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Abstract Background The ability of bronchial amylase level for predicting ventilator associated pneumonia (VAP) has been extensively studied with conflicting results. This meta-analysis aimed to explore the value of bronchial amylase for predicting VAP in intubated adults. Methods PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to November 2023. The diagnostic odds ratio (DOR), sensitivity, and specificity were calculated. The summary receiver operating characteristic curve was estimated, and the area under the curve (AUROC) was calculated. Results Overall, six studies including 769 patients were included in this review, of whom 273 (36%) were developed VAP. The cutoff values of bronchial amylase level were ranged from 8.1 U/L to 4681.5U/L. Heterogeneity between studies was assessed with an overall Q = 1.99, I 2 = 0, and P = 0.185, The pooled sensitivity and specificity for the overall population were 0.78 [95% confidence interval (CI) 0.67–0.86] and 0.75(95% CI 0.56–0.88) respectively. The DOR was 11(95% CI 3.0–40.0). The pooled AUROC was 0.83 (95%CI 0.80–0.86). Conclusions The bronchial amylase is a helpful marker for predicting VAP in intubated adults. However, it cannot be recommended as the single definitive test for VAP, but rather it must be interpreted in context with information from careful medical history, physical examination, and when feasible, microbiological assessment.

To explore fracturing technology for vertical wells in ultra-shallow shale gas reservoirs, a coupled thermo-hydro-mechanical-damage (THM-D) fracturing and production integration model is established in this study. In addition, a new coupled hydro-mechanical damage model is established to calculate fracture evolution. These two models are validated through theoretical models and field data, respectively. Based on these models, the quality of fracturing under different geological parameters, fracturing parameters, and fracturing technology is compared and analyzed. The results show that the distribution of natural fractures significantly influences fracturing and production. In addition, due to the high leak-off in the ultra-shallow shale reservoir, the total fracture length and cumulative production after 720 days of carbon dioxide fracturing are only 70.35% and 77.26% of the values achieved by hydraulic fracturing, respectively. Therefore, it is necessary to consider reducing carbon dioxide leak-off in the design of carbon dioxide fracturing in ultra-shallow shale reservoirs. Fracturing efficiency also should be considered when designing fracturing time. When the injection rate is 5 m3/min, the efficiency drops sharply if the fracturing time exceeds 67.45 min. The production of hydraulic fracturing and carbon dioxide fractured wells has also been studied when fracturing methods without proppant are used. This study found that a satisfactory production rate can also be achieved in ultra-shallow shale gas reservoirs when fracturing without proppant.

Abstract In recent years, development in high‐throughput sequencing technologies has experienced an increasing application of statistics, pattern recognition, and machine learning in bioinformatics analyses. SangeBox platform to meet different scientific demands. The new version of Sangs is a widely used tool among many researchers, which encourages us to continuously improve the plerBox 2 (http://vip.sangerbox.com) and extends and optimizes the functions of interactive graphics and analysis of clinical bioinformatics data. We introduced novel analytical tools such as random forests and support vector machines, as well as corresponding plotting functions. At the same time, we also optimized the performance of the platform and fixed known problems to allow users to perform data analyses more quickly and efficiently. SangerBox 2 improved the speed of analysis, reduced resource required for computer performance, and provided more analysis methods, greatly promoting the research efficiency.

Abstract Obesity is a metabolic disorder closely associated with profound alterations in gut microbial composition. However, the dynamics of species composition and functional changes in the gut microbiome in obesity remain to be comprehensively investigated. In this study, we conducted a meta-analysis of metagenomic sequencing data from both obese and non-obese individuals across multiple cohorts, totaling 1351 fecal metagenomes. Our results demonstrate a significant decrease in both the richness and diversity of the gut bacteriome and virome in obese patients. We identified 38 bacterial species including Eubacterium sp. CAG:274, Ruminococcus gnavus, Eubacterium eligens and Akkermansia muciniphila, and 1 archaeal species, Methanobrevibacter smithii, that were significantly altered in obesity. Additionally, we observed altered abundance of five viral families: Mesyanzhinovviridae, Chaseviridae, Salasmaviridae, Drexlerviridae, and Casjensviridae. Functional analysis of the gut microbiome indicated distinct signatures associated to obesity and identified Ruminococcus gnavus as the primary driver for function enrichment in obesity, and Methanobrevibacter smithii, Akkermansia muciniphila, Ruminococcus bicirculans, and Eubacterium siraeum as functional drivers in the healthy control group. Additionally, our results suggest that antibiotic resistance genes and bacterial virulence factors may influence the development of obesity. Finally, we demonstrated that gut vOTUs achieved a diagnostic accuracy with an optimal area under the curve of 0.766 for distinguishing obesity from healthy controls. Our findings offer comprehensive and generalizable insights into the gut bacteriome and virome features associated with obesity, with the potential to guide the development of microbiome-based diagnostics.

ABSTRACTMyotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

ABSTRACTThis study investigated resistance evolution mechanisms of conjugated plasmids and bacterial hosts under different concentrations of antibiotic pressure. Ancestral strain ECNX52 was constructed by introducing the blaNDM-5-carrying IncX3 plasmid into E. coli C600, and was subjected to laboratory evolution under different concentrations of meropenem pressure. Minimal inhibitory concentrations and conjugation frequency were determined. Fitness of these strains was assessed. Whole genome sequencing and transcriptional changes were performed. Ancestral host or plasmids were recombined with evolved hosts or plasmids to verify plasmid or host factors in resistance evolution. Role of the repA mutation on plasmid copy number was determined. Two out of the four clones (EM2N1 and EM2N3) exhibited four-fold increase in MIC when exposed to a continuous pressure of 2 μg/mL MEM (1/32 MIC), by down regulating expression of outer membrane protein ompF. Besides, all four clones displayed four-fold increase in MIC and higher conjugation frequency when subjected to a continuous pressure of 4 μg/mL MEM (1/16 MIC), attributing to increasing plasmid copy number generated by repA D140Y (GAT→TAT) mutation. Bacterial hosts and conjugative plasmids can undergo resistance evolution under certain concentrations of antimicrobial pressure by reducing the expression of outer membrane proteins or increasing plasmid copy numbers.

ABSTRACTThe human gut microbiota constitutes a vast and complex community of microorganisms. The myriad of microorganisms present in the intestinal tract exhibits highly intricate interactions, which play a crucial role in maintaining the stability and balance of the gut microbial ecosystem. These interactions, in turn, influence the overall health of the host. The mammalian gut microbes have evolved a wide range of mechanisms to suppress or even eliminate their competitors for nutrients and space. Simultaneously, extensive cooperative interactions exist among different microbes to optimize resource utilization and enhance their own fitness. This review will focus on the competitive mechanisms among members of the gut microorganisms and discuss key modes of actions, including bacterial secretion systems, bacteriocins, membrane vesicles (MVs) etc. Additionally, we will summarize the current knowledge of the often-overlooked positive interactions within the gut microbiota, and showcase representative machineries. This information will serve as a reference for better understanding the complex interactions occurring within the mammalian gut environment. Understanding the interaction dynamics of competition and cooperation within the gut microbiota is crucial to unraveling the ecology of the mammalian gut microbial communities. Targeted interventions aimed at modulating these interactions may offer potential therapeutic strategies for disease conditions.

Abstract Astaxanthin (ASX) is an oxygen‐containing non‐vitamin A carotenoid pigment. However, the role of ASX in autoimmune hepatitis (AIH) remains unclear. In this study, a mouse model of AIH is established induced by concanavalin A (ConA). Mass cytometry and single‐cell RNA sequencing (scRNA‐seq) are used to analyze the potential role of ASX in regulating the immune microenvironment of AIH. ASX treatment effectively alleviated liver damage induced by ConA and downregulated pro‐inflammatory cytokines production in mice. Mass cytometry and scRNA‐seq analyses revealed a significant increase in the number of CD8+ T cells following ASX treatment. Functional markers of CD8+ T cells, such as CD69, MHC II, and PD‐1, are significantly downregulated. Additionally, specific CD8+ T cell subclusters (subclusters 4, 13, 24, and 27) are identified, each displaying distinct changes in marker gene expression after ASX treatment. This finding suggests a modulation of CD8+ T cell function by ASX. Finally, the key transcription factors for four subclusters of CD8+ T cells are predicted and constructed a cell‐to‐cell communication network based on receptor‐ligand interactions probability. In conclusion, ASX holds the potential to ameliorate liver damage by regulating the number and function of CD8+ T cells.

The stimulator of interferon genes (STING), an integral adaptor protein in the DNA-sensing pathway, plays a pivotal role in the innate immune response against infections. Additionally, it presents a valuable therapeutic target for infectious diseases and cancer. We observed that fangchinoline (Fan), a bis-benzylisoquinoline alkaloid (BBA), effectively impedes the replication of vesicular stomatitis virus (VSV), encephalomyocarditis virus (EMCV), influenza A virus (H1N1), and herpes simplex virus-1 (HSV-1) in vitro. Fan treatment significantly reduced the viral load, attenuated tissue inflammation, and improved survival in a viral sepsis mouse model. Mechanistically, Fan activates the antiviral response in a STING-dependent manner, leading to increased expression of interferon (IFN) and interferon-stimulated genes (ISGs) for potent antiviral effects in vivo and in vitro. Notably, Fan interacts with STING, preventing its degradation and thereby extending the activation of IFN-based antiviral responses. Collectively, our findings highlight the potential of Fan, which elicits antiviral immunity by suppressing STING degradation, as a promising candidate for antiviral therapy.

Abstract Hepatocellular carcinoma (HCC) is the third leading cause of global cancer-related deaths. Despite immunotherapy offering hope for patients with HCC, only some respond to it. However, it remains unclear how to pre-screen eligible patients. Our study aimed to address this issue. In this study, we identified 13 prognostic genes through univariate Cox regression analysis of 87 apoptosis-related genes. Subsequently, these 13 genes were analyzed using ConsensusClusterPlus, and patients were categorized into three molecular types: C1, C2, and C3. A prognostic model and RiskScore were constructed using Lasso regression analysis of 132 significant genes identified between C1 and C3. We utilized quantitative polymerase chain reaction to confirm the model’s transcript level in Huh7 and THLE2 cell lines. Both molecular subtypes and RiskScores effectively predicted patients benefiting from immunotherapy. Cox regression analysis revealed RiskScore as the most significant prognosis factor, suggesting its clinical application potential and providing a foundation for future experimental research.

Objective: Few studies use all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules. Methods: The RFA indications for MNG include 2–5 benign nodules with over 50% normal tissue on ultrasound, 1–3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable to undergo surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months, and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD), and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules that newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm. Results: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38 ± 13.75 months (range, 12–60 months), the volume reduction rate of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. Of the patients, 9.7% (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185). Conclusion: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is a useful minimally invasive treatment modality for selected MNG patients.

In this paper, we consider a dual-band communication system, where a base station (BS) can communicate with a user equipment (UE) over either the sub-6GHz band or the millimeter wave (mmWave) band. We consider the joint detection of the blockage status of the BS-UE link and the optimization of the downlink rate through frequency band scheduling and beamforming design. Typically, the blockage detection requires the transmission and detection of an echo signal, and the downlink beamforming design relies on the estimation of the channel state information (CSI) of the downlink sub-6GHz and mmWave bands, the acquisition of which may result in high complexity and large overhead. To address these problems, we investigate solving the problem using only the CSI of the uplink sub-6GHz band. We decompose the problem into a blockage detection sub-problem and a beamforming design sub-problem. For the former sub-problem, we propose an efficient algorithm based on the convolutional neural network (CNN) technique. For the latter sub-problem, we propose an algorithm based on the MobileNetV2 module to achieve a high learning efficiency. Simulation results show that the proposed blockage detection algorithm can achieve over 99% detection accuracy, and the proposed beamforming design algorithm can achieve over 10% downlink rate gain, as compared to several benchmark schemes.

In this paper, we consider a system that integrates an unmanned aerial vehicle (UAV) for sensing and communication. The UAV is responsible for communication with multiple users and sensing targets for multiple users. Our objective is to minimize the age of information (AoI) of the sensory data by jointly optimizing the scheduling, transmit beamforming, trajectory, and transmit power of the UAV, while considering the communication quality constraints and physical constraints. To solve the optimization problem in a low-complexity manner, we first derive a closed-form solution for the transmit beamforming. Then, we decompose the remaining problem into two subproblems: one focuses on maximizing the total amount of the target sensing time, while the other aims to minimize the total amount of the sensing task completion time. For the former subproblem, we propose a low-complexity chain-based algorithm. For the latter subproblem, we utilize the Lagrange dual method and successive convex approximation technique. Simulation results show that our proposed algorithm can achieve a smaller average AoI with a low complexity compared to benchmark schemes.

Abstract Medical image segmentation is a critical component in clinical practice, facilitating accurate diagnosis, treatment planning, and disease monitoring. However, existing methods, often tailored to specific modalities or disease types, lack generalizability across the diverse spectrum of medical image segmentation tasks. Here we present MedSAM, a foundation model designed for bridging this gap by enabling universal medical image segmentation. The model is developed on a large-scale medical image dataset with 1,570,263 image-mask pairs, covering 10 imaging modalities and over 30 cancer types. We conduct a comprehensive evaluation on 86 internal validation tasks and 60 external validation tasks, demonstrating better accuracy and robustness than modality-wise specialist models. By delivering accurate and efficient segmentation across a wide spectrum of tasks, MedSAM holds significant potential to expedite the evolution of diagnostic tools and the personalization of treatment plans.

Abstract Polyamines are essential for the growth and proliferation of mammalian cells and are intimately involved in biological mechanisms such as DNA replication, RNA transcription, protein synthesis, and post-translational modification. These mechanisms regulate cellular proliferation, differentiation, programmed cell death, and the formation of tumors. Several studies have confirmed the positive effect of polyamines on the maintenance of health, while others have demonstrated that their activity may promote the occurrence and progression of diseases. This review examines a variety of topics, such as polyamine source and metabolism, including metabolism, transport, and the potential impact of polyamines on health and disease. In addition, a brief summary of the effects of oncogenes and signaling pathways on tumor polyamine metabolism is provided. Video Abstract

The injection volume and the distribution of a proppant inside a fracture have a direct impact on the stimulation effect of fracturing. In this study, a new proppant transport model was established based on the Euler method. In this model, the proppant plugging element allows fluid to pass through. Furthermore, the proppant plugging process was successfully simulated based on this model. The proppant transport and ultimate injection concentration under different injection modes were discussed. The numerical simulation results indicate that compared with the strategy of constant concentration, the strategy of a stepwise increasing concentration can make the proppant distribution in the fracture more uniform. The strategy of injection with a stepwise increasing concentration and a periodic injection with a stepwise increasing concentration can increase the injection volume of the proppant by 25%. In the fracture network, a 67% increase in the number of branch fractures resulted in a 17% increase in the maximum proppant injection volume. If the branch fracture width is reduced by 50%, the maximum proppant injection volume is reduced by 17%.

Introduction: Gene-edited pigs have become prominent models for studying human disease mechanisms, gene therapy, and xenotransplantation. CRISPR (clustered regularly interspaced short palindromic repeats)/CRISPR-associated 9 (CRISPR/Cas9) technology is a widely employed tool for generating gene-edited pigs. Nevertheless, delivering CRISPR/Cas9 to pre-implantation embryos has traditionally posed challenges due to its reliance on intricate micromanipulation equipment and specialized techniques, resulting in high costs and time-consuming procedures. This study aims to introduce a novel one-step approach for generating genetically modified pigs by transducing CRISPR/Cas9 components into pre-implantation porcine embryos through oviductal injection of recombinant adeno-associated viruses (rAAV).Methods: We first used rAAV-1, rAAV-6, rAAV-8, rAAV-9 expressing EGFP to screen for rAAV serotypes that efficiently target porcine embryos, and then, to achieve efficient expression of CRISPR/Cas9 in vivo for a short period, we packaged sgRNAs targeting the GHR genes to self-complementary adeno-associated virus (scAAV), and Cas9 proteins to single-stranded adeno-associated virus (ssAAV). The efficiency of porcine embryos -based editing was then validated in vitro. The feasibility of this one-step method to produce gene-edited pigs using rAAV-CRISPR/Cas9 oviductal injection into sows within 24 h of conception was then validated.Results: Our research firstly establishes the efficient delivery of CRISPR/Cas9 to pig zygotes, both in vivo and in vitro, using rAAV6. Successful gene editing in pigs was achieved through oviductal injection of rAAV-CRISPR/Cas9.Conclusion: This method circumvents the intricate procedures involved in in vitro embryo manipulation and embryo transfers, providing a straightforward and cost-effective approach for the production of gene-edited pigs.

Abstract Non-coding RNA has aroused great research interest recently, they play a wide range of biological functions, such as regulating cell cycle, cell proliferation, and intracellular substance metabolism. Piwi-interacting RNAs (piRNAs) are emerging small non-coding RNAs that are 24–31 nucleotides in length. Previous studies on piRNAs were mainly limited to evaluating the binding to the PIWI protein family to play the biological role. However, recent studies have shed more lights on piRNA functions; aberrant piRNAs play unique roles in many human diseases, including diverse lethal cancers. Therefore, understanding the mechanism of piRNAs expression and the specific functional roles of piRNAs in human diseases is crucial for developing its clinical applications. Presently, research on piRNAs mainly focuses on their cancer-specific functions but lacks investigation of their expressions and epigenetic modifications. This review discusses piRNA’s biogenesis and functional roles and the recent progress of functions of piRNA/PIWI protein complexes in human diseases. Video Abstract

Abstract Background Whole-cell biocatalysis has been exploited to convert a variety of substrates into high-value bulk or chiral fine chemicals. However, the traditional whole-cell biocatalysis typically utilizes the heterotrophic microbes as the biocatalyst, which requires carbohydrates to power the cofactor (ATP, NAD (P)H) regeneration. Results In this study, we sought to harness purple non-sulfur photosynthetic bacterium (PNSB) as the biocatalyst to achieve light-driven cofactor regeneration for cascade biocatalysis. We substantially improved the performance of Rhodopseudomonas palustris-based biocatalysis using a highly active and conditional expression system, blocking the side-reactions, controlling the feeding strategy, and attenuating the light shading effect. Under light-anaerobic conditions, we found that 50 mM ferulic acid could be completely converted to vanillyl alcohol using the recombinant strain with 100% efficiency, and > 99.9% conversion of 50 mM p-coumaric acid to p-hydroxybenzyl alcohol was similarly achieved. Moreover, we examined the isoprenol utilization pathway for pinene synthesis and 92% conversion of 30 mM isoprenol to pinene was obtained. Conclusions Taken together, these results suggested that R. palustris could be a promising host for light-powered biotransformation, which offers an efficient approach for synthesizing value-added chemicals in a green and sustainable manner. Graphical Abstract

The utilization of dredged sediment (DS) as a transformative material in building applications presents an ideal consumption strategy. This study endeavors to create a novel ceramsite lightweight aggregate (LWA) through the co-sintering of DS and rice husks (RHs), further integrating this LWA into the construction of pervious concrete. Results revealed that the optimum production procedure for the DS-based LWA incorporated a 21% RH addition, a sintering temperature of 1100 °C, and a sintering duration of 21 min. Notably, the optimal ceramsite LWA, denoted as SDC-H, exhibited a cylinder compressive strength of 28.02 MPa and an adsorption efficiency for Pb2+ of 94.33%. Comprehensive analysis (encompassing bulk density, cylinder compressive strength, water absorption, and the leaching concentrations of heavy metals) confirmed that SDC-H impacted the specification threshold of high-strength light aggregate derived from solid waste (T/CSTM 00548-2022). Substituting 50% of SDC-H led to a diminution in the mechanical properties but an improvement in the dynamic adsorption capacity of the innovative pervious concrete, registering a mechanical strength of 26.25 MPa and a cumulative adsorption capacity for Pb2+ of 285 mg/g. These performances of pervious concrete containing 50% SDC-H might correlate with the evolution of an interconnected and open-pore structure.

Abstract Background Decompensated liver cirrhosis (DLC), a terminal-stage complication of liver disease, is a major cause of morbidity and mortality in patients with hepatopathies. Human umbilical cord mesenchymal stem cell (hUCMSC) therapy has emerged as a novel treatment alternative for the treatment of DLC. However, optimized therapy protocols and the associated mechanisms are not entirely understood. Methods We constructed a DLC rat model consistent with the typical clinical characteristics combined use of PB and CCL4. Performing dynamic detection of liver morphology and function in rats for 11 weeks, various disease characteristics of DLC and the therapeutic effect of hUCMSCs on DLC in experimental rats were thoroughly investigated, according to ascites examination, histopathological, and related blood biochemical analyses. Flow cytometry analysis of rat liver, immunofluorescence, and RT-qPCR was performed to examine the changes in the liver immune microenvironment after hucMSCs treatment. We performed RNA-seq analysis of liver and primary macrophages and hUCMSCs co-culture system in vitro to explore possible signaling pathways. PPARγ antagonist, GW9662, and clodronate liposomes were used to inhibit PPAR activation and pre-exhaustion of macrophages in DLC rats’ livers, respectively. Results We found that changing the two key issues, the frequency and initial phase of hUCMSCs infusion, can affect the efficacy of hUCMSCs, and the optimal hUCMSCs treatment schedule is once every week for three weeks at the early stage of DLC progression, providing the best therapeutic effect in reducing mortality and ascites, and improving liver function in DLC rats. hUCMSCs treatment skewed the macrophage phenotype from M1-type to M2-type by activating the PPARγ signaling pathway in the liver, which was approved by primary macrophages and hUCMSCs co-culture system in vitro. Both inhibition of PPARγ activation with GW9662 and pre-exhaustion of macrophages in DLC rats’ liver abolished the regulation of hUCMSCs on macrophage polarization, thus attenuating the beneficial effect of hUCMSCs treatment in DLC rats. Conclusions These data demonstrated that the optimal hUCMSCs treatment effectively inhibits the ascites formation, prolongs survival and significantly improves liver structure and function in DLC rats through the activation of the PPARγ signaling pathway within liver macrophages. Our study compared the efficacy of different hUCMSCs infusion regimens for DLC, providing new insights on cell-based therapies for regenerative medicine.

Multicellular three-dimensional (3D) in vitro models, such as cell spheroids and organoids, can significantly improve the viability, histomorphology, genotype stability, function and drug metabolism of cells [1–3]. In general, several culture methods of 3D models, including the hanging drop, microwell-mesh and hydrogel encapsulating methods, have difficulty building a standard mode and controlling the size and arrangement of cell spheroids or organoids, which could severely affect the authenticity and repeatability of experimental results [4]. Another key factor in 3D in vitro models is the extracellular matrix (ECM), which can determine cell viability, proliferation, differentiation, function, migration and organization [5]. In this study, micropattern array chips combined with decellularized ECM (dECM) not only provide tissue-specific ECM but also control the size and arrangement of 3D models. • Methods have been established to demonstrate the use of dECM as a bioink to generate dECM-coated micropattern array chips by microcontact printing. • The micropattern can limit cell growth and migration, and cells spontaneously assemble into cell spheroids with uniform size and orderly arrangement.

Background: Our previous studies found that autophagy levels in liver and intestinal segments of naturally aging rats were downregulated, and the expression of pro-inflammatory factors was increased. The increased expression of pro-inflammatory factors might be related to the downregulation of autophagy. AMPK is the most critical upstream targeting and regulating molecule of autophagy, and Metformin, as an agonist of AMPK, has the effects of anti-inflammation and anti-aging. We pretreated 29-month-old naturally aging rats with Metformin for a short period and observed the changes in autophagy levels and pro-inflammatory factors in the liver, ileum, and colon after 31 days of intervention and preliminarily investigated the mechanism of its action. Methods: 29-month-old SPF male Wistar rats were divided into three groups: The control group, the Metformin 100 mg/kg intervention group, and the Metformin 250 mg/kg intervention group, with eight rats in each group. At 29 months, different concentrations of Metformin (100 mg/kg, 250 mg/kg) were given by gavage once a day until 30 months, and the control group was kept generally until 30 months. Western Blot was used to assess the expression levels of AMPK, P-AMPK, LC3, and P62 proteins in the liver and intestinal tissues. Intestinal and liver tissues were immunofluorescence labeled for LC3 and P62 proteins. Moreover, RT-qPCR was conducted to detect the expression levels of pro-inflammatory factors IL-1β, TNF-α, IL-6, and MMP-9 mRNA in liver and intestinal tissues. Results: Short-term Metformin pretreatment (31 days) in naturally aging rats (29 months old) increased autophagy levels and down-regulated the expression of various pro-inflammatory cytokines (IL-1β, TNF-α, MMP-9, and IL-6) in various intestinal segments and the liver—the expression of LC3II protein enriched with the increase of Metformin concentration. The level of P62 protein decreased with the accumulation of Metformin concentration. And a higher concentration of Metformin was associated with increased expression of P-AMPK protein. Conclusions: Metformin intervention can boost the autophagy level in the liver and intestine and reduce the expression of aging-related inflammatory factors in aged rats, and these effects may be related to the increase of the AMPK phosphorylation level.

AbstractBackground Peritoneal dialysis (PD)-associated peritonitis is a serious complication observed in peritoneal dialysis patients. Herein, we investigated the clinical characteristics and treatment outcomes of PD peritonitis in patients with different PD durations.Methods All peritonitis episodes from January 2007 to December 2020 at Peking University People’s hospital PD center were retrospectively analyzed and divided into the long-dialysis duration (≥60 months, LDD) and short-dialysis duration (

Abstract Multi-object Tracking is an important issue that has been widely investigated in computer vision. However, in practical applications, moving targets are often occluded due to complex changes in the background, which leads to frequent pedestrian ID switches in multi-object tracking. To solve the problem, we present a multi-object tracking algorithm based on FairMOT and Circle Loss. In this paper, HRNet is adopted as the baseline. Then, Polarized Self-Attention is added to HRNet-w32 to obtain weights of helpful information based on its modeling advantages. Moreover, the re-identification branch is optimized, and the Circle Loss is selected as the loss function to acquire more discriminative pedestrian features and to distinguish different pedestrians. The method proposed is assessed on the public MOT17 datasets. The experimental results show that the MOTA score achieves 69.5%, IDF1 reaches 70.0%, and the number of ID switches (IDs) decreases 636 times compared to the TraDes algorithm.

Abstract Background Intratumoral microbial communities have been recently discovered to exist in a variety of cancers and have been found to be intricately involved in tumour progression. Therefore, investigating the profiles and functions of intratumoral microbial distribution in hepatocellular carcinoma (HCC) is imperative. Methods To verify the presence of microorganisms in HCC, we performed fluorescence in situ hybridization (FISH) using HCC tissues and conducted MiSeq using 99 HCC and paracancerous tissues to identify the key microorganisms and changes in metabolic pathways affecting HCC progression through a variety of bioinformatics methods. Results Microbial diversity was significantly higher in HCC tissues than in adjacent tissues. The abundances of microorganisms such as Enterobacteriaceae, Fusobacterium and Neisseria were significantly increased in HCC tissues, while the abundances of certain antitumour bacteria such as Pseudomonas were decreased. Processes such as fatty acid and lipid synthesis were significantly enhanced in the microbiota in HCC tissues, which may be a key factor through which intratumoral microbes influence tumour progression. There were considerable differences in the microbes and their functions within tumour tissue collected from patients with different clinical features. Conclusion We comprehensively evaluated the intratumoral microbial atlas of HCC tissue and preliminarily explored the mechanism of the effects of the microbial community involving changes in lipid metabolism and effects on HCC progression, which lays the foundation for further research in this field.

Abstract Emerging evidence suggests that epigenetic alterations are responsible for the oncogenesis and progression of cancer. However, the role of epigenetic reprogramming in pancreatic cancer is still not clear. In this study, we used the limma R package to identify differentially expressed protein-coding genes (PCGs) between pancreatic cancer tissues and normal control tissues. The cell-type identification by the estimating relative subsets of RNA transcripts (CIBERSORT) package was used to quantify relative cell fractions in tumors. Prognostic molecular clusters were constructed using ConsensusClusterPlus analysis. Furthermore, the least absolute shrinkage and selection operator and stepAIC methods were used to construct a risk model. We identified 2351 differentially expressed PCGs between pancreatic cancer and normal control tissues in The cancer genome atlas dataset. Combined with histone modification data, we identified 363 epigenetic PCGs (epi-PCGs) and 19,010 non-epi-PCGs. Based on the epi-PCGs, we constructed three molecular clusters characterized by different expression levels of chemokines and immune checkpoint genes and distinct abundances of various immune cells. Furthermore, we generated a 9-gene model based on dysfunctional epi-PCGs. Additionally, we found that patients with high risk scores showed poorer prognoses than patients with low risk scores (p

Fluid shear stress (FSS) regulates the metastasis of hepatocellular carcinoma (HCC), but the role of the RhoA-YAP1-autophagy pathway in HCC remains unclear. Due to the core role of liver cancer stem cells (LCSCs) in HCC metastasis and recurrence, we explored the RhoA-YAP1-autophagy pathway in LCSCs under FSS. Our results indicate that LCSCs have stronger proliferation and cell spheroidization abilities. FSS (1 dyn/cm2) upregulated the migration of LCSCs and autophagy protein markers, inducing LC3B aggregation and autophagosome formation in LCSCs. Mechanistically, FSS promoted YAP1 dephosphorylation and transport to the nucleus, which is mediated by RhoA, inducing autophagy. Finally, inhibition of autophagy suppressed cell migration in LCSCs under FSS. In conclusion, FSS promoted the migration of LCSCs via the RhoA-YAP1-autophagy pathway.

Abstract Aberrant long noncoding RNA (lncRNA) expression and fatty acid signaling dysfunction both contribute to hepatocellular carcinoma (HCC) occurrence and development. However, the relationship and interaction mechanism between lncRNAs and fatty acid signaling in HCC remain unclear. Data regarding RNA expression and clinical outcomes for patients with HCC were obtained from The Cancer Genome Atlas (TCGA), HCCDB, and the Gene Expression Omnibus (GEO) databases. Hallmark pathways were identified using the single-sample gene set enrichment analysis (ssGSEA) method. ConsensusClusterPlus was used to establish a consistency matrix for classifying samples into three subtypes. A risk signature was established, and predictive values for key lncRNAs related to prognosis were evaluated using Kaplan–Meier analysis and receiver operating characteristic curves. The ESTIMATE algorithm, MCP-Counter, and ssGSEA were used to evaluate the characteristics of the tumor immune microenvironment. The CTRP2.0 and PRISM were used to analyze drug sensitivity in HCC subtypes. We discovered seven fatty-acid-associated lncRNAs with predictive prognostic capabilities, including TRAF3IP2-AS1, SNHG10, AL157392.2, LINC02641, AL357079.1, AC046134.2, and A1BG-AS. Three subtypes were obtained, which presented with differences in prognosis, clinical information, mutation features, pathway traits, immune characteristics, and drug sensitivity. The seven key lncRNAs identified in this study might serve as promising biomarkers for predicting prognosis in patients with HCC, and the three HCC subtypes classified according to lncRNA expression profiles could improve HCC classification.

Hexahydromethanocarbazole is a bridged polycyclic scaffold present in drugs and photoactive organic materials, however the efficient synthesis of this scaffold remains challenging. Here, the authors develop a multicomponent reaction cascade via phenylnorbornyl palladium species to generate hexahydromethanocarbazole-based libraries with CYP11B1 inhibition activity.

Abstract Quantitative assessment of urbanization effect on surface air temperature (SAT) change provides crucial basis for formal detection and attribution analyses of climate change. However, debates about urbanization‐related warming bias in documented regional SAT trend still persist, mainly due to different determination of rural stations. Here the urbanization effect on SAT change over the Beijing–Tianjin–Hebei region in China during 1980–2019 is estimated through three kinds of ways (i.e., comparisons between urban and rural stations [arithmetically station‐averaged], urban‐dominated and rural‐dominated patches [patch‐weighted mean], and realistic urban and rural areas [area‐weighted mean]). The last method explicitly takes urban and rural land cover fractions into account when calculating urban/rural and regional mean SAT trends. Urbanization‐induced warming in the annual mean SAT change of urban stations (areas) through the three ways are estimated as 0.159°C, 0.195°C, and 0.138°C per decade, respectively. And urbanization effect on regional averaged annual mean SAT calculated by patch‐weighted and area‐weighted methods are 0.113°C and 0.050°C per decade, respectively, which account for 33.8% and 14.8% of the total regional warming. The urbanization effect on observed SAT change estimated by considering realistic urban/rural land cover proportions is much lower than traditional station‐unweighted way.

Modified sludge biochar, recognized for its notable economic and environmental benefits, demonstrates potential as an effective catalyst for peroxydisulfate (PDS) activation. Nevertheless, the specific mechanisms underlying its catalytic performance require more comprehensive investigation. In this study, a modified biochar (TSBC) doped with oxygen (O) and nitrogen (N) atoms was synthesized from sewage sludge and tannin extract, which significantly enhanced the activation of PDS for the degradation of sulfamethoxazole (SMX). The TSBC/PDS system demonstrated robust performance for SMX degradation, achieving over 90% efficiency over a wide pH range (3–10). Subsequent quenching experiments demonstrated that TSBC predominantly catalyzed PDS to generate O21, which effectively degraded SMX via a non-radical pathway. The O- and N-containing functional groups in TSBC were identified as the primary catalytic sites. Besides, density functional theory (DFT) calculations revealed that the incorporation of graphitic N significantly improved the adsorption capacity of PDS on the TSBC surface. Furthermore, based on the identification of intermediates and theoretical calculations, SMX was degraded mainly by two different pathways: S-N cleavage and O21 oxidation. This study offers a foundational framework for the targeted modification of sludge biochar, thereby expanding its applications.

Abstract Background To study the respective peripheral and systemic mechanisms of action of dexmedetomidine, as adjuvant to regional anesthesia, we compared dexmedetomidine added to ropivacaine for mid-forearm nerve blocks, to either systemic-only dexmedetomidine, and to a control with no dexmedetomidine. Methods Sixty patients undergoing hand surgery were randomly divided into three groups (n = 20 per group). Each group underwent a triple-nerve (median, radial and ulnar) mid-forearm blocks with 0.75% ropivacaine. In the DexP group, 60 µg of dexmedetomidine were added to the anesthetic mixture, while in the DexIV group, they were intravenously infused. Normal saline as a placebo was used, either as adjuvant, or intravenously. All patients underwent also a supraclavicular block with 1.5% lidocaine for tourniquet pain. The main outcomes were the duration of analgesia and the duration of sensory blockade separately for each nerve termination of the upper limb, and the duration of motor blockade of the upper limb. Tolerance was assessed by blood pressure and heart rate, and the report of adverse events. Results Duration of analgesia was longer in the DexP group, in comparison to the two other groups (P

Abstract As one of the most malignant cancers and despite various treatment breakthroughs, the prognosis of hepatocellular carcinoma (HCC) remains unsatisfactory. The immune status of the tumor microenvironment (TME) relates closely to HCC progression; however, the mechanism of immune cell infiltration in the TME remains unclear. In this study, we performed a new combination algorithm on lncRNA expression profile data from the TCGA-LIHC cohort to identify lncRNAs related to immune disorders. We identified 20 immune disorder-related lncRNAs and clustered HCC samples based on these lncRNAs. We identified four clusters with differences in immune cell infiltration and immune checkpoint gene expression. We further analyzed differences between groups 1 and 3 and found that the poor prognosis of group 3 may be due to specific and non-specific immunosuppression of the TME, upregulation of immune checkpoint pathways, and activation of tumor proliferation and migration pathways in group 3. We also developed a prognostic model and verified that it has good stability, effectiveness, and prognostic power. This study provides a basis for further exploration of the immune cell infiltration mechanism in HCC, differential HCC prognosis, and improvement of the efficacy of ICIs for the treatment of HCC.

This paper proposes a flexible eddy current TMR (FEC-TMR) sensor to monitor the internal crack of metal joint structures. First, the finite element model of the FEC-TMR sensor is established to analyze the influence of the sensor’s crack identification sensitivity with internal crack propagation at different depths and determine the optimal location and exciting frequency of the sensor. Then, the optimal longitudinal spacing and exciting frequency of the sensor are tested by experiment. The experimental results are consistent with the simulation results, which verify the correctness of the simulation model. Finally, the experiment is carried out for internal cracks of different depths to verify that the sensor can monitor internal cracks, and the crack identification sensitivity gradually decreases with the increase in the depth of the crack from the surface.

As a prevalent epigenetic modification, the role of m6A has been increasingly highlighted in the alteration of numerous RNAs implicated with multiple biological processes, such as formation, export, translation, and degradation. With further the understanding of m6A, accumulating evidence shows that m6A modification similarly affects metabolic process of non-coding genes. But the specifical interplay of m6A and ncRNAs (non-coding RNAs) in gastrointestinal cancers still lacks complete discussion. Thus, we analyzed and summarized how ncRNAs affect the regulators of m6A and by what means the expression of ncRNAs is altered via m6A in gastrointestinal cancers. We focused on the effect of the interaction of m6A and ncRNAs on the molecular mechanisms of malignant behavior in gastrointestinal cancers, revealing more possibilities of ncRNAs for diagnosis and treatment in term of epigenetic modification.

Abstract Pancreatic adenocarcinoma (PAAD) is the most malignant digestive tumor. The global incidence of pancreatic cancer has been rapidly trending upwards, necessitating an exploration of potential prognostic biomarkers and mechanisms of disease development. One of the most prevalent RNA modifications is 5-methylcytosine (m5C); however, its contribution to PAAD remains unclear. Data from The Cancer Genome Atlas (TCGA) database, including genes, copy number variations (CNVs), and simple nucleotide variations (SNVs), were obtained in the present study to identify gene signatures and prognostic values for m5C regulators in PAAD. Regulatory gene m5C changes were significantly correlated with TP53, BRCA1, CDKN2A, and ATM genes, which play important roles in PAAD pathogenesis. In particular, there was a significant relationship between m5C regulatory gene CNVs, especially in genes encoding epigenetic “writers”. According to m5C-regulated gene expression in clinically graded cases, one m5C-regulated genes, DNMT3A, showed both a strong effect on CNVs and a significant correlation between expression level and clinical grade (P

PurposeNephron-sparing surgery (NSS) is a mainstream treatment for localized renal tumors. Segmental renal artery clamping (SRAC) is commonly used in NSS. Automatic and precise segmentations of renal artery trees are required to improve the workflow of SRAC in NSS. In this study, we developed a tridimensional kidney perfusion (TKP) model based on deep learning technique to automatically demonstrate renal artery segmentation, and verified the precision and feasibility during laparoscopic partial nephrectomy (PN).MethodsThe TKP model was established based on convolutional neural network (CNN), and the precision was validated in porcine models. From April 2018 to January 2020, TKP model was applied in laparoscopic PN in 131 patients with T1a tumors. Demographics, perioperative variables, and data from the TKP models were assessed. Indocyanine green (ICG) with near-infrared fluorescence (NIRF) imaging was applied after clamping and dice coefficient was used to evaluate the precision of the model.ResultsThe precision of the TKP model was validated in porcine models with the mean dice coefficient of 0.82. Laparoscopic PN was successfully performed in all cases with segmental renal artery clamping (SRAC) under TKP model’s guidance. The mean operation time was 100.8 min; the median estimated blood loss was 110 ml. The ischemic regions recorded in NIRF imaging were highly consistent with the perfusion regions in the TKP models (mean dice coefficient = 0.81). Multivariate analysis revealed that the feeding lobar artery number was strongly correlated with tumor size and contact surface area; the supplying segmental arteries number correlated with tumor size.ConclusionsUsing the CNN technique, the TKP model is developed to automatically present the renal artery trees and precisely delineate the perfusion regions of different segmental arteries. The guidance of the TKP model is feasible and effective in nephron-sparing surgery.

Circular RNAs (circRNAs) are a new series of noncoding RNAs (ncRNAs) that have been reported to be expressed in eukaryotic cells and have a variety of biological functions in the regulation of cancer pathogenesis and progression. The TME, as a microscopic ecological environment, consists of a variety of cells, including tumor cells, immune cells and other normal cells, ECM and a large number of signaling molecules. The crosstalk between circRNAs and the TME plays a complicated role in affecting the malignant behaviors of digestive system cancers. Herein, we summarize the mechanisms underlying aberrant circRNA expression in the TME of the digestive system cancers, including immune surveillance, angiogenesis, EMT, and ECM remodelling. The regulation of the TME by circRNA is expected to be a new therapeutic method.

BackgroundSingle-cell sequencing (SCS) technologies enable analysis of gene structure and expression data at single-cell resolution. However, SCS analysis in pancreatic cancer remains largely unexplored.MethodsWe downloaded pancreatic cancer SCS data from different databases and applied appropriate dimensionality reduction algorithms. We identified 10 cell types and subsequently screened differentially expressed marker genes of these 10 cell types using FindAllMarkers analysis. Also, we evaluated the tumor immune microenvironment based on ESTIMATE and MCP-counter. Statistical enrichment was evaluated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. We used all candidate gene sets in KEGG database to perform gene set enrichment analysis. We used LASSO regression to reduce the number of genes in the pancreatic risk model by R package glmnet, followed by rtPCR to validate the expression of the signature genes in different pancreatic cancer cell lines.ResultsWe identified 15 cell subpopulations by dimension reduction and data clustering. We divided the 15 subpopulations into 10 distinct cell types based on marker gene expression. Then, we performed functional enrichment analysis for the 352 marker genes in pancreatic cancer cells. Based on RNA expression data and prognostic information from TCGA and GEO datasets, we identified 42 prognosis-related genes, including 5 protective genes and 37 high-risk genes, which we used to identified two molecular subtypes. C1 subtype was associated with a better prognosis, whereas C2 subtype was associated with a worse prognosis. Moreover, chemokine and chemokine receptor genes were differentially expressed between C1 and C2 subtypes. Functional and pathway enrichment uncovered functional differences between C1 and C2 subtype. We identified eight genes that could serve as potential biomarkers for prognosis prediction in pancreatic cancer patients. These genes were used to establish an 8-gene pancreatic cancer prognostic model.ConclusionsWe established an 8-gene pancreatic cancer prognostic model. This model can meaningfully predict prognosis and treatment response in pancreatic cancer patients.

Abstract Background 5-Methylcytosine (m5C) is a reversible modification to both DNA and various cellular RNAs. However, its roles in developing human cancers are poorly understood, including the effects of mutant m5C regulators and the outcomes of modified nucleobases in RNAs. Methods Based on The Cancer Genome Atlas (TCGA) database, we uncovered that mutations and copy number variations (CNVs) of m5C regulatory genes were significantly correlated across many cancer types. We then assessed the correlation between the expression of individual m5C regulators and the activity of related hallmark pathways of cancers. Results After validating m5C regulators’ expression based on their contributions to cancer development and progression, we observed their upregulation within tumor-specific processes. Notably, our research connected aberrant alterations to m5C regulatory genes with poor clinical outcomes among various tumors that may drive cancer pathogenesis and/or survival. Conclusion Our results offered strong evidence and clinical implications for the involvement of m5C regulators.

Abstract Weedy rice is a valuable germplasm resource characterized by its high tolerance to both abiotic and biotic stresses. Abscisic acid (ABA) serves as a regulatory signal in plant cells as part of their adaptive response to stress. However, a global understanding of the response of weedy rice to ABA remains to be elucidated. In the present study, the sensitivity to ABA of weedy rice (WR04-6) was compared with that of temperate japonica Shennong9816 (SN9816) in terms of seed germination and post-germination growth via the application of exogenous ABA and diniconazole, an inhibitor of ABA catabolism. Physiological analysis and a transcriptomic comparison allowed elucidation of the molecular and physiological mechanisms associated with continuous ABA and diniconazole treatment. WR04-6 was found to display higher ABA sensitivity than SN9816, resulting in the rapid promotion of antioxidant enzyme activity. Comparative transcriptomic analyses indicated that the number of differentially expressed genes (DEGs) in WR04-6 seedlings treated with 2 μM ABA or 10 μM diniconazole was greater than that in SN9816 seedlings. Genes involved in stress defense, hormone signal transduction, and glycolytic and citrate cycle pathways were highly expressed in WR04-6 in response to ABA and diniconazole. These findings provide new insight into key processes mediating the ABA response between weedy and cultivated rice.

Differential interference contrast (DIC) microscopy is widely used as a high-contrast imaging method for observing transparent biological samples. However, the absence of fringes in DIC images results in phase gradients that cannot be effectively extracted by most phase-shift algorithms, limiting its application in quantitative detection. Therefore, we propose an algorithm based on the 1-norm character of interferograms that can accurately extract phase shifts from a series of interferograms with less than 1/2 fringes. We improved this algorithm by combining the calculated phase shift with the least-squares fitting method to further extract the phase and applied it to quantitative DIC imaging. In contrast to the conventional algorithm, this algorithm can extract the phase gradient in DIC images with unknown phase shifts, thereby eliminating the computational error in the conventional algorithm introduced by imprecise phase shifts. Simulations and experiments demonstrated that the proposed algorithm can perform accurate phase gradient extraction.

Aims: This study aims to evaluate ECM-coated micropattern arrays derived from decellularization of native porcine lungs as a novel three-dimensional cell culture platform. Methods: ECM derived from decellularization of native porcine lungs was exploited to prepare hydrogels. Then, dECM-coated micropattern arrays were fabricated at four different diameters (50, 100, 150 and 200 ​μm) using polydimethylsiloxane (PDMS). Two lung cancer cell lines, A549 and H1299, were tested on a dECM-coated micropattern array as a novel culture platform for cell adhesion, distribution, proliferation, viability, phenotype expression, and drug screening to evaluate the cytotoxicity of paclitaxel, doxorubicin and cisplatin. Results: The ECM derived from decellularization of native porcine lungs supported cell adhesion, distribution, viability and proliferation better than collagen I and Matrigel as the coated matrix on the surface. Moreover, the optimal diameter of the micropattern arrays was 100–150 ​μm, as determined by measuring the morphology, viability, proliferation and phenotype of the cancer cell spheroids. Cell spheroids of A549 and H1299 on dECM-coated micropattern arrays showed chemoresistance to anticancer drugs compared to that of the monolayer. The different distributions of HIF-1α, MCL-1 (in the center) and Ki-67 and MRP2 (in the periphery) of the spheroids demonstrated the good establishment of basal-lateral polarity and explained the chemoresistance phenomenon of spheroids. Conclusions: This novel three-dimensional cell culture platform is stable and reliable for anticancer drug testing. Drug screening in dECM-coated micropattern arrays provides a powerful alternative to existing methods for drug testing and metabolic profiling in the drug discovery process.

Long non-coding RNAs (lncRNAs) play important roles in the occurrence and progression of tumors. Extensive research has contributed to the current understanding of the critical roles played by lncRNAs in various cancers. LncRNA MIR4435-2HG has been found to be crucial in many cancers, such as breast, cervical, colorectal, and gastric cancer. Expression of MIR4435-2HG is generally upregulated in cancers and MIR4435-2HG participates in many biological functions through molecular mechanism of competitive endogenous RNA networks. This review profiles recent research findings on the expression, functions, mechanism, and clinical value of MIR4435-2HG in cancer, and serves as a reference for further MIR4435-2HG-related research and clinical trials.

Abstract Long noncoding RNAs (lncRNAs), are transcripts longer than 200 nucleotides that are considered to be vital regulators of many cellular processes, particularly in tumorigenesis and cancer progression. long intergenic non-protein coding RNA 261 (LINC00261), a recently discovered lncRNA, is abnormally expressed in a variety of human malignancies, including pancreatic cancer, gastric cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, breast cancer, laryngeal carcinoma, endometrial carcinoma, esophageal cancer, prostate cancer, choriocarcinoma, and cholangiocarcinoma. LINC00261 mainly functions as a tumor suppressor that regulates a variety of biological processes in the above-mentioned cancers, such as cell proliferation, apoptosis, motility, chemoresistance, and tumorigenesis. In addition, the up-regulation of LINC00261 is closely correlated with both favorable prognoses and many clinical characteristics. In the present review, we summarize recent research documenting the expression and biological mechanisms of LINC00261 in tumor development. These findings suggest that LINC00261, as a tumor suppressor, has bright prospects both as a biomarker and a therapeutic target.