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Abstract Background The growth of internet use has greatly impacted many societal sectors, including healthcare. However, current evidence about the relationship between internet usage time and public trust on doctors is insufficient. Objective To examine the relationship between the time spent on the internet and the level of trust in doctors, and explore its mechanism. Methods Multiple regression models are employed, utilizing a sample of 19,193 observations from the China Family Panel Studies (CFPS) in 2020. First, we regress the relative trust in doctors compared to trust in strangers on internet usage time. Subsample results across distinct population groups are explored. Second, we examine the mechanism of using the internet as an information channel through the mediation method, and further investigate the role of the internet as a communication platform by analyzing the moderation effects of socializing activity as well as social media engagement. Results We find a significant negative relationship between increased internet usage time and trust in doctors. This correlation remains robust across different model specifications and variable measurements. The negative correlation is more pronounced among population groups who are elderly, male, married, with low educational levels, insured and residing in urban areas. The role of the internet as a source of information is validated as a mechanism producing the negative influence. The role of the internet as a communication platform tends to mitigate the negative consequences of internet usage, as engaging in online socializing activity can have a positive moderation effect. However, for social media engagement, its overall effect on trust in doctors is negative, potentially due to social media’s dual function as a communication platform and an information source. Conclusions Although individual-focused literature tends to demonstrate a positive impact of the internet on trust in doctors in China, our study, which focuses on the general public, reveals contrasting results. Our findings imply that the primary manner in which internet usage, encompassing social media usage, influences public trust in doctors is by molding a collective perception of them. Consequently, the medical community may need to take a more proactive approach in expanding online communication channels for interacting with patients and the wider public.

Abstract RNA Polymerase (RNAP) II transcription on non-coding repetitive satellite DNAs plays an important role in chromosome segregation, but a little is known about the regulation of satellite transcription. We here show that Topoisomerase I (TopI), not TopII, promotes the transcription of α-satellite DNAs, the main type of satellite DNAs on human centromeres. Mechanistically, TopI localizes to centromeres, binds RNAP II and facilitates RNAP II elongation. Interestingly, in response to DNA double-stranded breaks (DSBs), α-satellite transcription is dramatically stimulated in a DNA damage checkpoint-independent but TopI-dependent manner, and these DSB-induced α-satellite RNAs form into strong speckles in the nucleus. Remarkably, TopI-dependent satellite transcription also exists in mouse 3T3 and Drosophila S2 cells and in Drosophila larval imaginal wing discs and tumor tissues. Altogether, our findings herein reveal an evolutionally conserved mechanism with TopI as a key player for the regulation of satellite transcription at both cellular and animal levels.

Automatically and accurately identifying the deformation zone of coastal slope landslides is crucial for exploring the mechanism of landslides and predicting landslide disasters. To this end, this study proposes an integrated automatic recognition method combining Image Clipping (IC), Image Information Enhancement (IE), Adaptive K-means Clustering Segmentation (AKS), and Optimization (O): IC-IE-AKS-O, which achieves precise extraction of the deformation area in coastal slope landslide images. Firstly, due to the more complex natural environment of field slopes, to extend the monitoring duration, we introduce a hierarchical operation algorithm based on the HSV color model, which effectively mitigates the impact of sunlight, rain, and foggy weather on image recognition accuracy. Secondly, this study proposes a 2D landslide image segmentation technique that combines K-means clustering with global threshold segmentation for landslide images, enabling the segmentation of small image regions with precision. Finally, we combine image information enhancement technology with image segmentation technology. To verify its effectiveness, we identify a landslide image of a coastal slope in Pingtan. The method displays an average relative error of 5.20% and 5.14% in the X and Y directions, respectively. Its advantages are threefold: (1) The combination of image information enhancement and segmentation techniques can more accurately identify landslide areas that appear blurred in the image; (2) expanding the temporal dimension of coastal slope monitoring; (3) providing excellent boundary conditions and segmentation results. The practical application of this method ensures the stable and accurate operation of the coastal slope monitoring system, providing a safeguard for the sustainable development of marine safety.

Abstract Cervical cancer is a significant global health issue, its prevalence and prognosis highlighting the importance of early screening for effective prevention. This research aimed to create and validate an artificial intelligence cervical cancer screening (AICCS) system for grading cervical cytology. The AICCS system was trained and validated using various datasets, including retrospective, prospective, and randomized observational trial data, involving a total of 16,056 participants. It utilized two artificial intelligence (AI) models: one for detecting cells at the patch-level and another for classifying whole-slide image (WSIs). The AICCS consistently showed high accuracy in predicting cytology grades across different datasets. In the prospective assessment, it achieved an area under curve (AUC) of 0.947, a sensitivity of 0.946, a specificity of 0.890, and an accuracy of 0.892. Remarkably, the randomized observational trial revealed that the AICCS-assisted cytopathologists had a significantly higher AUC, specificity, and accuracy than cytopathologists alone, with a notable 13.3% enhancement in sensitivity. Thus, AICCS holds promise as an additional tool for accurate and efficient cervical cancer screening.

From geometric point of view, we introduced the Sombor-Wiener index of a graph and studied the basic properties of the new index. It was shown that the Sombor-Wiener index was useful in predicting the acentric factor of octane isomers. In addition, we proposed a degree-weighted Wiener index to generalize the Schultz index, the Gutman index, and the Sombor-Wiener index. Meanwhile, we gave the calculation formula of degree-weighted Wiener index for generalized Bethe trees.

Abstract DNA methylation is an important part of the genomic biology, which recently allowed the identification of key biomarkers for a variety of cancers, including cutaneous melanoma. Despite the current knowledge in cutaneous melanoma, there is a clear need for new efficient biomarkers in clinical application of detection. We use The Cancer Genome Atlas data as a training set and a multi-stage screening strategy to identify prognostic characteristics of melanoma based on DNA methylation. Three DNA methylation CpG sites were identified to be related to the overall survival in the skin cutaneous melanoma cohort. This signature was validated in two independent datasets from Gene Expression Omnibus. The stratified analysis by clinical stage, age, gender, and grade retained the statistical significance. The methylation signature was significantly correlated with immune cells and anti-tumor immune response. Moreover, gene expression corresponding to the candidate CpG locus was also significantly correlated with the survival rate of the patient. About 49% of the prognostic effects of methylation are mediated by affecting the expression of the corresponding genes. The prognostic characteristics of DNA methylation combined with clinical information provide a better prediction value tool for melanoma patients than the clinical information alone. However, more experiments are required to validate these findings. Overall, this signature presents a prospect of novel and wide-ranging applications for appropriate clinical adjuvant trails.

Abstract Background Hair follicle stem cells (HFSCs) typically remain quiescent and are activated only during the transition from telogen to anagen to ensure that the hair follicle enters a new cycle. The metabolic behavior of stem cells in tissues is regulated by macroautophagy/autophagy, and changes in HFSC metabolism directly affect their activation and maintenance. However, the role of autophagy in the regulation of HFSC metabolism and function remains unclear. Methods Back skin samples were obtained from mice at different hair follicle cycle stages, and immunofluorescence staining was used to monitor autophagy in HFSCs. Mouse and human hair follicles were treated with rapamycin (Rapa, an autophagy activator) or 3-methyladenine (3-MA, an autophagy inhibitor). The effects of autophagy on the hair follicle cycle and HFSC were investigated by imaging, cell proliferation staining, and HFSC-specific marker staining. The influence and mechanism of autophagy on HFSC metabolism were explored using RNA sequencing, real-time polymerase chain reaction, immunohistochemical staining, and detection of lactate and glucose concentrations. Finally, the influence of autophagy-induced glycolysis on HFSC and the hair follicle cycle was verified by stem cell characteristics and in vivo functional experiments. Results Autophagy in HFSC was highest during the transition from telogen to anagen. Inhibiting autophagy with 3-MA led to early entry into catagen and prolonged telogen, whereas Rapa promoted autophagy and hair growth. Autophagy activated HFSC by increasing the expression and activity of HFSC lactate dehydrogenase (Ldha), thereby transforming HFSC metabolism into glycolysis. Inhibition of Ldha expression counteracted the effects of autophagy. Conclusions Autophagy activated HFSC by promoting the transition from HFSC metabolism to glycolysis, ultimately initiating the hair follicle cycle and promoting hair growth. Graphical Abstract

Let $G$ be a simple undirected graph with vertex set $V(G)=\{v_1, v_2,\ldots,v_n\}$ and edge set $E(G)$. The Sombor matrix $\mathcal{S}(G)$ of a graph $G$ is defined so that its $(i,j)$-entry is equal to $\sqrt{d_i^2+d_j^2}$ if the vertices $v_i$ and $v_j$ are adjacent, and zero otherwise, where $d_i$ denotes the degree of vertex $v_i$ in $G$. In this paper, lower and upper bounds on the spectral radius, energy and Estrada index of the Sombor matrix of graphs are obtained, and the respective extremal graphs are characterized.

Summary: Background: The pathological examination of lymph node metastasis (LNM) is crucial for treating prostate cancer (PCa). However, the limitations with naked-eye detection and pathologist workload contribute to a high missed-diagnosis rate for nodal micrometastasis. We aimed to develop an artificial intelligence (AI)-based, time-efficient, and high-precision PCa LNM detector (ProCaLNMD) and evaluate its clinical application value. Methods: In this multicentre, retrospective, diagnostic study, consecutive patients with PCa who underwent radical prostatectomy and pelvic lymph node dissection at five centres between Sep 2, 2013 and Apr 28, 2023 were included, and histopathological slides of resected lymph nodes were collected and digitised as whole-slide images for model development and validation. ProCaLNMD was trained at a dataset from a single centre (the Sun Yat-sen Memorial Hospital of Sun Yat-sen University [SYSMH]), and externally validated in the other four centres. A bladder cancer dataset from SYSMH was used to further validate ProCaLNMD, and an additional validation (human-AI comparison and collaboration study) containing consecutive patients with PCa from SYSMH was implemented to evaluate the application value of integrating ProCaLNMD into the clinical workflow. The primary endpoint was the area under the receiver operating characteristic curve (AUROC) of ProCaLNMD. In addition, the performance measures for pathologists with ProCaLNMD assistance was also assessed. Findings: In total, 8225 slides from 1297 patients with PCa were collected and digitised. Overall, 8158 slides (18,761 lymph nodes) from 1297 patients with PCa (median age 68 years [interquartile range 64–73]; 331 [26%] with LNM) were used to train and validate ProCaLNMD. The AUROC of ProCaLNMD ranged from 0.975 (95% confidence interval 0.953–0.998) to 0.992 (0.982–1.000) in the training and validation datasets, with sensitivities > 0.955 and specificities > 0.921. ProCaLNMD also demonstrated an AUROC of 0.979 in the cross-cancer dataset. ProCaLNMD use triggered true reclassification in 43 (4.3%) slides in which micrometastatic tumour regions were initially missed by pathologists, thereby correcting 28 (8.5%) missed-diagnosed cases of previous routine pathological reports. In the human-AI comparison and collaboration study, the sensitivity of ProCaLNMD (0.983 [0.908–1.000]) surpassed that of two junior pathologists (0.862 [0.746–0.939], P = 0.023; 0.879 [0.767–0.950], P = 0.041) by 10–12% and showed no difference to that of two senior pathologists (both 0.983 [0.908–1.000], both P > 0.99). Furthermore, ProCaLNMD significantly boosted the diagnostic sensitivity of two junior pathologists (both P = 0.041) to the level of senior pathologists (both P > 0.99), and substantially reduced the four pathologists’ slide reviewing time (−31%, P

Sargassum fusiforme is rich in a variety of nutrients and active substances, and is one of the important economic seaweeds in China. Its quality could be easily affected by environmental factors such as marine areas. To figure out the differences in nutritional composition of Sargassum fusiforme cultivated in different marine areas, this paper used Sargassum fusiforme cultivated in seven marine areas in Zhejiang Province as the research object, and determined the basic nutrients, amino acids and fatty acids using the National Food Safety Standard. The antioxidant activities of the seven Sargassum fusiforme polysaccharides were determined using DPPH· and ·OH scavenging as evaluation criteria, and the structural composition of seven kinds of Sargassum fusiforme polysaccharides were preliminarily analyzed. The results showed that, the moisture content of seven Sargassum fusiforme was highest, between (82.50±0.32) and (86.50±0.23) g/100 g. In addition to moisture content, the other main nutrient component was polysaccharide. The polysaccharide content of Sargassum fusiforme cultivated in No.7 marine area was the highest (P

The mud crab Scylla paramamosain is a key species in China due to its high nutritional value and great economic worth and has grown in popularity. Myo-inositol can modulate versatile physiological functions in aquatic animals. In the present study, S. paramamosain megalopa were given graded concentrations of myo-inositol (0, 1, 2, 4, and 8 ppm) by water immersion to explore how their metamorphosis would be affected. The results showed that supplementing with myo-inositol remarkably increased transformation and survival rate from megalopa to crablet by at least 1.16 and 1.26 times, respectively. To decipher the molecular mechanism of how myo-inositol increases metamorphosis and survival rate, we further performed transcriptome-based gene expression profiling of both megalopa and crablet treated with myo-inositol. The integrative transcriptome analyses predicted that the differentially expressed genes (DEGs) were significantly enriched in chitinase activity, structural constituent of cuticle, and chitin binding, which are associated with the decomposition and reconstruction of cuticle. qPCR results confirmed that myo-inositol mediated gene expression levels of the above cuticle-related pathways. Considering the importance of the cuticle in exoskeleton formation and molting, it can be concluded that myo-inositol-induced changes in the cuticle decomposition and reconstruction might have accelerated the transformation from megalopa to crablet of S. paramamosain. Besides, numerous DEGs were significantly enriched in protein digestion and absorption, amino sugar and nucleotide sugar metabolism. It implies that myo-inositol may improve survival by regulating energy or nutrient absorption. Additionally, the accelerated metamorphosis by myo-inositol may improve survival from megalopa to crablet of S. paramamosain. Overall, this study will provide the first insights into the underlying molecular mechanisms by which myo-inositol increases metamorphosis and survival.

Introduction: The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics. Objectives: Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process. Methods: In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry. Results: R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage. Conclusion: The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis.

Lung tumor-promoting environmental exposures and γherpesvirus infections are associated with Type 17 inflammation. To test the effect of γherpesvirus infection in promoting lung tumorigenesis, we infected mutant K-Ras-expressing (K-RasLA1) mice with the murine γherpesvirus MHV68 via oropharyngeal aspiration. After 7 weeks, the infected mice displayed a more than 2-fold increase in lung tumors relative to their K-RasLA1 uninfected littermates. Assessment of cytokines in the lung revealed that expression of Type 17 cytokines (Il-6, Cxcl1, Csf3) peaked at day 7 post-infection. These observations correlated with the post-infection appearance of known immune mediators of tumor promotion via IL-17A in the lungs of tumor-bearing mice. Surprisingly, Cd84, an immune cell marker mRNA, did not increase in MHV68-infected wild-type mice lacking lung tumors. Csf3 and Cxcl1 protein levels increased more in the lungs of infected K-RasLA1 mice relative to infected wild-type littermates. Flow cytometric and transcriptomic analyses indicated that the infected K-RasLA1 mice had increased Ly6Gdim/Ly6Chi immune cells in the lung relative to levels seen in uninfected control K-RasLA1 mice. Selective methylation of adenosines (m6A modification) in immune-cell-enriched mRNAs appeared to correlate with inflammatory infiltrates in the lung. These observations implicate γherpesvirus infection in lung tumor promotion and selective accumulation of immune cells in the lung that appears to be associated with m6A modification of mRNAs in those cells.

Coastal concrete structures, such as cross-sea bridges and tunnels, are susceptible to the penetration of chloride ions, which can lead to the deterioration of the passive film on the rebar surface, consequently accelerating the corrosion process. Conventional methods for monitoring chloride ions typically require in situ drilling for sample collection, thereby compromising efficiency and accuracy. Additionally, real-time monitoring and early warning cannot be achieved. To address these challenges, this work introduces a fluorescent-probe-based fiber optic sensor for monitoring chloride levels in concrete structures. Quinine sulfate was chosen as the fluorescent material due to its exceptional sensitivity to chloride ions and its stability in concrete environments. The proposed sensor was manufactured using sol–gel and 3D-printing techniques. Tests were conducted using concrete simulation fluid and cement mortar specimens. The results demonstrate that the sensitivity of the proposed sensor is greater than 0.01 M, and its accuracy in penetration depth measurement is better than 3 mm. The findings confirm that the designed fiber optic sensor based on quinine sulfate enables real-time monitoring of chloride ions in concrete structures, offering high sensitivity (0.1% in concentration and 2.7 mm in terms of penetration depth), unique selectivity (as it is immune to other ions whose concentrations are 10 times higher than those of Cl−), and a compact size (10 × 20 mm). These attributes render it promising for practical engineering applications.

Abstract Background Peripheral intravenous catheters (PIVCs) are the most used invasive medical device in healthcare. Yet around half of insertion attempts are unsuccessful leading to delayed medical treatments and patient discomfort of harm. Ultrasound-guided PIVC (USGPIVC) insertion is an evidence-based intervention shown to improve insertion success especially in patients with Difficult IntraVenous Access (BMC Health Serv Res 22:220, 2022), however the implementation in some healthcare settings remains suboptimal. This study aims to co-design interventions that optimise ultrasound guided PIVC insertion in patients with DIVA, implement and evaluate these initiatives and develop scale up activities. Methods A stepped-wedge cluster randomized controlled trial will be conducted in three hospitals (two adult, one paediatric) in Queensland, Australia. The intervention will be rolled out across 12 distinct clusters (four per hospital). Intervention development will be guided by Michie’s Behavior Change Wheel with the aim to increase local staff capability, opportunity, and motivation for appropriate, sustainable adoption of USGPIVC insertion. Eligible clusters include all wards or departments where > 10 PIVCs/week are typically inserted. All clusters will commence in the control (baseline) phase, then, one cluster per hospital will step up every two months, as feasible, to the implementation phase, where the intervention will be rolled out. Implementation strategies are tailored for each hospital by local investigators and advisory groups, through context assessments, staff surveys, and stakeholder interviews and informed by extensive consumer interviews and consultation. Outcome measures align with the RE-AIM framework including clinical-effectiveness outcomes (e.g., first-time PIVC insertion success for DIVA patients [primary outcome], number of insertion attempts); implementation outcomes (e.g., intervention fidelity, readiness assessment) and cost effectiveness outcomes. The Consolidated Framework for Implementation Research framework will be used to report the intervention as it was implemented; how people participated in and responded to the intervention; contextual influences and how the theory underpinning the intervention was realised and delivered at each site. A sustainability assessment will be undertaken at three- and six-months post intervention. Discussion Study findings will help define systematic solutions to implement DIVA identification and escalation tools aiming to address consumer dissatisfaction with current PIVC insertion practices. Such actionable knowledge is critical for implementation of scale-up activities. Trial registration Prospectively registered (Australian and New Zealand Clinical Trials Registry; ACTRN12621001497897).

Abstract 2D transition metal carbides and nitrides (MXenes) suggest an uncommonly broad combination of important functionalities amongst 2D materials. Nevertheless, MXene suffers from facile oxidation and colloidal instability upon conventional water‐based processing, thus limiting applicability. By experiments and theory, It is suggested that for stability and dispersibility, it is critical to select uncommonly high permittivity solvents such as N‐methylformamide (NMF) and formamide (FA) (εr = 171, 109), unlike the classical solvents characterized by high dipole moment and polarity index. They also allow high MXene stacking order within thin films on carbon nanotube (CNT) substrates, showing very high Terahertz (THz) shielding effectiveness (SE) of 40–60 dB at 0.3–1.6 THz in spite of the film thinness

Currently, the use of nanotechnology to repurpose traditional drugs has emerged as a promising strategy for cancer treatment. Quercetin (Qu), a chemotherapy molecule, has excellent antitumor activity, and IR780, a photosensitizer, possesses sound tumor phototherapy effects. However, both compounds have poor water solubility and other drawbacks that hinder their extensive clinical applications. To effectively utilize two molecules in the fight against cancer, a new multifunctional chemical-phototherapy nanoplatform with tumor target and glutathione (GSH) response was designed. By modifying hyaluronic acid (HA), the amphiphilic molecule carrying biotin and IR780 was obtained, which self-assembled to load the antitumor active molecule Qu, namely Qu@BHSI. In addition to addressing the hydrophobic issue of Qu and IR780, the prepared nanoparticles can rapidly release Qu with high concentrations of GSH present and generate heat and cytotoxic reactive oxygen species (ROS) under near-infrared light. The biological function research showed that Qu@BHSI nanoparticles had the ability to suppress the growth of A549 cells, induce cell apoptosis, stimulate ROS production in zebrafish, and inhibit angiogenesis in transgenic zebrafish. The construction of nanosystems provides new or alternative strategies and approaches for effectively repurposing classical drug molecules including photosensitizers and chemotherapy drugs.

Summary: The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR’s canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer.

Abstract The Li metal is an ideal anode material owing to its high theoretical specific capacity and low electrode potential. However, its high reactivity and dendritic growth in carbonate-based electrolytes limit its application. To address these issues, we propose a novel surface modification technique using heptafluorobutyric acid. In-situ spontaneous reaction between Li and the organic acid generates a lithiophilic interface of lithium heptafluorobutyrate for dendrite-free uniform Li deposition, which significantly improves the cycle stability (Li/Li symmetric cells >1200 h at 1.0 mA cm−2) and Coulombic efficiency (>99.3%) in conventional carbonate-based electrolytes. This lithiophilic interface also enables full batteries to achieve 83.2% capacity retention over 300 cycles under realistic testing condition. Lithium heptafluorobutyrate interface acts as an electrical bridge for uniform lithium-ion flux between Li anode and plating Li, which minimizes the occurrence of tortuous lithium dendrites and lowers interface impedance.

Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, through simultaneously inhibiting Myc and HIF1α expression. Echinomycin treatment also induces viral lytic gene expression whereas not increasing infectious virions production from KSHV + tumor cells. Our comparative transcriptomic analysis has identified a bunch of new Echinomycin-regulated, Myc- and HIF1α-related genes contributed to KSHV pathogenesis, including KDM4B and Tau, which are required for the survival of KSHV + tumor cells with functional validation. These data together reveal that dual targeting Myc and HIF1α such as using Echinomycin may represent a new and promising option for treatments of these virus-associated malignancies.

Evaptotranspiration (ETc) is a crucial link in the farmland water cycle process. To accurately obtain the citrus ETc in different slope positions, the METRIC, RSEB, and FAO Penman–Monteith (P-M) models were constructed based on unmanned aerial vehicle (UAV) multispectral images to invert the ETc values. The ETc of citrus calculated by the P-M model was used as a reference standard, and the accuracy of the ETc inversion was evaluated by the METRIC model and the RSEB model. The results showed that the R2, RMSE, and SE of the METRIC model and the RSEB model were 0.396 and 0.486, 4.940 and 3.010, and 4.570 and 2.090, respectively, indicating a higher accuracy of the RSEB model for inverting the ETc values. Furthermore, the accuracy of the RSEB model could be improved by introducing the optimal correction coefficient (after correction: RMSE = 1.470, SE = 0.003). Based on the modified RSEB model, the ETc values of the citrus in different slope positions were obtained. We also found that the middle slope ETc > the top slope ETc > the bottom slope ETc, indicating that the slope position indeed affected the citrus ETc. This research provides a favorable framework for the ETc inversion, and the results are of theoretical and practical importance to realize crop water conservation.

Recent studies have shown that chlorogenic acid (CGA), which is present in coffee, has protective effects on the nervous system. However, its role in neonatal hypoxic-ischemic brain injury remains unclear. In this study, we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA. We found that CGA intervention effectively reduced the volume of cerebral infarct, alleviated cerebral edema, restored brain tissue structure after injury, and promoted axon growth in injured brain tissue. Moreover, CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival. In addition, changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA. Furthermore, CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2. In summary, our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis, providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Abstract Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p

Abstract A growing body of evidence has indicated an expanding functional network of B‐cell lymphoma 2 (BCL‐2) family proteins beyond regulation of cell death and survival. Here, we examined the role and mechanisms of BH3 interacting‐domain death agonist (BID), a pro‐death BCL‐2 family member, in the development of diet‐induced metabolic dysfunction. Mice deficient in bid (bid−/−) were resistant to high‐fat diet (HFD)–induced obesity, hepatic steatosis, and dyslipidemia with an increased insulin sensitivity. Indirect calorimetry analysis indicated that bid deficiency increased metabolic rate and decreased respiratory exchange ratio, suggesting a larger contribution of lipids to overall energy expenditure. While expression of several genes related to lipid accumulation was only increased in wild‐type livers, metabolomics analysis revealed a consistent reduction in fatty acids but an increase in certain sugars and Krebs cycle intermediates in bid−/− livers. Gut microbiota (GM) analysis indicated that HFD induced gut dysbiosis with differential patterns in wild‐type and in bid−/− mice. Notably, abrogation of GM by antibiotics during HFD feeding eliminated the beneficial effects against obesity and hepatic steatosis conferred by the bid deficiency. Conclusion: These results indicate that the protective role of bid‐deficiency against diet‐induced metabolic dysfunction interacts with the function of GM.

Let $ A(G) $ and $ D(G) $ be the adjacency matrix and the degree diagonal matrix of a graph $ G $, respectively. For any real number $ \alpha \in[0, 1] $, Nikiforov defined the $ A_{\alpha} $-matrix of a graph $ G $ as $ A_{\alpha}(G) = \alpha D(G)+(1-\alpha)A(G) $. Let $ S_k(A_{\alpha}(G)) $ be the sum of the $ k $ largest eigenvalues of $ A_{\alpha}(G) $. In this paper, some bounds on $ S_k(A_{\alpha}(G)) $ are obtained, which not only extends the results of the sum of the $ k $ largest eigenvalues of the adjacency matrix and signless Laplacian matrix, but it also gives new bounds on graph energy.

Let $ A(G) $ and $ D(G) $ be the adjacency matrix and the degree diagonal matrix of a graph $ G $, respectively. For any real number $ \alpha \in[0, 1] $, Nikiforov recently defined the $ A_{\alpha} $-matrix of $ G $ as $ A_{\alpha}(G) = \alpha D(G)+(1-\alpha)A(G) $. The graph invariant $ S_{\alpha}^{p}(G) $ is the sum of the $ p $-th power of the $ A_{\alpha} $-eigenvalues of $ G $ for $ \frac{1}{2} < \alpha < 1 $, which has a close relation to the $ \alpha $-Estrada index. In this paper, we establish some bounds on $ S_{\alpha}^{p}(G) $ and characterize the extremal graphs. In particular, we present some bounds on $ S_{\alpha}^{p}(G) $ in terms of the degree sequences, order and size of $ G $ by using majorization techniques. Moreover, we give lower and upper bounds for $ S_{\alpha}^{p}(G) $ of a bipartite graph and characterize the extremal graphs.

IntroductionThe traditional spraying system is not suitable for agricultural plant protection in small plots due to its disadvantages of weak droplet refining ability, small spraying area, large pesticide consumption, and high manual spraying cost. At present, spraying pesticide is the main way to resist crop diseases and insect pests. The utilization rate of pesticide is only 38.8% in China, which leads to serious waste and serious environmental pollution. It is necessary to develop advanced plant protection equipment and pesticide application technology to solve the problem. The combination of agricultural plant protection vehicle and electrostatic spray technology may solve the problems of spraying efficiency, droplet adsorption rate and evenness. It is of great significance to improve the efficiency of plant protection and pesticide utilization.MethodsIn this paper, the principle of droplet charging is described, an electrostatic spraying system is designed and tested, and the effects of charging voltage and pump pressure on the droplet charge ratio and droplet size are analyzed.Results and discussionThis study has shown that electrostatic spraying systems are suitable for agricultural plant protection unmanned vehicles.

Corn straw biochar was used as a carrier to immobilize white rot fungi and the removal performance of immobilized pellets for acid red G (ARG) dye was studied. The results showed that the removal rate of ARG could reach 96.17% under the best preparation conditions of immobilized pellets (3% sodium alginate concentration, 0.7% corn straw biochar, 5% white rot fungus mycelium suspension, 4% CaCl2, and 36 h immobilization time). The orthogonal test results showed that the best combination was the immobilized pellets dosage of 200/100 mL, pH of 4.5, rotation speed of 150 r/min, and initial concentration of 20 mg/L dye at 30 °C. The degradation pathway of ARG by immobilized microspheres was studied by ultraviolet-visible spectrometer, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometry. The results showed that ARG was degraded into aniline and 5-(acetamino)-4-hydroxy-3-amino-2,7-naphthalene disulfonic acid. Aniline was further deaminated to form benzene, and benzene was ring opened to form other organic compounds; 5-(acetylamino)-4-hydroxy-3-amino-2,7-naphthalene disulfonic acid was dehydroxylated to form 5-(acetylamino)-3-amino-2,7-naphthalene disulfonic acid. This study shows that the prepared biochar immobilized pellets can be used as an efficient water treatment material to remove ARG dye from wastewater. HIGHLIGHTS The use of biochar as a fungal fixation material not only saved energy, provided an effective solution for the disposal of agricultural waste and conformed to China's concept of waste treatment, but also provided a theoretical research basis for biochar as a fungal fixation material.; The combination of biochar and other materials provided a theoretical basis for the compound fixation fungus treatment dye wastewater.;

Abstract Background Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of estrogen receptor, progesterone receptor, and HER2. Our lab previously characterized miR-3189-3p as a microRNA with potent anti-cancer activity against glioblastoma. Here, we hypothesized a similar activity in TNBC cells. As miR-3189-3p is predicted to target a variety of RNA binding proteins, we further hypothesized an inhibitory effect of this miRNA on protein synthesis. Methods MDA-MB-231 and MDA-MB-468 cells were used to investigate the effect of miR-3189-3p on cell proliferation, migration, and invasion. TGCA database was used to analyze the expression of miR-3189-3p, c-MYC, 4EPB1, and eIF4E in breast cancer. Western blotting and RT-qPCR assays were used to assess the expression of selected proteins and RNAs after transfections. Results Although c-MYC is not a predicted gene target for miR-3189-3p, we discovered that c-MYC protein is downregulated in miRNA-treated TNBC cells. We found that the downregulation of c-MYC by miR-3189-3p occurs in both normal growth conditions and in the absence of serum. The mechanism involved the direct inhibition of eIF4EBP1 by miR-3189-3p. Additionally, we found that miR-3189-3p could negatively affect cap-independent translation mediated by internal ribosome entry sites (IRES) or by m6A. Finally, miR-3189-3p sensitized TNBC cells to doxorubicin. Conclusion Overall, results indicated that miR-3189-3p exerts its anti-tumor activity through targeting translational regulatory proteins leading to an impairment in c-MYC translation, and possibly other oncogenic factors, suggesting that miR-3189-3p, alone or in combination, could be a valuable therapeutic approach against a malignancy with few treatment options.

Concrete is the most commonly used construction material nowadays. With emerging cutting-edge technologies such as nanomaterials (graphene, carbon nanotubes, etc.), advanced sensing (fiber optics, computer tomography, etc.), and artificial intelligence, concrete can now achieve self-sensing, self-healing, and ultrahigh performance. The concept and functions of smart concrete have thus been partially realized. However, due to the wider application location (coastal areas, cold regions, offshore, and deep ocean scenarios) and changing climate (temperature increase, more CO2 emissions, higher moisture, etc.), durability monitoring (pH, ion penetration, carbonation, corrosion, etc.) becomes an essential component for smart concrete. Fiber optic sensors (FOS) have been widely explored in recent years for concrete durability monitoring due to their advantages of high sensitivity, immunity to harsh environments, small size, and superior sensitivity. The purpose of this review is to summarize FOS development and its application in concrete durability monitoring in recent years. The objectives of this study are to (1) introduce the working principle of FOS, including fiber Bragg grating (FBG), long-period fiber grating (LPFG), surface plasmon resonance (SPR), fluorescence-based sensors, and distributed fiber optic sensors (DFOS); (2) compare the sensitivity, resolution, and application scenarios of each sensor; and (3) discuss the advantages and disadvantages of FOS in concrete durability monitoring. This review is expected to promote technical development and provide potential research paths in the future for FOS in durability monitoring in smart concrete.

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. Here, the authors show that also presynaptic NMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner.

Abstract In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and high-throughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in mice. Mechanistically, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B cells. The stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and osteoclastogenesis. Induction of HSP70 expression by geranylgeranylacetone (GGA) administration alleviates ovariectomy-induced osteoporosis. Moreover, RANKL gene expression has a positive correlation with HIF1A expression in human B cells. In conclusion, HIF-1α signaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.

We introduce the general Albertson irregularity index of a connected graph $ G $ and define it as $ A_{p}(G) = (\sum_{uv\in E(G)}|d(u)-d(v)|^p)^{\frac{1}{p}} $, where $ p $ is a positive real number and $ d(v) $ is the degree of the vertex $ v $ in $ G $. The new index is not only generalization of the well-known Albertson irregularity index and $ \sigma $-index, but also it is the Minkowski norm of the degree of vertex. We present lower and upper bounds on the general Albertson irregularity index. In addition, we study the extremal value on the general Albertson irregularity index for trees of given order. Finally, we give the calculation formula of the general Albertson index of generalized Bethe trees and Kragujevac trees.

Let $ G $ be a simple connected graph with the vertex set $ V(G) $ and $ d_{B}(u, v) $ be the biharmonic distance between two vertices $ u $ and $ v $ in $ G $. The biharmonic index $ BH(G) $ of $ G $ is defined as $ BH(G) = \frac{1}{2}\sum\limits_{u\in V(G)}\sum\limits_{v\in V(G)}d_{B}^2(u, v) = n\sum\limits_{i = 2}^{n}\frac{1}{\lambda_i^2(G)}, $ where $ \lambda_i(G) $ is the $ i $-th eigenvalue of the Laplacian matrix of $ G $ with $ n $ vertices. In this paper, we provide the mathematical relationships between the biharmonic index and some classic topological indices: the first Zagreb index, the forgotten topological index and the Kirchhoff index. In addition, the extremal value on the biharmonic index for all graphs with diameter two, trees and firefly graphs are given, respectively. Finally, some graph operations on the biharmonic index are presented.

Akebia quinata is a traditional medicinal plant distributed in East Asia and its fruits are applicated in food and pharmaceutical fields. Herein, a novel polysaccharide (AQP70-2A) with a molecular weight of 1.49 × 104 Da was isolated from the fruits of A. quinata. Results of the chemical and spectroscopic analysis indicated that AQP70-2A was an arabinofuranan with a backbone mainly consisting of → 5)-α-l-Araf-(1→, →3,5)-α-l-Araf-(1→, and → 2,3,5)-α-l-Araf-(1→, and it also contained two types of branch chains. At the cellular level, AQP70-2A did not show significant antitumor properties, while selenylation significantly made the inhibitory effect of this natural macromolecule on HepG2 cells to be increased. Furthermore, the zebrafish xenograft model confirmed that selenized polysaccharide Se-AQP70-2A effectively blocked hepatocellular carcinoma cells invasion and metastasis. Meanwhile, the inhibition of Se-AQP70-2A on development of intersegmental vessels revealed its antiangiogenic activity.

Primary effusion lymphoma (PEL) caused by Kaposi sarcoma-associated herpesvirus (KSHV) is an aggressive malignancy with poor prognosis even under chemotherapy. Currently, there is no specific treatment for PEL therefore requiring new therapies. Both histone deacetylases (HDACs) and bromodomain-containing protein 4 (BRD4) have been found as therapeutic targets for PEL through inducing viral lytic reactivation. However, the strategy of dual targeting with one agent and potential synergistic effects have never been explored. In the current study, we first demonstrated the synergistic effect of concurrently targeting HDACs and BRD4 on KSHV reactivation by using SAHA or entinostat (HDACs inhibitors) and (+)-JQ1 (BRD4 inhibitor), which indicated dual blockage of HDACs/BRD4 is a viable therapeutic approach. We were then able to rationally design and synthesize a series of new small-molecule inhibitors targeting HDACs and BRD4 with a balanced activity profile by generating a hybrid of the key binding motifs between (+)-JQ1 and entinostat or SAHA. Upon two iterative screenings of optimized compounds, a pair of epimers, 009P1 and 009P2, were identified to better inhibit the growth of KSHV positive lymphomas compared to (+)-JQ1 or SAHA alone at low nanomolar concentrations, but not KSHV negative control cells or normal cells. Mechanistic studies of 009P1 and 009P2 demonstrated significantly enhanced viral reactivation, cell cycle arrest and apoptosis in KSHV+ lymphomas through dually targeting HDACs and BRD4 signaling activities. Importantly, in vivo preclinical studies showed that 009P1 and 009P2 dramatically suppressed KSHV+ lymphoma progression with oral bioavailability and minimal visible toxicity. These data together provide a novel strategy for the development of agents for inducing lytic activation-based therapies against these viruses-associated malignancies.

BackgroundThis study explored the effectiveness of pre-operative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS).MethodsPatients (n = 708) were randomized into two groups. The butorphanol group (Group B, n = 358) received butorphanol infusion (20 ug/kg) before anesthesia induction, while the control group (Group C, n = 350) received an equal volume of normal saline infusion. General anesthesia was induced with sufentanil, propofol, and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the hemodynamic indices within 20% of the baseline.ResultsThe incidence of EA was significantly lower in Group B than that in Group C (Group B vs. C: 24.3% vs. 31.4%, respectively; P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012), and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B.ConclusionPre-operative intravenous injection of butorphanol decreased the incidence of EA after FESS and provided smooth and hemodynamically stable emergence without extending the stay in post-anesthesia care unit.Clinical trial registrationhttps://www.clinicaltrials.gov/, identifier NCT03398759.

The southern part of the Kyushu-Palau Ridge (KPR) is located at the conjunction of the West Philippine Basin, the Parece Vela Basin, the Palau Basin, and the Caroline Basin. This area has extremely complex structures and is critical for the research on the tectonic evolution of marginal seas in the Western Pacific Ocean. However, only few studies have been completed on the southern part, and the geophysical fields and deep structures in this part are not well understood. Given this, this study finely depicts the characteristics of the gravity and magnetic anomalies and extracts information on deep structures in the southern part of the KPR based on the gravity and magnetic data obtained from the 11th expedition of the deep-sea geological survey of the Western Pacific Ocean conducted by the Guangzhou Marine Geological Survey, China Geological Survey using the R/V Haiyangdizhi 6. Furthermore, with the data collected on the water depth, sediment thickness, and multichannel seismic transects as constraints, a 3D density model and Moho depths of the study area were obtained using 3D density inversion. The results are as follows. (1) The gravity and magnetic anomalies in the study area show distinct zoning and segmentation. In detail, the gravity and magnetic anomalies to the south of 11°N of the KPR transition from high-amplitude continuous linear positive anomalies into low-amplitude intermittent linear positive anomalies. In contrast, the gravity and magnetic anomalies to the north of 11°N of the KPR are discontinuous and show alternating positive and negative anomalies. These anomalies can be divided into four sections, of which the separation points correspond well to the locations of deep faults, thus, revealing different field-source attributes and tectonic genesis of the KPR. (2) The Moho depth in the basins in the study area is 6–12 km. The Moho depth in the southern part of KPR show segmentation. Specifically, the depth is 10–12 km to the north of 11°N, 12–14 km from 9.5°N to 11°N, 14–16 km from 8.5°N to 9.5°N, and 16–25 km in the Palau Islands. (3) The KPR is a remnant intra-oceanic arc with the oceanic-crust basement.which shows noticeably discontinuous from north to south in geological structure and is intersected by NEE-trending lithospheric-scale deep faults. With large and deep faults F3 and F1 (the Mindanao fault) as boundaries overall, the southern part of the KPR can be divided into three zones. In detail, the portion to the south of 8.5°N (F3) is a tectonically active zone, the KPR portion between 8.5°N and 11°N is a tectonically active transition zone, and the portion to the north of 11°N is a tectonically inactive zone. (4) The oceanic crust in the KPR is slightly thicker than that in the basins on both sides of the ridge, and it is inferred that the KPR formed from the thickening of the oceanic crust induced by the upwelling of deep magma in the process of rifting of remnant arcs during the Middle Oligocene. In addition, it is inferred that the thick oceanic crust under the Palau Islands is related to the constant upwelling of deep magma induced by the continuous northwestward subduction of the Caroline Plate toward the Palau Trench since the Late Oligocene. This study provides a scientific basis for systematically understanding the crustal attributes, deep structures, and evolution of the KPR.©2021 China Geology Editorial Office.

Abstract Background Immune checkpoint inhibitors (ICIs) have elicited durable antitumor responses in multiple types of cancers. However, ICIs could also induce potential toxicities that involve all organs, including renal system. In this study, we aimed to conduct a comprehensive description of the ICIs‐induced renal toxicities and the potential effects of chemotherapy. Methods We conducted a pharmacovigilance study based on US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database between 01 January 2014 and 30 June 2019. Disproportionality analysis was used to assess the association between ICIs and renal adverse events (AEs), including reporting odds ratio (ROR) and information component (IC). ROR025 and IC025 are, respectively, 95% confidence interval lower end of ROR and IC. If the value of ROR025 exceeding one or IC025 higher than zero, then a signal was considered statistically significant. Results A total of 30,602,758 reports were extracted from the database, with 4578 reports for ICIs‐associated renal AEs. Renal AEs were more frequently reported in anti‐PD‐1/PD‐L1 versus anti‐CTLA‐4 monotherapy group (ROR: 1.75, 95% CI: 1.52–2.01). Similarly, renal AEs were more commonly reported in ICIs polytherapy other than monotherapy group (ROR: 1.18, 95% CI: 1.10–1.27). Notably, ICIs plus chemotherapy strategies reported more renal toxicities compared to sole ICIs regimens (ROR: 1.30, 95% CI: 1.17–1.45), whereas exhibited lower fatality outcome rates. Importantly, acute kidney injury (1139, 24.88%) and renal failure (464, 10.14%) were the top two most commonly reported ICIs‐associated renal AEs, and also observed with the top two highest level of fatality outcome rates. Conclusions A spectrum of renal AEs was detected in ICIs regimens and could be reinforced by ICIs combination. Compared to sole ICIs regimens, ICIs plus chemotherapy strategy reported more renal toxicities but lower fatality outcome rates. With the increasing popularity of ICIs especially combination strategies, it is vital important for clinicians to guarantee balance between durable clinical effects and potential renal toxicities in latest immunotherapy strategies.

Background/Aims To evaluate temporal trends of atrial fibrillation (AF) prevalence in critically ill patients who received prolonged mechanical ventilation (MV) in the United States. Methods We used the 2008 to 2014 National Inpatient Sample to compute the weighted prevalence of AF among hospitalized adult patients on prolonged MV. We used multivariable-adjusted models to evaluate the association of AF with clinical factors, in-hospital mortality, hospitalization cost, and length of stay (LOS). Results We identified 2,578,165 patients who received prolonged MV (21.27% of AF patients). The prevalence of AF increased from 14.63% in 2008 to 24.43% in 2014 (p for trend < 0.0001). Amongst different phenotypes of critically ill patients, the prevalence of AF increased in patients with severe sepsis, asthma exacerbation, congestive heart failure exacerbation, acute stroke, and cardiac arrest. Older age, male sex, white race, medicare access, higher income, urban teaching hospital setting, and Western region were associated with a higher prevalence of AF. AF in critical illness was a risk factor for in-hospital death (odds ratio, 1.13; 95% confidence interval, 1.11 to 1.15), but in-hospital mortality in critically ill patients with AF decreased from 11.6% to 8.3%. AF was linked to prolonged LOS (2%, p < 0.0001) and high hospitalization cost (4%, p < 0.0001). LOS (−1%, p < 0.0001) and hospitalization cost (−4%, p < 0.0001) decreased yearly. Conclusions The prevalence of comorbid AF is increasing, particularly in older patients. AF may lead to poorer prognosis, and high-quality intensive care is imperative for this population.

Abstract Proper follicle development is very important for the production of mature oocytes, which is essential for the maintenance of female fertility. This complex biological process requires precise gene regulation. The most abundant modification of mRNA, N 6-methyladenosine (m6A), is involved in many RNA metabolism processes, including RNA splicing, translation, stability, and degradation. Here, we report that m6A plays essential roles during oocyte and follicle development. Oocyte-specific inactivation of the key m6A methyltransferase Mettl3 with Gdf9-Cre caused DNA damage accumulation in oocytes, defective follicle development, and abnormal ovulation. Mechanistically, combined RNA-seq and m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) data from oocytes revealed, that we found METTL3 targets Itsn2 for m6A modification and then enhances its stability to influence the oocytes meiosis. Taken together, our findings highlight the crucial roles of mRNA m6A modification in follicle development and coordination of RNA stabilization during oocyte growth.

Abstract Background Xanthine dehydrogenase (XDH) is a critical enzyme involved in the oxidative metabolism of purines, pterin and aldehydes and a central component of the innate immune system. However, the prognostic value of XDH in predicting tumor-infiltrating lymphocyte abundance, the immune response, and survival in different cancers, including hepatocellular carcinoma (HCC), is still unclear. Methods XDH expression was analyzed in multiple databases, including Oncomine, the Tumor Immune Estimation Resource (TIMER), the Kaplan–Meier plotter database, the Gene Expression Profiling Interactive Analysis (GEPIA) database, and The Cancer Genome Atlas (TCGA). XDH-associated transcriptional profiles were detected with an mRNA array, and the levels of infiltrating immune cells were validated by immunohistochemistry (IHC) of HCC tissues. A predictive signature containing multiple XDH-associated immune genes was established using the Cox regression model. Results Decreased XDH mRNA expression was detected in human cancers originating from the liver, bladder, breast, colon, bile duct, kidney, and hematolymphoid system. The prognostic potential of XDH mRNA expression was also significant in certain other cancers, including HCC, breast cancer, kidney or bladder carcinoma, gastric cancer, mesothelioma, lung cancer, and ovarian cancer. In HCC, a low XDH mRNA level predicted poorer overall survival, disease-specific survival, disease-free survival, and progression-free survival. The prognostic value of XDH was independent of the clinical features of HCC patients. Indeed, XDH expression in HCC activated several immune-related pathways, including the T cell receptor, PI3K-AKT, and MAPK signaling pathways, which induced a cytotoxic immune response. Importantly, the microenvironment of XDHhigh HCC tumors contained abundant infiltrating CD8 + T cells but not exhausted T cells. A risk prediction signature based on multiple XDH-associated immune genes was revealed as an independent predictor in the TCGA liver cancer cohort. Conclusion These findings suggest that XDH is a valuable prognostic biomarker in HCC and other cancers and indicate that it may function in tumor immunology. Loss of XDH expression may be an immune evasion mechanism for HCC.

Mesenchymal–epithelial transition (MET) exon 14 skipping mutation (METex14) is a low-frequency driver mutation in metastatic non-small cell lung cancer (NSCLC) (3%–4%) and is associated with a poor prognosis. With the advent of selective MET inhibitors such as capmatinib, tepotinib, and savolitinib, the outcome for these patients was significantly improved. Here, we report a 76-year-old male patient with marginally resectable stage IIIB lung adenocarcinoma harboring METex14 who was successfully treated with savolitinib for neoadjuvant therapy. An 82% shrinkage of the primary tumor was observed, and only 5% of the tumor was viable by pathology in the following radical surgery. A dozen of studies tested the efficiency of neoadjuvant immunotherapy or immunochemotherapy, but for NSCLC with driver mutations, neoadjuvant targeted therapy might be more appropriate. We advocated the neoadjuvant MET TKI treatment for NSCLC.