic characteristics of clean energy while properly controlling risks, and provide reasonable support for decision makers to develop optimal operation plans.

Abstract Microplastics are an emergent yet critical issue for the environment because of high degradation resistance and bioaccumulation. Unfortunately, the current technologies to remove, recycle, or degrade microplastics are insufficient for complete elimination. In addition, the fragmentation and degradation of mismanaged plastic wastes in environment have recently been identified as a significant source of microplastics. Thus, the developments of effective microplastics removal methods, as well as, plastics recycling strategies are crucial to build a microplastics‐free environment. Herein, this review comprehensively summarizes the current technologies for eliminating microplastics from the environment and highlights two key aspects to achieve this goal: 1) Catalytic degradation of microplastics into environmentally friendly organics (carbon dioxide and water); 2) catalytic recycling and upcycling plastic wastes into monomers, fuels, and valorized chemicals. The mechanisms, catalysts, feasibility, and challenges of these methods are also discussed. Novel catalytic methods such as, photocatalysis, advanced oxidation process, and biotechnology are promising and eco‐friendly candidates to transform microplastics and plastic wastes into environmentally benign and valuable products. In the future, more effort is encouraged to develop eco‐friendly methods for the catalytic conversion of plastics into valuable products with high efficiency, high product selectivity, and low cost under mild conditions.

With the development and application of a bionic flapping micro aircraft vehicle (FMAV), further requirements for its high maneuvering flight characteristics have been put forward. A controlling tail cannot meet the requirements of the maneuvering flight of insect-sized FMAVs, and it has become necessary to find new mechanisms for high maneuvering flight. In this study, two flapping mechanisms with movable hinges based on a double crank rocker mechanism (DCRM) and a single crank slider mechanism (SCSM) are proposed. The instantaneous flapping angles, their extremum and means, and the flapping amplitudes of the two mechanisms are studied for various hinge offsets. A comparison between these two mechanisms indicates that the mechanism based on SCSM is more appropriate in providing adjustable flapping amplitudes for lateral wings. Finally, a dragonfly-like prototype assembled using a carbon fiber plate with adjustable wings is designed and manufactured based on the SCSM. Flight tests are conducted to show that the rack and pinion mechanism can accomplish the movement of hinges neatly, and the proposed flapping mechanism makes left turns and right turns effectively while continuing to fly forward. The prototype is good in terms of crashworthiness and the replacement of components, and it offers an easy and reliable technique for the maneuvering flight of FMAVs.

Abstract With the promulgation and implementation of a large number of renewable energy policies in China, the rapid development of renewable energy is accompanied by the prominent phenomenon of renewable energy abandoning wind and light. Energy storage technology is the key technology to promote the consumption of renewable energy. The government can promote the energy storage technology through the incentive policy of energy storage industry. Firstly, content analysis method is used to analyze China's energy storage policy, and five incentive policies for promoting energy storage technology are obtained. Secondly, built a game model of energy storage technology promotion based on the evolutionary game theory. Finally, use MATLAB software for numerical simulation. Numerical simulation results show that: (a) When the local government chooses to promote less, energy enterprises will eventually adopt the nonconfigure strategy; (b) when the local government chooses to promote more vigorously, energy enterprises will finally adopt the configure strategy; (c) increase in the total electricity sold by energy enterprises with energy storage devices, the sales price of energy stored per unit, the compensation price of energy stored per unit, tax relief standards, and incentive costs of local governments can promote energy enterprises to choose configure strategies; and (d) the reduction of unit energy storage cost, configure cost, and comprehensive tax rate can promote energy enterprises to choose configure strategy.

Abstract Recognition of specific antigens expressed in cancer cells is the initial process of cytolytic T cell‐mediated cancer killing. However, this process can be affected by other non‐cancerous cellular components in the tumor microenvironment. Here, it is shown that interleukin‐33 (IL‐33)‐activated macrophages protect melanoma cells from tumor‐infiltrating lymphocyte‐mediated killing. Mechanistically, IL‐33 markedly upregulates metalloprotease 9 (MMP‐9) expression in macrophages, which acts as a sheddase to trim NKG2D, an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, subsets of CD4+ T cells, iNKT cells, and γδ T cells. Further, MMP‐9 also cleaves the MHC class I molecule, cell surface antigen‐presenting complex molecules, expressed in melanoma cells. Consequently, IL‐33‐induced macrophage MMP‐9 robustly mitigates the tumor killing‐effect by T cells. Genetic and pharmacological loss‐of‐function of MMP‐9 sheddase restore T cell‐mediated cancer killing. Together, these data provide compelling in vitro and in vivo evidence showing novel mechanisms underlying the IL‐33‐macrophage‐MMP‐9 axis‐mediated immune tolerance against cancer cells. Targeting each of these signaling components, including IL‐33 and MMP‐9 provides a new therapeutic paradigm for improving anticancer efficacy by immune therapy.

Abstract Aim Drug‐resistant epilepsy (DRE), most subsequently developing refractory epilepsy, causes a significant burden to the society. microRNAs have been demonstrated as key regulators and therapeutic targets in epilepsy. Accordingly, the aim of the present study was to test whether miR‐485 could be a potential target for DRE. Methods and results An in vivo DRE model was developed in Sprague–Dawley rats by lithium chloride‐pilocarpine and screened by antiepileptic drugs. We found that miR‐485‐5p in hippocampus was significant downregulated at early stage and recovered to normal level at late stage of DRE. Overexpression of miR‐485‐5p in dentate gyrus (DG) of hippocampus in DRE rats could significantly decrease the frequency of seizures and the numbers of epileptiform spikes of hippocampal DG neuron, and could specifically decrease SV2A expression without affecting PSD‐95 expression in DG. Furthermore, miR‐485‐5p overexpression could significantly downregulate the expression of efflux transporter related to multidrug resistance (ABCC1) in hippocampus at late stage of DRE. Finally, a specific expression pattern of neuronal signaling‐transduction proteins (LRP4, MDM4, p53, and TMBIM1) for DRE was observed, and miR‐485‐5p overexpression could modulate these proteins’ expression levels toward normal in hippocampus both at early and late stage of DRE. Conclusion Collectively, these results suggest that miR‐485 was a potential target for anti‐DRE, and this effects might be partially via miR‐485‐5p/homeostatic‐synaptic plasticity‐molecule axis and/or targeting efflux transporter (ABCC1) and other neuronal signaling‐transduction proteins (LRP4, MDM4, p53, and TMBIM1).

Abstract Two‐dimensional (2D) transition metal dichalcogenides (TMDCs) with unique electrical properties are fascinating materials used for future electronics. However, the strong Fermi level pinning effect at the interface of TMDCs and metal electrodes always leads to high contact resistance, which seriously hinders their application in 2D electronics. One effective way to overcome this is to use metallic TMDCs or transferred metal electrodes as van der Waals (vdW) contacts. Alternatively, using highly conductive doped TMDCs will have a profound impact on the contact engineering of 2D electronics. Here, a novel chemical vapor deposition (CVD) using mixed molten salts is established for vapor–liquid–solid growth of high‐quality rhenium (Re) and vanadium (V) doped TMDC monolayers with high controllability and reproducibility. A tunable semiconductor to metal transition is observed in the Re‐ and V‐doped TMDCs. Electrical conductivity increases up to a factor of 108 in the degenerate V‐doped WS2 and WSe2. Using V‐doped WSe2 as vdW contact, the on‐state current and on/off ratio of WSe2‐based field‐effect transistors have been substantially improved (from ≈10–8 to 10–5 A; ≈104 to 108), compared to metal contacts. Future studies on lateral contacts and interconnects using doped TMDCs will pave the way for 2D integrated circuits and flexible electronics.

Abstract Background The use of alpha‐fetoprotein (AFP) testing for the surveillance, diagnosis, and prognosis of hepatocellular carcinoma (HCC) remains controversial. Here, we compared AFP testing rates, elevated AFP rates, factors associated with elevated AFP levels, and prognostic factors associated with overall survival (OS) in HCC patients from different ethnic groups. Methods Patients with HCC were identified from the Surveillance, Epidemiology, and End Results registries. Race was categorized as white, black, and others. AFP testing rates and elevated AFP rates were analyzed. Multivariable logistic regression and Cox regression analyses were used to identify independent factors associated with elevated AFP levels and prognosis, respectively. All statistical tests were two sided. Results A proportion of 79.2% of total HCC patients had AFP testing reports; 77.3% of white, 79.7% of black, and 81.2% of other races underwent AFP testing. Compared with white and other races, black HCC patients had a higher rate of elevated AFP levels among all patients and the early‐stage HCC patient cohort. Elevated AFP level was a significant prognostic factor for all HCC patients in different race groups. Factors associated with elevated AFP level and prognostic factors associated with OS varied significantly by race. Conclusions AFP testing, elevated AFP rates, predictors of elevated AFP level, and prognostic factors associated with OS differed significantly according to race after adjusting for AFP levels among the three groups. AFP testing for the surveillance, diagnosis, and prognosis of HCC patients is strongly recommended, although racial disparities need to be considered.

Class III medical devices are defined as those which are implanted inside the human body and applied to maintain normal life and retain original tissue or organic functions. Because these devices are associated with high risk, their effectiveness and safety should be strictly monitored and clinically investigated. The aim of clinical investigation of these medical devices is to ensure the acceptability of their effectiveness and safety levels. On designing the clinical trial, the investigator should determine the indices to assess the effectiveness and safety of medical devices, select reasonable data‐analyzing methods, and pay attention to several other issues. Although some guidelines on specific class III medical devices have illustrated those aspects in detail, there is still no comprehensive report that details all those principles and methodologies. This article aims to summarize the common features among the instruction principles and provide technological support for the clinical study of class III medical devices.