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The Cdk8 kinase module (CKM) in Mediator, comprising Med13, Med12, CycC, and Cdk8, regulates RNA polymerase II transcription through kinase-dependent and -independent functions. Numerous pathogenic mutations causative for neurodevelopmental disorders and cancer congregate in CKM subunits. However, the structure of the intact CKM and the mechanism by which Cdk8 is non-canonically activated and functionally affected by oncogenic CKM alterations are poorly understood. Here, we report a cryo-electron microscopy structure of Saccharomyces cerevisiae CKM that redefines prior CKM structural models and explains the mechanism of Med12-dependent Cdk8 activation. Med12 interacts extensively with CycC and activates Cdk8 by stabilizing its activation (T-)loop through conserved Med12 residues recurrently mutated in human tumors. Unexpectedly, Med13 has a characteristic Argonaute-like bi-lobal architecture. These findings not only provide a structural basis for understanding CKM function and pathological dysfunction, but also further impute a previously unknown regulatory mechanism of Mediator in transcriptional modulation through its Med13 Argonaute-like features.

A major challenge in finding a cure for HIV-1/AIDS is the difficulty in identifying and eradicating persistent reservoirs of replication-competent provirus. Long noncoding RNAs (lncRNAs, >200 nucleotides) are increasingly recognized to play important roles in pathophysiology. Here, we report the first genome-wide expression analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs). We identified an lncRNA, which we named HIV-1-enhanced lncRNA (HEAL), that is upregulated by HIV-1 infection of MDMs, microglia, and T lymphocytes. Peripheral blood mononuclear cells of HIV-1-infected individuals show elevated levels of HEAL Importantly, HEAL is a broad enhancer of multiple HIV-1 strains because depletion of HEAL inhibited X4, R5, and dual-tropic HIV replications and the inhibition was rescued by HEAL overexpression. HEAL forms a complex with the RNA-binding protein FUS, which facilitates HIV replication through at least two mechanisms: (i) HEAL-FUS complex binds the HIV promoter and enhances recruitment of the histone acetyltransferase p300, which positively regulates HIV transcription by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin-dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Notably, HEAL knockdown and knockout mediated by RNA interference (RNAi) and CRISPR-Cas9, respectively, prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment in vitro Our results suggest that silencing of HEAL or perturbation of the HEAL-FUS ribonucleoprotein complex could provide a new epigenetic silencing strategy to eradicate viral reservoirs and effect a cure for HIV-1/AIDS.IMPORTANCE Despite our increased understanding of the functions of lncRNAs, their potential to develop HIV/AIDS cure strategies remains unexplored. A genome-wide analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs) was performed, and 1,145 differentially expressed lncRNAs were identified. An lncRNA named HIV-1-enhanced lncRNA (HEAL) is upregulated by HIV-1 infection and promotes HIV replication in T cells and macrophages. HEAL forms a complex with the RNA-binding protein FUS to enhance transcriptional coactivator p300 recruitment to the HIV promoter. Furthermore, HEAL knockdown and knockout prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment, suggesting HEAL as a potential therapeutic target to cure HIV-1/AIDS.

Long noncoding RNAs (lncRNAs) can regulate target gene expression by acting in cis (locally) or in trans (non-locally). Here, we performed genome-wide expression analysis of Toll-like receptor (TLR)-stimulated human macrophages to identify pairs of cis-acting lncRNAs and protein-coding genes involved in innate immunity. A total of 229 gene pairs were identified, many of which were commonly regulated by signaling through multiple TLRs and were involved in the cytokine responses to infection by group B Streptococcus We focused on elucidating the function of one lncRNA, named lnc-MARCKS or ROCKI (Regulator of Cytokines and Inflammation), which was induced by multiple TLR stimuli and acted as a master regulator of inflammatory responses. ROCKI interacted with APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) to form a ribonucleoprotein complex at the MARCKS promoter. In turn, ROCKI-APEX1 recruited the histone deacetylase HDAC1, which removed the H3K27ac modification from the promoter, thus reducing MARCKS transcription and subsequent Ca2+ signaling and inflammatory gene expression. Finally, genetic variants affecting ROCKI expression were linked to a reduced risk of certain inflammatory and infectious disease in humans, including inflammatory bowel disease and tuberculosis. Collectively, these data highlight the importance of cis-acting lncRNAs in TLR signaling, innate immunity, and pathophysiological inflammation.

Thousands of large intergenic noncoding RNAs (lincRNAs) have been identified in the mammalian genome, many of which have important roles in regulating a variety of biological processes. Here, we used a custom microarray to identify lincRNAs associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. Among them, linc1992 was shown to be expressed in many human tissues and was required for induction of TNFα expression. Linc1992 bound specifically to heterogenous nuclear ribonucleoprotein L (hnRNPL) and formed a functional linc1992-hnRNPL complex that regulated transcription of the TNFα gene by binding to its promoter. Transcriptome analysis revealed that linc1992 was required for expression of many immune-response genes, including other cytokines and transcriptional and posttranscriptional regulators of TNFα expression, and that knockdown of linc1992 caused dysregulation of these genes during innate activation of THP1 macrophages. Therefore, we named linc1992 THRIL (TNFα and hnRNPL related immunoregulatory LincRNA). Finally, THRIL expression was correlated with the severity of symptoms in patients with Kawasaki disease, an acute inflammatory disease of childhood. Collectively, our data provide evidence that lincRNAs and their binding proteins can regulate TNFα expression and may play important roles in the innate immune response and inflammatory diseases in humans.

There are significant challenges for medical practitioners who have to navigate complex clinical, legal, ethical and administrative considerations in the prescription of controlled medications in the treatment of insomnia. This commentary examines the changing landscape and reframing of risks associated with the use of benzodiazepines and Z-drugs in light of recent legal precedents based on the frameworks of the Ethical Code and Ethical Guidelines, and the Prescribing of Benzodiazepines Guidelines (MOH Clinical Practice Guidelines 2/2008). The recent ruling from the Court of Three Judges has shone a spotlight on rigorous justification in instances where there is deviation from established treatment guidelines and thorough risk-benefit analysis, particularly when considering off-label use of medications, which is not uncommon in the clinical setting. While the risks of long-term prescription of benzodiazepines should never be discounted, preservation of a patient’s functioning and current quality of life should also be taken into consideration in the risk-benefit analysis. The complexities of transitioning patients from sedative hypnotics to alternative medications are also addressed, with an advocation for licensed medications with established safety profiles.

Abstract Different from previous studies on the motives of compensatory consumption, this review focuses on the strategies of compensatory consumption. This literature review aims to introduce two main strategies for compensatory consumption, within-domain and across-domain compensation. Within-domain compensation is a consumption strategy to repair a self-discrepancy in a specific domain, while across-domain compensation refers to a consumption strategy that consumers restore their global self-worth by affirming themselves in other important domains yet unrelated to the self-discrepancies. Based on the SPAR-4-SLR protocol to assemble, arrange and assess literature published from 2008 to 2023 Q1, we chose 65 articles to review. In order to gain a deeper understanding of within-domain and across-domain compensation, we systematically review the existing literature in the field and propose a framework based on the ADO models. Lastly, we discuss the various research directions for within-domain and across-domain compensation from the viewpoint of theory, context, characteristics, and methodology according to the TCCM framework. Researchers, marketers, and advertisers can learn about the latest research related to compensatory consumption strategies in this article.

Abstract Oncolytic virotherapy is emerging as a promising therapeutic avenue for cancer treatment, harnessing both innate and tumor-specific immune responses for targeted tumor elimination. In this study, we present a novel oncolytic virus (oHSV1-IL15B) derived from herpes simplex virus-1 (HSV-1), armed with IL-15/IL-15Rα complex, with a focus on treating colon cancer combined with oncolytic HSV-1 expressing anti-PD-1 antibody (oHSV1-aPD1). Results from our study reveal that recombinant oHSV-1 virus equipped with IL-15/IL-15Rα complex exhibited significant anti-tumor effects in a murine CT26 colon adenocarcinoma model. Notably, oHSV1-IL15B combined with oHSV-1-aPD1 demonstrates superior tumor inhibition and prolonged overall survival compared to oHSV1-mock and monotherapy groups. Further exploration highlights the impact of oHSV1-IL15B, oHSV-1-aPD1 and combined group on antitumor capacity, revealing a substantial increase in CD8+ T and CD4+ T cell proportions of CT26-bearing BALB/c mice and promoting apoptosis in tumor tissue. The study emphasizes the pivotal role of cytotoxic CD8+T cells in oncolytic virotherapy, demonstrating that recombinant oHSV1-IL15B combined with oncolytic HSV-1-aPD1 induces a robust tumor-specific T cell response. RNA sequence analysis highlighted oHSV1-IL15B combined with oHSV1-aPD1 improved tumors immune microenvironment on immune response, antiviral response-related genes and apoptosis-related genes, which contributed to anti-tumor immunotherapy. The findings underscore the promising antitumor activity achieved through the combination of IL-15/IL-15Rα complex and anti-PD-1 antibody with oHSV-1. This research opens avenues for diverse therapeutic strategies, suggesting the potential of synergistically utilizing cytokines and anti-PD-1 antibody with oncolytic viruses to enhance immunotherapy for cancer management.

Psychological safety is the belief that one will not be punished or humiliated for speaking up, sharing ideas, raising concerns, or making mistakes. There are various threats to psychological safety in health professions education (HPE). This commentary applies Clark’s model of psychological safety (Inclusion Safety, Learner Safety, Contributor Safety, Challenger Safety) to five different HPE settings (classroom instructions, clinical training, simulation-based training, online instructions, interprofessional education). Setting-specific threats and strategies for enhancing psychological safety are discussed.

IntroductionExtracellular vesicles (EVs) shed from tumor cells into peripheral circulation or other body fluids are promising biomarkers for cancer diagnosis with enormously long circulation. Consequently, precise methods for differentiating normal and tumor-associated EVs (TAEs) are required.MethodsThis study used quantifiable antibody-DNA conjugate-assisted quantitative methods combined with proximity ligation technology to detect TAEs. The antibody-DNA conjugate contained one antibody associated with three oligonucleotides for signal amplification. The antibody in the conjugate can recognize the surface tumor antigens of TAEs. Simultaneously, DNA in the conjugate is attached to the surfaces of TAEs and holds the signal amplification post, converting protein identities to DNA amplification for protein detection, even at the molecular level.ResultsThese findings revealed that TAEs can be quantitatively detected using DNA-mediated quantitative polymerase chain reaction (qPCR). Antibody-DNA conjugates were used to recognize the epithelial cell adhesion molecule (EpCAM) antigen on the TAE surface and quantify the antigen using qPCR for cancer analysis.DiscussionThis method proposed a new quantitative detection approach for TAEs, which aim to identify specific EV-associated markers for diagnostic or therapeutic, this method could inspire a new idea for tumor diagnosis and detection of other diseases.

Abstract Bladder cancer (BC) poses high morbidity and mortality, with urinary exosomal microRNA (miR)‐21 showing potential value in its diagnosis and prognosis, and we probed its specific role. We prospectively selected 116 BC patients and 116 healthy volunteers as the BC and control groups, respectively. BC urinary exosomal miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, and miR‐4454 relative expression levels were assessed. The correlations between clinical indexes and urinary exosomal miR‐21, prognostic value of miR‐21, and diagnostic value of the five candidate miRNAs, urine cytology, and miRNA joint diagnostic panel for BC and urinary exosomal miR‐21, miR‐4454, and urine cytology for Ta‐T1 and T2‐T4 stage BC were analyzed. Urinary exosomal miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, and miR‐4454 were highly expressed in BC patients. miR‐146a‐5p, miR‐93‐5p, miR‐663b, miR‐21, miR‐4454, miRNA combined diagnostic panel, and urine cytology had certain diagnostic value for BC, with miR‐21, miR‐4454, and miRNA co‐diagnostic panel showing the highest diagnostic value. Collectively, urinary exosomal miR‐21 was closely related to Tumor‐Node‐Metastasis staging and grading in BC patients. Urinary exosomal miR‐21 had high diagnostic value for BC and Ta‐T1 and T2‐T4 stage BC, and had high predictive value for BC poor prognosis, providing an effective indicator for the occurrence, development, and prognostic assessment of BC.

Biaxial rotary tillage in dryland (DBRT) can complete biaxial rotary tillage with straw incorporation, secondary suppression, and ditching, and it has been previously studied in direct-seeded rice and wheat. However, the effects of DBRT on the mechanically transplanted rice yield and greenhouse gas emissions remain unclear. To evaluate the effects of DBRT on improving the food security of mechanically transplanted rice and reducing the greenhouse gas emissions, we conducted an experiment for two years with wheat straw incorporation. Three tillage methods were set up: DBRT, uniaxial rotary tillage in dryland and paddy (DPURT), and uniaxial rotary tillage in paddy (PURT). The results showed that compared with DPURT and PURT, DBRT increased the yield of machine-transplanted rice by 7.5–11.0% and 13.3–26.7%, respectively, while the seasonal cumulative CH4 emissions were reduced by 13.9–21.2% and 30.2–37.0%, respectively, and the seasonal cumulative N2O emissions were increased by 13.5–28.6% and 50.0–73.1%, respectively. Consequently, DBRT reduced the global warming potential by 10.7–15.5% and 23.7–28.6%, respectively, and the yield-scaled global warming potential by 18.2–21.8% and 36.4–39.3%, respectively, compared to DPURT and PURT. These results were mainly related to the fact that DBRT significantly reduced soil bulk density and increased soil redox potential (Eh). Therefore, implementing DBRT in machine-transplanted rice fields is feasible, which cannot only increase the rice yield, but also reduce the greenhouse gas emissions.

Abstract Objective To compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock. Method We conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3 −), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation. Results The post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p

Author(s): Kuang-Lei Tsai [1]; Xiaodi Yu [1]; Sneha Gopalan [2]; Ti-Chun Chao [3]; Ying Zhang [2]; Laurence Florens [2]; Michael P. Washburn [2, 4]; Kenji Murakami [5]; Ronald C. Conaway [...], The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 resolution cryo-electron microscopy map of a MediatorRNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

This study investigated the synergistic potential of an oncolytic herpes simplex virus armed with interleukin 12 (VT1092M) in combination with immune checkpoint inhibitors for enhancing antitumor responses. The potential of this combination treatment to induce systemic antitumor immunity was assessed using bilateral subcutaneous tumor and tumor re-challenge mouse models. The antitumor efficacy of various OV and ICI treatment combinations and the underlying mechanisms were explored through diverse analytical techniques, including flow cytometry and RNA sequencing. Using VT1092M, either alone or in combination with an anti-PD-L1 antibody, significantly reduced the sizes of both the injected and untreated abscopal tumors in a bilateral tumor mouse model. The combination therapy demonstrated superior antitumor efficacy to the other treatment conditions tested, which was accompanied by an increase in T cell numbers and CD8+ T cell activation. Results from the survival and tumor re-challenge experiments showed that the combination therapy elicited long-term, tumor-specific immune responses, which were associated with tumor clearance and prolonged survival. Immune cell depletion assays identified CD8+ T cells as the crucial mediators of systemic antitumor immunity during combination therapy. In conclusion, the combination of VT1092M and PD-L1 blockade emerged as a potent inducer of antitumor immune responses, surpassing the efficacy of each monotherapy. This synergistic approach holds promise for achieving robust and sustained antitumor immunity, with potential implications for preventing tumor metastasis in patients with cancer.

Ring-array photoacoustic tomography (PAT) system has been widely used in noninvasive biomedical imaging. However, the reconstructed image usually suffers from spatially rotational blur and streak artifacts due to the non-ideal imaging conditions. To improve the reconstructed image towards higher quality, we propose a concept of spatially rotational convolution to formulate the image blur process, then we build a regularized restoration problem model accordingly and design an alternating minimization algorithm which is called blind spatially rotational deconvolution to achieve the restored image. Besides, we also present an image preprocessing method based on the proposed algorithm to remove the streak artifacts. We take experiments on phantoms and in vivo biological tissues for evaluation, the results show that our approach can significantly enhance the resolution of the image obtained from ring-array PAT system and remove the streak artifacts effectively.

Abstract Targeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification of suitable degraders is essential for achieving effective protein degradation. Here, we present a non-covalent degrader construction strategy, based on a modular supramolecular co-assembly system consisting of two self-assembling peptide ligands that bind cell membrane receptors and the protein of interest simultaneously, resulting in targeted protein degradation. The developed lysosome-targeting co-assemblies (LYTACAs) can induce lysosomal degradation of extracellular protein IL-17A and membrane protein PD-L1 in several scavenger receptor A-expressing cell lines. The IL-17A-degrading co-assembly has been applied in an imiquimod-induced psoriasis mouse model, where it decreases IL-17A levels in the skin lesion and alleviates psoriasis-like inflammation. Extending to asialoglycoprotein receptor-related protein degradation, LYTACAs have demonstrated the versatility and potential in streamlining degraders for extracellular and membrane proteins.

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory, resistant to antiepileptic drugs, and has a high recurrence rate. The pathogenesis of temporal lobe epilepsy is complex and is not fully understood. Intracellular calcium dynamics have been implicated in temporal lobe epilepsy. However, the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown, and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice. In this study, we used a multi-channel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process. We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes. In particular, cortical spreading depression, which has recently been frequently used to represent the continuously and substantially increased calcium signals, was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from grade II to grade V. However, vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures. Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to grade I episodes. In addition, the latency of cortical spreading depression was prolonged, and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced. Intriguingly, it was possible to rescue the altered intracellular calcium dynamics. Via simultaneous analysis of calcium signals and epileptic behaviors, we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced, and that the end-point behaviors of temporal lobe epilepsy were improved. Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to different grades. Furthermore, the selective regulation of abnormal calcium signals in CA1 pyramidal neurons appears to effectively alleviate temporal lobe epilepsy, thereby providing a potential molecular mechanism for a new temporal lobe epilepsy diagnosis and treatment strategy.

Abstract Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.

Bacillus thuringiensis (Bt) has been extensively applied in agricultural pest management, posing a notable ecological risk to beneficial insects like Bombyx mori (silkworms). However, the toxicological mechanisms of Bt at low concentrations on silkworms remain largely unexplored. In this study, we determined the LC50 (96 h) of Bt for fifth-instar silkworm larvae to be 0.08 × 10−3 mg/L. Exposure to a sub-lethal concentration of Bt (1/2 LC50) led to significant reductions in body weight, pupal size, and the weights of both the whole cocoon and cocoon shell. Histopathological and ultrastructural examinations revealed that Bt exposure caused severe damage to the microvilli and epidermal cells of the midgut. Transcriptome sequencing of the midgut identified 290 differentially expressed genes (DEGs), with these genes predominantly involved in metabolic processes and apoptotic pathways. Notably, apoptosis-related genes such as Apaf-1 and Caspase-3 were upregulated by 5.08-fold and 1.27-fold, respectively. Further validation through TUNEL assays and Western blotting analysis confirmed a significant activation of apoptotic signaling. These findings suggested that low concentrations of Bt could trigger apoptotic pathways in the midgut of silkworm larvae, providing valuable insights into the toxicological evaluation of Bt at sub-lethal doses in insect species.

Objective: To explore the feasibility of transvaginal ultrasound measurement of uterocervical angle (UCA) and cervical length (CL) in early and mid-pregnancy and evaluate their combined prediction of spontaneous preterm birth (sPTB) in singleton pregnancies.Patients and Methods: This retrospective study comprised 274 pregnant women who underwent transvaginal ultrasound measurement of CL in mid-pregnancy (15–23+6 weeks); in 75 among them, CL also had been measured in early-pregnancy (37 weeks gestation) according to delivery before or after 37 weeks, respectively. In the preterm group, 35 patients delivered before 34 weeks and the remaining 114 delivered between 34 and 37 weeks.Results: The optimal threshold of CL to predict preterm birth risk in women with 0.01), but only in mid-pregnancy (p < 0.01). There was a negative correlation between UCA and gestational week at delivery (r = −0.361, p < 0.001) and a positive correlation between CL and gestational week at delivery (r = 0.346, p < 0.001) in mid-pregnancy. The proportion of deliveries at 105°, and the proportion of deliveries between 35 and 37 weeks was highest when the UCA was between 95° and 105°. The proportion of deliveries at

We present an application of short-pulse laser-generated hard x rays for the diagnosis of indirectly driven double shell targets. Cone-inserted double shell targets were imploded through an indirect drive approach on the upgraded SG-II laser facility. Then, based on the point-projection hard x-ray radiography technique, time-resolved radiography of the double shell targets, including that of their near-peak compression, were obtained. The backlighter source was created by the interactions of a high-intensity short pulsed laser with a metal microwire target. Images of the target near peak compression were obtained with an Au microwire. In addition, radiation hydrodynamic simulations were performed, and the target evolution obtained agrees well with the experimental results. Using the radiographic images, areal densities of the targets were evaluated.

Tick-borne diseases are of substantial concern worldwide for both humans and animals, and dogs are frequently exposed to tick infestation. The aim of this study was to examine tick infestation of pet and stray dogs in Guangzhou, Southern China, as well as tick-borne pathogens of randomly sampled ticks. Ticks were found on 118 (14.1% [95% confidence interval; CI: 13.6–14.6]) out of 836 animals in four veterinary clinics and two shelters. A total of 280 individual ticks were collected from tick-infested dogs. Rhipicephalus sanguineus sensu lato (s.l.) was identified. PCR tests were conducted to detect six tick-borne pathogens in 280 ticks. The prevalence of tick-borne pathogens was 5.3% for Babesia spp., including Babesia vogeli (5.0% [95% CI: 4.3–6.3]) and Babesia gibsoni (0.3% [95% CI: 4.3–6.3]). These results indicated that R. sanguineus s.l. was the tick species found in dogs in Guangzhou city, and that dogs were at risk to exposure to babesiosis, implying the need for surveillance for this disease in dogs in this region.

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.

Hyperspectral imaging techniques can generate continuous narrowband images with a high spectral resolution. However, owing to environmental disturbances, atmospheric effects, and hardware limitations of hyperspectral imaging sensors, captured hyperspectral images (HSIs) often contain complex noises that significantly degrades their quality and limits their utility. In this article, we design a deep tensor attention module based on a canonical-polyadic (CP) decomposition of a feature tensor, referred to as a deep CP attention module (DCPAM), which can disentangle spatial and channel information and further enhance the topological structure of features. It has been shown that the DCPAM is effective and relatively simple to integrate into some well-known network architectures. And taking the network with the DCPAM as a deep prior, we propose a deep tensor attention prior network (DTAPNet) for HSI denoising tasks. Extensive experiments on simulated and real HSIs demonstrate that our proposed DTAPNet outperforms existing state-of-the-art HSI denoising models.

Radiation resistance has always been one of the main obstacles to tumor radiotherapy. Therefore, understanding the mechanisms underlying radiotherapy resistance is a focus of research. In this study, we induced two radiation-resistant cell lines to mimic the radiation resistance of NSCLC and investigated the mechanisms of radiotherapy resistance. Cell radiosensitivity was analyzed by single-cell gel electrophoresis, colony formation and tumor sphere formation assays. A wound healing assay was used to analyze cell migration. Western blotting and siRNA were used to identify the potential mechanism. In animal model experiments, xenograft tumors were used to verify the difference between radiotherapy-resistant and nonresistant NSCLC models after radiotherapy. Our results showed that NSCLC radiation-resistant cells exhibited more radioresistance and migratory abilities under low-dose irradiation. The expression of LIMK2 and p-CFL1 were upregulated in NSCLC radiation-resistant cells. Knockdown of LIMK2 significantly enhanced the radiosensitivity of NSCLC-resistant cells. In vivo, low-dose radiotherapy suppressed tumor growth, induced apoptosis and upregulated the expression of LIMK2 in xenograft tumors. However, radiotherapy had little effect on the NSCLC radiation resistance model. In conclusion, NSCLC radiation-resistant cells exhibit more radioresistance and migratory ability under low-dose irradiation. Strikingly, knockdown of LIMK2 enhanced the radiosensitivity of NSCLC-resistant cells.

IntroductionThis study aimed to evaluate the feasibility of using general Raman spectroscopy as a method to screen for breast cancer. The objective was to develop a machine learning model that utilizes Raman spectroscopy to detect serum samples from breast cancer patients, benign cases, and healthy subjects, with puncture biopsy as the gold standard for comparison. The goal was to explore the value of Raman spectroscopy in the differential diagnosis of breast cancer, benign lesions, and healthy individuals.MethodsIn this study, blood serum samples were collected from a total of 333 participants. Among them, there were 129 cases of tumors (pathologically diagnosed as breast cancer and labeled as cancer), 91 cases of benign lesions (pathologically diagnosed as benign and labeled as benign), and 113 cases of healthy controls (labeled as normal). Raman spectra of the serum samples from each group were collected. To classify the normal, benign, and cancer sample groups, principal component analysis (PCA) combined with support vector machine (SVM) was used. The SVM model was evaluated using a cross-validation method. ResultsThe results of the study revealed significant differences in the mean Raman spectra of the serum samples between the normal and tumor/benign groups. Although the mean Raman spectra showed slight variations between the cancer and benign groups, the SVM model achieved a remarkable prediction accuracy of up to 98% for classifying cancer, benign, and normal groups. DiscussionIn conclusion, this exploratory study has demonstrated the tremendous potential of general Raman spectroscopy as a clinical adjunctive diagnostic and rapid screening tool for breast cancer.

Background2’,5’-oligoadenylate synthetase 1 (OAS1), has been reported as a tumor driver gene in breast carcinoma and pancreatic carcinoma. However, the role of OAS1 in most tumors has not been reported.MethodsThe original data of 35 tumor types were down load from the TCGA (The Cancer Genome Atlas) database and Human Protein Atlas (HPA) database. TIMER2, Kmplot, UALCAN, and TISIDB tools were used to investigate the expression and function of OAS1, and the role of OAS1 in prognosis, diagnostic value, and immune characteristics of pan-cancer. LUAD and PRAD cell lines, A549, H1975, PC-3 and C4-2 were utilized to perform cell function tests.ResultsOAS1 expression was up-regulated in 12 tumor types and down-regulated in 2 tumor types. High OAS1 expression was correlated with poor prognosis in 6 tumor types, while high OAS1 expression was correlated with good prognosis in 2 tumor types. OAS1 was correlated with molecular subtypes in 8 tumor types and immune subtypes in 12 tumor types. OAS1 was positively associated with the expression of numerous immune checkpoint genes and tumor mutational burden (TMB). OAS1 had potential diagnostic value in 15 tumor types. Silence of OAS1 significantly inhibited the cell proliferation ability, and promoted G2/M cell cycle arrest of LUAD and PRAD cells. Meanwhile, silence of OAS1 enhanced cisplatin-induced apoptosis of LUAD and PRAD cells, but weakened cell migration.ConclusionThis pan-cancer study suggests that OAS1can be used as a molecular biomarker for prognosis in pan-cancer and may play an important role in tumor immune response.

Load-capacity has always been one of the performances that is paid much attention to in the development of bevel gear transmission applications. Consequently, the mathematical model of novel bevel gear with high load-capacity based on geometric elements is proposed in this paper, which could be applied to the aviation, aerospace and other fields. In parallel, the design principle and design method of the novel bevel gear are introduced in detail. Subsequently, the conditions for tooth surface continuity and non-interference are derived. Furthermore, the model of novel bevel gear is established. Finally, the load-bearing characteristics are analyzed, revealing that an increase in the number of contact points could significantly enhance the load capacity of the bevel gear pairs. When the load torque applied to bevel gear II is 100 Nm, the contact pressure endured by the bevel gear pair with five-point contact is decreased by 41.37% compared to the bevel gear pair with single-point contact. When the number of contact points is the same, increasing the distance between the contact points could also reduce the contact stress. This provides strong theoretical support for the application of the bevel gear based on the geometric elements.

Abstract The research on driving mechanisms of urban land expansion is hot topic of land science. However, the relative importance of anthropogenic-natural factors and how they affect urban land expansion change are still unclear. Based on the Google Earth Engine platform, this study used the support vector machine classifier to extract land-use datasets of Mentougou district of Beijing, China from 1990 to 2016. Supported by machine-learning approaches, multiple linear regression (MLR) and random forests (RF) were applied and compared to identify the influential factors and their relative importance on urban land expansion. The results show: There was a continuous growth in urban land expansion from 1990 to 2016, the increased area reached 6097.42 ha with an average annual rate of 8.01% and average annual intensity rate of 2.57%, respectively. Factors such as elevation, risk of goaf collapse, accessibility, local fiscal expenditure, industrial restructuring, per capita income in rural area, GDP were important drivers of urban land expansion change. The model comparison indicated that RF had greater ability than MLR to identify the non-linear relationships between urban land expansion and explanatory variables. The influencing factors of urban land expansion should be comprehensively considered to regulate new land policy actions in Mentougou.

Background: Delayed wound healing, a common problem in patients with diabetes mellitus (DM), is associated with impaired keratinocyte autophagy. Epigallocatechin gallate (EGCG), a catechin, has been proven to promote diabetic wound healing. This study aims to explore the therapeutic mechanism of EGCG on diabetic wound healing. Methods: High glucose (HG)-induced keratinocytes and streptozotocin (STZ)-induced DM rats were prepared and intervened with EGCG to examine its therapeutic effects in in vivo and in vitro settings. The AMPK inhibitor, Compound C, was utilized to determine whether EGCG exerted its therapeutic effects through the AMPK/ULK1 pathway. Results: In vitro, EGCG improved HG-induced autophagy impairment in keratinocytes by increasing LC3II/LC3I, Becline1, and ATG5 levels and decreasing p62 level. Mechanically, EGCG activated the AMPK/ULK1 pathway, thereby promoting keratinocyte autophagy through the phosphorylation of AMPK and ULK1. Notably, EGCG promoted the proliferation, migration, synthesis and release of C-C motif chemokine ligand 2 (CCL2) in HG-treated keratinocytes. Furthermore, EGCG indirectly promoted the activation of fibroblasts, as evidenced by increased alpha-smooth muscle actin (α-SMA) and Collagen I levels. In vivo, EGCG promoted wound healing in DM rats, primarily by reducing inflammatory infiltration and increasing granulation tissue to promote wound epithelialization. Besides, EGCG promoted ATG5, KRT10, KRT14, TGF-β1, Collagen I, and α-SMA expressions in the neonatal epithelial tissues of DM rats. However, the use of Compound C reversed the effects of EGCG. Conclusions: These findings indicated that EGCG restored keratinocyte autophagy to promote diabetic wound healing through the AMPK/ULK1 pathway.