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Gaurenoglaea is a genus belonging to the tribe Xylenini. Since its establishment more than ten years ago, this genus has included only two species.A new species of the genus Gaurenoglaea Ronkay, Ronkay, Gyulai & Hacker, 2010, G. medogensis sp. nov. is described and illustrated from Xizang Autonomous Region, south-western China. The new species can be distinguished from the previous Gaurenoglaea species by the differences of forewing cilia and aedeagus. A key to the Gaurenoglaea species, based on morphology, is provided.

Cholangiocarcinoma is one of the most lethal human cancers, and chemotherapy failure is a major cause of recurrence and poor prognosis. We previously demonstrated that miR-200 family members are downregulated in clinical samples of cholangiocarcinoma and inhibit cholangiocarcinoma tumorigenesis and metastasis. However, the role of differentially expressed miR-200b-3p in 5-fluorouracil chemosensitivity remains unclear. Here, we examined how miR-200b-3p modulates 5-fluorouracil chemosensitivity in cholangiocarcinoma. We observed that miR-200b-3p was associated with 5-fluorouracil sensitivity in cholangiocarcinoma and increased 5-fluorouracil-induced mitochondrial apoptosis in cholangiocarcinoma cells. Mechanistically, miR-200b-3p suppressed autophagy in cholangiocarcinoma cells to mediate 5-fluorouracil sensitivity. Further, we identified KLF4 as an essential target of miR-200b-3p in cholangiocarcinoma. Notably, the miR-200b-3p/KLF4/autophagy pathway augmented the chemosensitivity of cholangiocarcinoma cells to 5-fluorouracil. Our findings underscore the key role of miR-200b-3p in chemosensitivity to 5-fluorouracil and highlight the miR-200b-3p/KLF4/autophagy axis as a potential therapeutic target for cholangiocarcinoma.

In gestational diabetes mellitus (GDM), adipose tissue undergoes metabolic disturbances and chronic low-grade inflammation. Alternative polyadenylation (APA) is a post-transcriptional modification mechanism that generates mRNA with variable lengths of 3' untranslated regions (3'UTR), and it is associated with inflammation and metabolism. However, the role of APA in GDM adipose tissue has not been well characterized. In this study, we conducted transcriptomic and proteomic sequencing on subcutaneous and omental adipose tissues from both control and GDM patients. Using Dapars, a novel APA quantitative algorithm, we delineated the APA landscape of adipose tissue, revealing significant 3'UTR elongation of mRNAs in the GDM group. Omental adipose tissue exhibited a significant correlation between elongated 3'UTRs and reduced translation levels of genes related to metabolism and inflammation. Validation experiments in THP-1 derived macrophages (TDMs) demonstrated the impact of APA on translation levels by overexpressing long and short 3'UTR isoforms of a representative gene LRRC25. Additionally, LRRC25 was validated to suppress proinflammatory polarization in TDMs. Further exploration revealed two underexpressed APA trans-acting factors, CSTF3 and PPP1CB, in GDM omental adipose tissue. In conclusion, this study provides preliminary insights into the APA landscape of GDM adipose tissue. Reduced APA regulation in GDM omental adipose tissue may contribute to metabolic disorders and inflammation by downregulating gene translation levels. These findings advance our understanding of the molecular mechanisms underlying GDM-associated adipose tissue changes.

Abstract Purpose To research the therapeutic effects of 577 nm micropulse laser photocoagulation (MLP) treatment in early-stage central serous chorioretinopathy (CSCR) patients. Methods Twenty-two CSCR patients with 24 CSCR eyes were examined prior to MLP treatment. The examinations included best-corrected visual acuity (BCVA), fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), optical coherence tomography angiography (OCTA) and microperimetry. After MLP treatment, all the subjects were reviewed at 30 days. The BCVA, macular function on microperimetry, subretinal fluid (SRF) height of the macula on OCT, and choroid vascular density (VD) of the macular area on OCTA were compared before and after MLP treatment. The correlations between SRF height and visual function, choroid VD was analyzed separately. Results BCVA and macular function significantly increased and the SRF height of the macula significantly decreased after MLP treatment. BCVA and macular function were significantly negatively correlated with SRF height. The choroid VD was significantly increased after MLP treatment, and choroid VD in the leakage site part of the macula were significantly negatively correlated with the height of the SRF. A recurrent patient who received two MLP treatments also had a negative correlation between SRF and choroid VD during the course of disease. Conclusions 577 nm MLP is safe and effective for early-stage CSCR patients, and treatment can restore macular structure and function. The increase in choroid VD of leakage site part after treatment is one of the key effects of MLP treatment for early-stage CSCR patients.

Abstract Structural asymmetry is a subtle but pervasive property of the human brain, which has been found altered in various psychiatric and neurocognitive disorders. However, little is known regarding potential alterations of structural asymmetry underlying internet gaming disorder (IGD). Therefore, this study aimed to investigate the structural features of gray matter asymmetry in IGD. High-resolution structural magnetic resonance imaging data were collected from 104 individuals with IGD and 104 recreational game users (RGUs). We applied a whole-brain voxel-based asymmetry (VBA) approach to determine the asymmetrical aberrations of gray matter in relation to IGD. Furthermore, the local abnormalities of structural asymmetry were employed as features to examine the effect of classification using a support vector machine (SVM). The results indicated that individuals with IGD as compared to RGUs showed asymmetrical alterations of gray matter in the medial prefrontal cortex (mPFC), orbitofrontal cortex, precuneus, middle temporal gyrus, superior parietal lobule and inferior temporal gyrus, regions implicated in hedonic motivation, self-reflection, information integration and visuospatial attention processing. Moreover, these atypical asymmetrical features can distinguish IGD subjects from RGUs with high accuracy. These results suggested that disrupted structural asymmetry of motivational reward, visuospatial and default mode circuits might be potential biomarkers for identifying pathological gaming dependence. These findings extended our understanding of structural underpinnings of IGD and provided new insights for developing effective interventions to alleviate compulsive gaming usage.

Abstract Background As one of the world’s most important vegetable crops, eggplant production is often severely affected by verticillium wilt, leading to significant declines in yield and quality. Traditional multispectral disease-imaging equipment is expensive and complicated to operate. Low-cost multispectral devices cannot capture images and cover less information. The traditional approach to early disease diagnosis involves using multispectral disease-imaging equipment in conjunction with machine learning technology. However, this approach has significant limitations in early disease diagnosis, including challenges such as high costs, complex operation, and low model performance. Results The aim of this study was to combine low-cost multispectral cameras with deep learning technology to detect early stage Verticillium wilt in eggplant effectively. Using the Manual FS-3200T-10GE-NNC multispectral camera to perform multispectral imaging of the leaves of eggplant seedlings at the early infection stage, information fusion was performed on the collected multispectral images, and a five-channel image information fusion model was established. Image information fusion technology was combined with deep learning technology, among which the VGG16-triplet attention model performed the best, achieving a precision of 86.73% on the test set. Model validation on 48- and 72-hour data reached a precision of 75% and 82%, respectively, achieving an early diagnosis of Verticillium wilt. This highlighted the potential of multispectral cameras for early disease detection. Conclusions In this study, we successfully developed a method for the non-destructive detection of the early stages of eggplant wilt disease by combining multispectral imaging technology with deep learning algorithms. While ensuring high accuracy, this method significantly reduces the cost of experimental equipment. The application of this method can reduce the cost of agricultural equipment and provide a scientific basis for agricultural production practices, helping to reduce losses caused by diseases.

Abstract Pyroptosis is a lytic and inflammatory form of gasdermin protein-mediated programmed cell death that is typically initiated by inflammasomes. The inflammasome response is an effective mechanism for eradicating germs and cancer cells in the event of cellular injury. The gasdermin family is responsible for initiating pyroptosis, a process in which holes are made in the cell membrane to allow inflammatory chemicals to escape. Mounting evidence indicates that pyroptosis is critical for controlling the development of cancer. In this review, we provide a general overview of pyroptosis, examine the relationship between the primary elements of pyroptosis and tumors, and stress the necessity of pyroptosis-targeted therapy in tumors. Furthermore, we explore its dual nature as a double-edged sword capable of both inhibiting and facilitating the growth of cancer, depending on the specific conditions. Ultimately, pyroptosis is a phenomenon that has both positive and negative effects on tumors. Using this dual impact in a reasonable manner may facilitate investigation into the initiation and progression of tumors and offer insights for the development of novel treatments centered on pyroptosis.

Abstract Background Habenaria, a genus in the family Orchidaceae, are the nearly cosmopolitan orchids, and most species have significant medicinal and ornamental values. Despite the morphological and molecular data that have been studied in recent years, the phylogenetic relationship is still unclear. Results We sequenced, assembled, and annotated the chloroplast (cp) genomes of two species (Habenaria aitchisonii Rchb.f. and Habenaria tibetica Schltr.ex Limpricht) of Habenaria grown on the Qinghai-Tibetan Plateau (QTP), and compared them with seven previously published cp genomes which may aid in the genomic profiling of these species. The two genomes ranged from 155,259–155,269 bp in length and both included 132 genes, encoding 86 proteins, 38 tRNAs and 8 rRNAs. In the cp genomes, the tandem repeats (797), SSRs (2195) and diverse loci (3214) were identified. Comparative analyses of codon usage, amino frequency, microsatellite, oligo repeats and transition and transversion substitutions revealed similarities between the species. Moreover, we identified 16 highly polymorphic regions with a nucleotide diversity above 0.02, which may be suitable for robust authentic barcoding and inferring in the phylogeny of Habenaria species. Among the polymorphic regions, positive selection was significantly exerted on several genes, such as cemA, petA, and ycf1. This finding may suggest an important adaptation strategy for the two Habenaria species on the QTP. The phylogenetic relationship revealed that H. aitchisonii and H. tibetica were more closely related to each other than to the other species, and the other seven species were clustered in three groups. In addition, the estimated divergence time suggested that the two species separated from the others approximately 0.39 Mya in the Neogene period. Our findings also suggest that Habenaria can be divided into different sections. Conclusions The results of this study enriched the genomics resources of Habenaria, and SSR marker may aid in the conservation management of two endangered species.

Abstract Purpose Breast cancer (BRCA) is the most common malignant tumor among women, characterized by high incidence rates and mortality rates. Oxidative stress and immunity, particularly in relation to mitochondria, have emerged as pivotal factors in breast carcinogenesis. Nonetheless, limited research has explored the specific contribution of mitochondrial oxidative stress to the prognosis of BRCA. Method In this study, we conducted univariate and multivariate Cox regression analyses to pinpoint independent prognostic genes associated with mitochondrial oxidative stress (MOSRGs) and their correlation with BRCA clinical outcomes. Subsequently, we developed a robust and accurate MOS scoring system for BRCA patients based on these identified independent prognostic MOSRGs. Result Our findings were further substantiated by immune infiltration and somatic mutation analyses, providing additional evidence that the MOS scoring system holds predictive value for clinical outcomes in patients and correlates directly with three subtypes of BRCA. In vitro experiments in the MCF7 cell and breast tissue further verified the mRNA and protein expression level of independent prognostic genes, validating the consistency of the MOS prognostic signatures in BRCA. Conclusion This research has unveiled a novel prognostic scoring system, providing valuable insights for improving patient prognosis assessment and developing individualized treatment strategies in BRCA patients.

Abstract Background Neurocognitive impairment is one of the prominent manifestations of major depressive disorder (MDD). Childhood trauma enhances vulnerability to developing MDD and contributes to neurocognitive dysfunctions. However, the distinct impacts of different types of childhood trauma on neurocognitive processes in MDD remain unclear. Methods This study comprised 186 individuals diagnosed with MDD and 268 healthy controls. Childhood trauma was evaluated using the 28-item Childhood Trauma Questionnaire-Short Form. Neurocognitive abilities, encompassing sustained attention, vigilance, visual memory, and executive functioning, were measured by the Cambridge Neuropsychological Testing Automated Battery. Results Multivariable linear regressions revealed that childhood trauma and MDD diagnosis were independently associated with neurocognitive impairment. Physical neglect was associated with impaired visual memory and working memory. MDD diagnosis is associated with working memory and planning. Interactive analysis revealed that physical/sexual abuse was associated with a high level of vigilance and that emotional neglect was linked with better performance on cognitive flexibility in MDD patients. Furthermore, childhood emotional abuse, physical abuse, and emotional neglect were revealed to be risk factors for developing early-onset, chronic depressive episodes. Conclusion Thus, specific associations between various childhood traumas and cognitive development in depression are complex phenomena that need further study.

Abstract Background Information on the comparison of blood microbiota between human immunodeficiency virus (HIV)-infected and HIV-uninfected patients with suspected sepsis by metagenomic next-generation sequencing (mNGS) is limited. Methods Retrospectively analysis was conducted in HIV-infected and HIV-uninfected patients with suspected sepsis at Changsha First Hospital (China) from March 2019 to August 2022. Patients who underwent blood mNGS testing were enrolled. The blood microbiota detected by mNGS were analyzed. Results A total of 233 patients with suspected sepsis who performed blood mNGS were recruited in this study, including 79 HIV-infected and 154 HIV-uninfected patients. Compared with HIV-uninfected patients, the proportions of mycobacterium (p = 0.001), fungus (p

Abstract Background Postoperative pain (PP) is a dynamic process that reflects the complex interplay between symptoms, treatment, and patient experiences, and its intensity is reportedly primarily related to the severity of surgical trauma. However, no large-scale national database-based study has hitherto been conducted to assess the occurrence and features related to PP following breast cancer (BC) surgery. Methods In this retrospective analysis, we screened BC surgery cases between 2015 and 2019 within the National Inpatient Sample (NIS) Database, utilizing the International Classification of Diseases (ICD) 10th edition clinical modification codes. The researchers identified patients who developed PP and compared them to those who did not. Factors associated with PP were then screened: patient demographics (age and race), hospital characteristics (type of insurance, bed size, teaching status, type of admission, location, and hospital area), length of stay (LOS), total cost during hospitalization, inpatient mortality, comorbidities, and perioperative complications. Data were analyzed using descriptive statistics. Multivariate logistic regression analysis was used to determine the independent risk factors for postoperative pain in BC surgery. Results 39,870 BC surgery cases were identified over a five-year period from 2015 to 2019. The overall occurrence of PP following breast cancer surgery was 6.15% (2,387 cases), with a slight upward trend every year. Significant racial disparities were observed, Whites associated with a higher incidence of PP (P

Abstract Epicardial adipose tissue (EAT) significantly contributes to the progression of cardiovascular diseases (CVDs). However, manually quantifying EAT volume is labor-intensive and susceptible to human error. Although there have been some deep learning-based methods for automatic quantification of EAT, they are mostly uninterpretable and fail to harness the complete anatomical characteristics. In this study, we proposed an enhanced deep learning method designed for EAT quantification on coronary computed tomography angiography (CCTA) scan, which integrated both data-driven method and specific morphological information. A total of 108 patients who underwent routine CCTA examinations were included in this study. They were randomly assigned to training set (n = 60), validation set (n = 8), and test set (n = 40). We quantified and calculated the EAT volume based on the CT attenuation values within the predicted pericardium. The automatic method demonstrated strong agreement with expert manual quantification, yielding a median Dice score coefficients (DSC) of 0.916 (Interquartile Range (IQR): 0.846–0.948) for 2D slices. Meanwhile, the median DSC for the 3D volume was 0.896 (IQR: 0.874–0.908) between these two measures, with an excellent correlation of 0.980 (p

Abstract Ferroptosis has emerged as a promising strategy for cancer treatment. Nevertheless, the efficiency of ferroptosis-mediated therapy remains a challenge due to high glutathione (GSH) levels and insufficient endogenous hydrogen peroxide in the tumor microenvironment. Herein, we presented a nitric-oxide (NO) boost-GSH depletion strategy for enhanced ferroptosis therapy through a multifunctional nanoplatform with near-infrared (NIR) triggered NO release. The nanoplatform, IS@ATF, was designed that self-assembled by loading the NO donor L-arginine (L-Arg), ferroptosis inducer sorafenib (SRF), and indocyanine green (ICG) onto tannic acid (TA)-Fe3+‒metal-phenolic networks (MPNs) modified with hydroxyethyl starch. Inside the tumor, SRF could inhibit GSH biosynthesis, impair the activation of glutathione peroxidase 4, and disrupt the ferroptosis defensive system. In conjunction with TA-Fe3+‒MPNs, which has cascaded Fenton catalytic activity, it could navigate the lethal ferroptosis to cancer cells. Upon NIR laser irradiation, the ICG-generated ROS oxidated L-Arg to a substantial quantity of NO, which further depleted the intracellular GSH and caused LPO accumulation, enhancing cell ferroptosis. Moreover, ICG also serves as a photothermal agent that can produce hyperthermia when exposed to irradiation, further potentiating ferroptosis therapy. In addition, the nanoplatform showed significantly improved tumor therapeutic efficacy and anti-metastasis efficiency. This work thus demonstrated that utilizing NO boost-GSH depletion to enhance ferroptosis induction is a feasible and promising strategy for cancer treatment. Graphical abstract

Abstract The tensor singular value decomposition‐based model has garnered increasing attention in addressing tensor recovery challenges. However, existing tensor recovery methods exhibit certain inherent limitations. Some ignore the simultaneous effects of noise and missing values, while most can't handle higher‐order tensors, which are not reflective of real‐world scenarios. The information redundancy within tensor data often leads to a prevailing low‐rank structure, making low‐rankness a vital prior in the tensor recovery process. To tackle this pressing issue, a robust low‐rank tensor recovery framework is proposed to rehabilitate higher‐order tensors corrupted by sparse noise and missing entries. In the model, the tensor nuclear norm derived for order‐d tensors (d ≥ 4) are employed as a representation of the low‐rank prior, while utilizing the L1‐norm to model the sparse noise. To solve the proposed model, an efficient Alternating direction method of multipliers algorithm is developed. A series of experiments are performed on synthetic and real‐world datasets. The results show that the superior performance of the method compared with other algorithms dedicated to addressing order‐d tensor recovery challenges. Notably, in scenarios where the data is severely compromised (noise ratio 40%, sample ratio 70%), the algorithm consistently outperforms its competitors, achieving significantly improved results.

Abstract Emotion recognition in user‐generated videos plays an essential role in affective computing. In general, visual information directly affects human emotions, so the visual modality is significant for emotion recognition. Most classic approaches mainly focus on local temporal information of videos, which potentially restricts their capacity to encode the correlation of long‐range context. To address this issue, a novel network is proposed to recognize emotions in videos. To be specific, a spatio‐temporal correlation‐aware block is designed to depict the long‐range correlations between input tokens, where the convolutional layers are used to learn the local correlations and the inter‐image cross‐attention is designed to learn the long‐range and spatio‐temporal correlations between input tokens. To generate diverse and challenging samples, a dual‐augmentation fusion layer is devised, which fuses each frame with its corresponding frame in the temporal domain. To produce rich video clips, a long‐range sampling layer is designed, which generates clips in a wide range of spatial and temporal domains. Extensive experiments are conducted on two challenging video emotion datasets, namely VideoEmotion‐8 and Ekman‐6. The experimental results demonstrate that the proposed method obtains better performance than baseline methods. Moreover, the proposed method achieves state‐of‐the‐art results on the two datasets. The source code of the proposed network is available at: https://github.com/JinChow/LRCANet.

Abstract A high-accuracy, continuous air temperature (Ta) dataset with high spatiotemporal resolution is essential for human health, disease prediction, and energy management. Existing datasets consider factors such as elevation, latitude, and surface temperature but insufficiently address meteorological and spatiotemporal factors, affecting accuracy. Additionally, no high-resolution dataset currently includes daily maximum (Tmax), minimum (Tmin), and mean (Tmean) temperatures generated using a unified methodology. Here, we introduce the four-dimensional spatiotemporal deep forest (4D-STDF) model, integrating 12 multisource factors, encompassing static and dynamic parameters, and six refined spatiotemporal factors to produce Ta datasets. This approach generates three high-accuracy Ta datasets at 1 km spatial resolution covering mainland China from 2003 to 2022. These datasets, in GeoTIFF format with WGS84 projection, comprise daily Tmax, Tmin, and Tmean. The overall RMSE are 1.49 °C, 1.53 °C, and 1.18 °C for the estimates. The 4D-STDF model can also be applied to other regions with sparse meteorological stations.

Abstract The influenza neuraminidase (NA) is a potential target for the development of a next-generation influenza vaccine, but its antigenicity is not well understood. Here, we isolate an anti-N6 human monoclonal antibody, named 18_14D, from an H5N6 avian influenza virus (AIV) infected patient. The antibody weakly inhibits enzymatic activity but confers protection in female mice, mainly via ADCC function. The cryo-EM structure shows that 18_14D binds to a unique epitope on the lateral surface of the N6 tetramer, preventing the formation of tightly closed NA tetramers. These findings contribute to the molecular understanding of protective immune responses to NA of AIVs in humans and open an avenue for the rational design of NA-based vaccines.

Abstract In patients with abdominal or pelvic tumors, radiotherapy can result in radiation-induced intestinal injury (RIII), a potentially severe complication for which there are few effective therapeutic options. Sitagliptin (SI) is an oral hypoglycemic drug that exhibits antiapoptotic, antioxidant, and anti-inflammatory activity, but how it influences RIII-associated outcomes has yet to be established. In this study, a pH-responsive metal-organic framework-based nanoparticle platform was developed for the delivery of SI (SI@ZIF-8@MS NP). These NPs incorporated mPEG-b-PLLA (MS) as an agent capable of resisting the effects of gastric acid, and are capable of releasing Zn2+ ions. MS was able to effectively shield these SI@ZIF-8 NPs from rapid degradation when exposed to an acidic environment, enabling the subsequent release of SI and Zn2+ within the intestinal fluid. Notably, SI@ZIF-8@MS treatment was able to mitigate radiation-induced intestinal dysbiosis in these mice. restored radiation-induced changes in bacterial composition. In summary, these data demonstrate the ability of SI@ZIF-8@MS to protect against WAI-induced intestinal damage in mice, suggesting that these NPs represent a multimodal targeted therapy that can effectively be used in the prevention or treatment of RIII.

Abstract Depression is usually accompanied with cognitive impairment and increases risk of incident dementia. However, evidence has been limited on the effect size of depression with cognitive impairment and their synergistic effect on future dementia. To explore this, we examined three large cross-country population-based prospective cohorts. Depressive symptoms were assessed by epidemiologic scale, while cognitive impairment was defined by subjective cognitive tests. Dementia was ascertained by self-reported physician-diagnosed conditions. Cox proportional hazard models were employed to determine the hazard ratio (HR) and 95% confidence interval (95% CI), with adjustments of potential confounding variables. Addictive and multiplicative interactions were calculated to evaluate the synergistic effect. A total of 64,706 participants were included at baseline (mean age: 63.9, female: 55.2%), where 4197 (6.5%) individuals had depressive symptoms only, 28,175 (43.5%) individuals had cognitive impairment only, 11,564 (17.9%) individuals had both, and 20,770 (32.1%) individuals had neither. Compared with the neither group, all the other three groups had higher risks of subsequent dementia (depression only: HR 1.65, 95% CI 1.26–2.17; cognitive impairment only: HR 2.71, 95% CI 2.33–3.14; depression with cognitive impairment: HR 3.51, 95% CI 2.95–4.17). There was insignificant additive (RERI, 0.15, 95% CI −0.45–0.75; AP, 0.042, 95% CI −0.13–0.21; SI, 1.06, 95% CI 0.83–1.37) and multiplicative (0.78, 95% CI 0.58–1.06) interaction between depression and cognitive impairment on subsequent dementia. We found depression with cognitive impairment has higher risks of dementia than either condition alone and no significant synergistic effect exists between these two factors.

Background: Allergic asthma is largely dominated by Th2 lymphocytes. Micropeptides in Th2 cells and asthma remain unmasked. Here, we aimed to demonstrate a micropeptide, T-cell regulatory micropeptide (TREMP), in Th2 cell differentiation in asthma. Methods: TREMP translated from lincR-PPP2R5C was validated using Western blotting and mass spectrometry. TREMP knockout mice were generated using CRISPR/Cas9. Coimmunoprecipitation revealed that TREMP targeted pyrroline-5-carboxylate reductase 1 (PYCR1), which was further explored in vitro and in vivo. The levels of TREMP and PYCR1 in Th2 cells from clinical samples were determined by flow cytometry. Results: TREMP, encoded by lincR-PPP2R5C, was in the mitochondrion. The lentivirus encoding TREMP promoted Th2 cell differentiation. In contrast, Th2 differentiation was suppressed in TREMP−/− CD4+ T cells. In the HDM-induced model of allergic airway inflammation, TREMP was increased in pulmonary tissues. Allergic airway inflammation was relieved in TREMP−/− mice treated with HDM. Mechanistically, TREMP interacted with PYCR1, which regulated Th2 differentiation via glycolysis. Glycolysis was decreased in Th2 cells from TREMP−/− mice and PYCR1−/− mice. Similar to TREMP−/− mice, allergic airway inflammation was mitigated in HDM-challenged PYCR1−/− mice. Moreover, we measured TREMP and PYCR1 in asthma patients. And we found that, compared with those in healthy controls, the levels of TREMP and PYCR1 in Th2 cells were significantly increased in asthmatic patients. Conclusions: The micropeptide TREMP encoded by lincR-PPP2R5C promoted Th2 differentiation in allergic airway inflammation by interacting with PYCR1 and enhancing glycolysis. Our findings highlight the importance of neglected micropeptides from noncoding RNAs in allergic diseases.

Persistence of quiescent leukemia stem cells (LSCs) after treatment most likely contributes to chemotherapy resistance and poor prognosis of leukemia patients. Identification of this quiescent cell population would facilitate eradicating LSCs. Here, using a cell‐tracing PKH26 (PKH) dye that can be equally distributed to daughter cells following cell division in vivo, we identify a label‐retaining slow‐cycling leukemia cell population from AML1‐ETO9a (AE9a) leukemic mice. We find that, compared with cells not maintaining PKH‐staining, a higher proportion of PKH‐retaining cells are in G0 phase, and PKH‐retaining cells exhibit increased colony formation ability and leukemia initiation potential. In addition, PKH‐retaining cells possess high chemo‐resistance and are more likely to be localized to the endosteal bone marrow region. Based on the transcriptional signature, HLA class II histocompatibility antigen gamma chain (Cd74) is highly expressed in PKH‐retaining leukemia cells. Furthermore, cell surface CD74 was identified to be highly expressed in LSCs of AE9a mice and CD34+ human leukemia cells. Compared to Lin−CD74− leukemia cells, Lin−CD74+ leukemia cells of AE9a mice exhibit higher stemness properties. Collectively, our findings reveal that the identified slow‐cycling leukemia cell population represents an LSC population, and CD74+ leukemia cells possess stemness properties, suggesting that CD74 is a candidate LSC surface marker.

Abstract Immune checkpoint inhibitors (ICIs) immunotherapy facilitates new approaches to achieve precision cancer treatment. A growing number of patients with non-small cell lung cancer (NSCLC) have benefited from treatment with neoadjuvant ICIs combined with chemotherapy. However, the mechanisms and associations between the therapeutic efficacy of neoadjuvant pembrolizumab and chemotherapy (NAPC) and macrophage subsets are still unclear. We performed single-cell RNA sequencing (scRNA-seq) and identified a novel FABP4+C1q+ macrophage subtype, which exhibited stronger proinflammatory cytokine production and phagocytic ability. This subtype was found to be more abundant in tumor tissues and lymph nodes of major pathological response (MPR) patients compared to non-MPR patients, and was associated with a good efficacy of NAPC. Multiplex fluorescent immunohistochemical (mIHC) staining was subsequently used to verify our findings. Further mechanistic studies indicated that FABP4 and C1q regulate the expression of proinflammatory cytokines synergistically. In addition, FABP4 and C1q promote fatty acid synthesis, enhance anti-apoptosis ability and phagocytic ability of macrophage via the interaction of AMPK/JAK/STAT axis. This study provides novel insights into the underlying mechanisms and predictive biomarkers of NAPC. Our findings contribute to improving the prognosis of patients with NSCLC by potentially guiding more precise patient selection and treatment strategies. Novelty & Impact Statements We identified a group of macrophages (FABP4+C1q+ macrophages) related to the therapeutic efficacy of neoadjuvant chemoimmunotherapy. FABP4+C1q+ macrophages highly expressed proinflammatory cytokines-related genes and had a strong cytokine production and phagocytic ability. We believe that our study provides a novel insight into the synergistic mechanism of neoadjuvant ICI combined with chemotherapy and may lead to improved clinical outcomes in patients with NSCLC in the future.

Abstract Aiming at the problem of sub‐synchronous oscillations induced by direct‐drive wind farms with series‐compensated lines, this paper proposes an unknown system dynamics estimation‐based PI controller to achieve sub‐synchronous oscillation suppression. According to the mathematical model of the direct‐drive wind farm grid‐connected system, the relationship between the direct‐drive wind turbine grid‐side converter current inner‐loop PI controller and the sub‐synchronous components is first established. Secondly, the uncertain sub‐synchronous current components and voltage components in the series‐compensated lines of the direct‐drive wind farm are taken as the total disturbance, and an unknown system dynamic estimator‐based PI controller is designed by introducing the first‐order low‐pass filter operation. Then, the stability and convergence of the closed‐loop system are proved by Lyapunov theory. Finally, the Prony method is used to analyse the current signal output by the direct‐drive wind turbine, and the inherent characteristics of the negative damping of the SSO induced by the series‐compensated line of the direct‐driven wind farm are revealed. A comparative numerical simulation is carried out to demonstrate that the sub‐synchronous oscillations of the direct‐drive wind farm with series‐compensated lines can be suppressed under different operating conditions.

Abstract Insulator defect detection is a critical aspect of grid inspection in reality, yet it faces intricate environmental challenges, such as slow detection speed and low accuracy. To address this issue, we propose a YOLOv8-based insulator defect detection algorithm named CDDCR–YOLOv8. This algorithm divides the input insulator images into multiple grid cells, with each grid cell responsible for predicting the presence and positional information of one or more targets. First, we introduce the Coordinate Attention (CA) mechanism module into the backbone network and replace the original C2f module with the enhanced C2f_DCN module. Second, improvements are made to the original upsampling and downsampling layers in the neck network, along with the introduction of the lightweight module RepGhost. Finally, we employ Wise-IoU (WIoU) to replace the original CIoU as the loss function for network regression. Experimental results demonstrate that the improved algorithm achieves an average precision mean (mAP @ 0.5) of 97.5% and 90.6% on the CPLID and IPLID data sets, respectively, with a frame per second (FPS) of 84, achieving comprehensive synchronous improvement. Compared to traditional algorithms, our algorithm exhibits significant performance enhancement.

Abstract The aim of this study was to examine the effect of a positive emotion‐based exercise intervention on quality of life (QOL), fatigue, and mental health status in patients with lung cancer undergoing chemotherapy. A total of 80 patients with lung cancer undergoing chemotherapy were selected and divided into an observation group and a control group, with 40 patients in each group. Patients in the control group received routine care and were educated about the benefits of exercise, while patients in the experimental group received an additional exercise intervention based on positive emotions. We assessed patients' quality of life, fatigue, and mental health at the time of recruitment and 12 weeks after the exercise intervention. After the intervention, patients in the experimental group had a higher overall QOL score than those in the control group, with statistically significant differences in body, role, and emotions (p

Abstract Cavity optomechanical systems have enabled precision sensing of magnetic fields, by leveraging the optical resonance-enhanced readout and mechanical resonance-enhanced response. Previous studies have successfully achieved mass-produced and reproducible microcavity optomechanical magnetometry (MCOM) by incorporating Terfenol-D thin films into high-quality (Q) factor whispering gallery mode (WGM) microcavities. However, the sensitivity was limited to 585 pT Hz−1/2, over 20 times inferior to those using Terfenol-D particles. In this work, we propose and demonstrate a high-sensitivity and mass-produced MCOM approach by sputtering a FeGaB thin film onto a high-Q SiO2 WGM microdisk. Theoretical studies are conducted to explore the magnetic actuation constant and noise-limited sensitivity by varying the parameters of the FeGaB film and SiO2 microdisk. Multiple magnetometers with different radii are fabricated and characterized. By utilizing a microdisk with a radius of 355 μm and a thickness of 1 μm, along with a FeGaB film with a radius of 330 μm and a thickness of 1.3 μm, we have achieved a remarkable peak sensitivity of 1.68 pT Hz−1/2 at 9.52 MHz. This represents a significant improvement of over two orders of magnitude compared with previous studies employing sputtered Terfenol-D film. Notably, the magnetometer operates without a bias magnetic field, thanks to the remarkable soft magnetic properties of the FeGaB film. Furthermore, as a proof of concept, we have demonstrated the real-time measurement of a pulsed magnetic field simulating the corona current in a high-voltage transmission line using our developed magnetometer. These high-sensitivity magnetometers hold great potential for various applications, such as magnetic induction tomography and corona current monitoring.

Abstract Background Unhealthy lifestyles, which include unhealthy diet and unhealthy sleep duration, have been widely recognized as modifiable risk factors for depressive symptoms. This study aims to explore the associations between dietary quality, sleep duration, and depression symptoms, as well as their combined effects. Methods The NHANES 2007 to 2014 cycles provided the data for this study, in which 19,134 adults aged 20 years and older were included. Unhealthy diet, measured using an average Healthy Eating Index (HEI)-2015 score below the 60th percentile, and unhealthy sleep duration, measured as sleep duration at night less than 7 h or greater than/equal to 9 h, were the primary exposures. Then participants were divided into four different lifestyles. A weighted-multivariable logistic regression was employed, controlling for relevant variables. Furthermore, stratified analyses were conducted to assess the robustness of the findings and identify potential high-risk groups. Results The overall prevalence of depressive symptoms among all participants was 8.44%. Among the participants, 56.58% met the criteria for healthy sleep duration, and 24.83% scored at or above the 60th percentile on the HEI-2015. Unhealthy diet (OR: 1.40, 95% CI: 1.18–1.67, p

Abstract Background Medical fear is a common psychological reaction in hospitalized children, especially during radiotherapy for central nervous system (CNS) cancers. This fear not only causes negative emotions such as anxiety and depression but also affects children’s quality of life and treatment outcomes. It is exacerbated by factors such as unfamiliar environments during radiation therapy and separation from parents. Child Life, as a professional service, offers physical and mental support to children through medical understanding and psychological preparation, addressing their social and psychological needs, among other things. This study aims to construct a comprehensive Child Life intervention program (CCLIP), consisting of four key components: psychological adjustment and preparation, therapeutic play, pain management and coping strategies, and family support. The integration of effective intervention methods aims to reduce medical fear in children undergoing radiotherapy, promote psychological well-being, improve treatment compliance, and enhance quality of life. Methods This study is a protocol for a randomized controlled trial. Using a random number table method, we plan to recruit 38 eligible children who meet the inclusion criteria and then randomize them into two distinct groups: the intervention group and the control group. The intervention group will receive the CCLIP, and the control group will receive standardized care. Data will be collected through questionnaires and on-site assessments during the one-month intervention period at four distinct time points: the day of admission (T0), the first radiotherapy positioning (T1), mid-radiotherapy (T2), and postradiotherapy (T3). The primary outcome measure is the effectiveness of the CCLIP in reducing medical fear among children receiving radiation treatment for CNS cancers. Secondary outcomes include anxiety, depression, radiation adherence, quality of life among children, and parental satisfaction. Discussion This study aims to alleviate medical fear among children with CNS tumors undergoing radiotherapy through the implementation of the CCLIP while enhancing their mental health and quality of life. The expected outcomes of this research include providing effective intervention strategies for clinical practice, improving the treatment experience and long-term prognosis of children, and having positive impacts on children and their families. Trial registration This study is registered at the Chinese Clinical Trial Registry, ChiCTR2400082622. Registered 2 April, 2024.

Compacted clay liners are extensively used as barriers to control the upward diffusion of vapors of volatile or semi-volatile organic contaminants released from unsaturated contaminated soils at industry-contaminated sites. This study aimed to investigate the gas diffusion barrier performance of compacted clayey soils amended with three agents including attapulgite and diatomite individually, and attapulgite/diatomite mixture. The properties including water retention, volumetric shrinkage, gas diffusion, and unconfined compressive strength were evaluated through a series of laboratory tests of amended compacted clayey soils. The results demonstrate that the decrease in volume proportions of inter-aggregate pores leads to an increase in unconfined compressive strength (qu). Both hydrophilic groups and microstructures of attapulgite and diatomite result in an increase in water retention percent (Wt) of compacted clayey soil specimens after amendment regardless of the type of agent or initial water content (w0). Furthermore, the ratio of the gas diffusion coefficient (De) to the gas diffusion coefficient in the air (Da) was significantly reduced owing to a decrease in volume proportions of inter-aggregate pores, hydrophilic group, and microstructures of attapulgite and diatomite. Scanning electron microscope analyses revealed that rod-shaped attapulgite filled the inter-aggregate pores formed by clay particles, whereas the disc-shaped diatomite particles, characterized by micropores, failed to obstruct the inter-aggregate pores due to their larger particle size. Mercury intrusion porosimetry (MIP) analyses showed a reduction in pore volume in the inter-aggregate pores, leading to a reduction in the total pore volume for both the attapulgite and attapulgite/diatomite mixture amended clays, which is in accordance with the scanning electron microscope (SEM) results. The findings are pertinent to the practical application of compacted clay liners as gas barriers against the upward migration of volatile or semi-volatile organic contaminants at contaminated sites.

Abstract Background Hepatic progenitor cells serve not only as the origin of combined hepatocellular cholangiocarcinoma (cHCC-CCA) but are also responsible for malignancy recurrence after surgical resection. Nucleophosmin 1 (NPM1) has been implicated in cancer metastasis and poor prognosis. This study aimed to determine the expression of NPM1 by hepatic progenitor cells in cHCC-CCA and the effects of targeting NPM1 on hepatic progenitor cells and BEL-7402 cells with characteristics of both progenitor cells and cHCC-CCA. Methods First, NPM1 was detected by RT‒PCR, western blotting, and double-immunofluorescence staining in cHCC-CCA tissues. NPM1 expression was subsequently analysed in rat hepatic progenitor cells cultured in vitro and in interleukin 6 (IL6)-treated cells. The effects and mechanism of NPM1 on hepatic progenitor cells were determined by knocking down NPM1 and performing RNA sequencing analysis. Finally, NSC348884, a small-molecule inhibitor that disrupts NPM1 dimer formation, was used to confirm the function of NPM1 in BEL-7402 cells. Results Both human hepatic progenitor cells in cHCC-CCA tissues and rat in vitro cultured hepatic progenitor cells highly expressed NPM1. IL6, a cytokine involved in the malignant transformation of hepatic progenitor cells, dose-dependently increased NPM1 and PCNA expression. Knocking down NPM1 reduced IL6R transcription (P

Abstract This study aims to evaluate the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker for cardiovascular mortality among cancer patients, utilizing data from the National Health and Nutrition Examination Survey (NHANES). From the NHANES dataset (2007–2018), we analyzed 4974 cancer survivors, investigating the prognostic significance of NLR for all-cause, cardiovascular, and cancer-specific mortality. Survival outcomes were analyzed using Cox regression and Kaplan–Meier methods. Optimal NLR cutoffs were identified as 2.61 for differentiating the higher NLR group from lower NLR group. Elevated NLR levels significantly correlated with increased all-cause mortality (HR 1.11, 95% CI 1.07–1.14, P

Abstract Background Seven-carbon sugars, which rarely exist in nature, are the key constitutional unit of septacidin and hygromycin B in bacteria. These sugars exhibit a potential therapeutic effect for hypoglycaemia and cancer and serve as building blocks for the synthesis of C-glycosides and novel antibiotics. However, chemical and enzymatic approaches for the synthesis of seven-carbon sugars have faced challenges, such as complex reaction steps, low overall yields and high-cost feedstock, limiting their industrial-scale production. Results In this work, we propose a strain engineering approach for synthesising sedoheptulose using glucose as sole feedstock. The gene pfkA encoding 6-phosphofructokinase in Corynebacterium glutamicum was inactivated to direct the carbon flux towards the pentose phosphate pathway in the cellular metabolic network. This genetic modification successfully enabled the synthesis of sedoheptulose from glucose. Additionally, we identified key enzymes responsible for product formation through transcriptome analysis, and their corresponding genes were overexpressed, resulting in a further 20% increase in sedoheptulose production. Conclusion We achieved a sedoheptulose concentration of 24 g/L with a yield of 0.4 g/g glucose in a 1 L fermenter, marking the highest value up to date. The produced sedoheptulose could further function as feedstock for synthesising structural seven-carbon sugars through coupling with enzymatic isomerisation, epimerisation and reduction reactions.

Abstract Besides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing. Based on the STARTRAC-like algorithm, we defined bystander T cells and tumor-reactive T cells. Compared with bystander T cells, tumor-reactive T cells presented as senescent-like cytotoxic terminally differentiated T cells (Temra) with upregulated NK-related markers. Additionally, we found ADGRG1 could serve as the specific marker of CD8+ T tumor-reactive T cell and validated it through the Runx1Runx1t1/+; Mx1-Cre mouse model. In chimeric antigen receptor (CAR)-T and target cell system, ADGRG1 was selectively upregulated upon antigen-TCR encounter. Moreover, ADGRG1+CD8+ T cells released a higher level of IFN-γ and showed higher cell-killing ability when exposed to matched AML blasts. Together, our findings depict the single-cell profile of tumor-reactive T cells in AML BM and propose that ADGRG1 can act as an indicator of T cell tumor reactivity in AML, which may be further harnessed for adoptive cell therapy and tumor-reactive TCR enrichment.

Soliton microcombs, which require the hosting cavity to operate in an anomalous dispersion regime, are essential to integrate photonic systems. In the past, soliton microcombs were generated on cavity whispering gallery modes (WGMs), and the anomalous dispersion requirement of the cavity made by normal dispersion material was achieved through structural dispersion engineering. This inevitably degrades the cavity optical quality factor (Q) and increases pump threshold power for soliton comb generation. To overcome the challenges, here, we report a soliton microcomb excited by cavity polygon modes. These modes display anomalous dispersion at near-infrared while optical Q factors exceeding 4×106 are maintained. Consequently, a soliton comb spanning from 1450 nm to 1620 nm with a record low pump power of 11 mW is demonstrated, a three-fold improvement compared to the state of the art on the same material platform.

Abstract Since October 2023, a significant outbreak of Mycoplasma Pneumoniae Pneumonia (MPP) has been observed in children in northern China. Chinese health authorities have attributed this epidemiological to immune debt resulting from the relaxation of coronavirus disease 2019 (COVID-19) control measures. This study described the epidemiological features of Mycoplasma pneumoniae (MP) prevalence in children and developed a straightforward prediction model to differentiate between MPP and viral pneumonia in children. The infection rate of MP in children notably increased from 8.12 in 2022 to 14.94% in 2023, peaking between October and November, especially among school-age children. Logistic regression screening identified four key indicators: Age, D-Dimer levels, erythrocyte sedimentation rate, and gender. The developed nomogram exhibited a receiver operator characteristic curve-area under the curve (ROC-AUC) of 0.858, with external validation confirming an ROC-AUC of 0.794. This study examined the epidemiological characteristics of MPP prevalence in children in Shandong Province during and after the COVID-19 pandemic. An early predict model was developed and validated to differentiate between Mycoplasma Pneumoniae and viral infections.

Abstract The spatial delays of pulmonary tuberculosis (PTB) have been less explored. In this study, a total of 151,799 notified PTB cases were included, with median patient and diagnostic delays of 15 [interquartile range (IOR), 4–35] and 2 (IOR, 0–8) days, respectively. The spatial autocorrelation analysis and spatial–temporal scan statistics were used to determine the clusters, indicating that the regions in the southwestern and northeastern parts of Zhejiang Province exhibited high rates of long-term patient delay (LPD, delay ≥ 15 days) and long-term diagnostic delay (LDD, delay ≥ 2 days). Besides, the Mantel test indicated a moderately positive correlation between public awareness of suspicious symptoms and the LPD rate in 2018 (Mantel's r = 0.4, P

Abstract During follicular development, changes in the composition of the follicular fluid are synchronized with the development of oocytes. Our aim was to screen the key factors affecting oocyte maturation and optimize the in vitro culture protocol by understanding the changes of proteins and metabolites in follicular fluid. Follicles are divided into three groups according to their diameter (small follicle fluid (SFF): 10 mm

Abstract The rheological parameters of oil testing fluids play a crucial role in safely conducting oil testing operations, protecting reservoirs, and maintaining wellbore integrity, which are greatly influenced by temperature and pressure. This article conducted rheological experiments on commonly used potassium salt polymer systems and organic salt systems for oil testing fluids in the Bohai Bay Oilfield under 4–200 °C and 30–150 MPa. The experiments revealed the variation of rheological parameters with temperature and pressure. Nine commonly used rheological models were evaluated for their applicability to the two types of oil testing fluids. It was found that the Ross model was suitable for the potassium salt polymer system, while the power-law model was suitable for organic salt oil testing fluids. A new rheological parameter prediction model suitable for wide range of temperature and pressure and different testing fluid systems was proposed based on the optimized results. The average error for the potassium salt polymer system for oil testing fluids was 0.101%, and the error for the organic salt system for oil testing fluids was 0.113%. Both were superior to known rheological models and can meet the requirements of oil testing operations within the wide temperature and pressure range in the Bohai Bay Oilfield.

Abstract Objective Bibliometrics was employed in this study to determine the research trends in the worldwide application of 3D printing technology to treat bone tumors over the previous 10 years. Methods Published from 2013 to 2022, the papers related to bone tumors treated with 3D printing were located in Web of Science Core Collection (WoSCC), PubMed, and Scopus. The screened articles were included in this bibliometric study. From these papers in WoSCC, information on annual publications, journals, keywords, countries, authors, institutions, and cited references were extracted and visualized with CiteSpace (version 6.1.R6) software to investigate the state of bone tumor treatment using 3D printing as well as research hotspots. The Carrot2 online visualization tool and Vosviewer software (version 1.6.20) were employed to visualize the publications from PubMed and Scopus, respectively, in order to ascertain the most popular research topics from both databases. Results A total of 606, 233, and 364 publications were obtained from WoSCC, PubMed, and Scopus, respectively, between the years 2013 and 2022. In WoSCC, the peak number of publications was found in 2021, with 145 publications published. Acta Biomaterialia (11 publications) and World Neurosurgery (10 publications) were the most prolific journals, and Biomaterials was the journal cited the most (244 times). Yong Zhou was the most productive author with 14 publications, while Kwok-Chuen Wong (69 citations) and William F Enneking, (69 citations) possessed the most citations. The country with the largest quantity of publications was China (207). Among all institutions, Shanghai Jiao Tong University produced the most publications (29). Rapid prototyping was the keyword with the strongest citation burst (4.73). ‘Reconstruction’, ‘surgery’, ‘resection’, and ‘design’ caught the significant attention of researchers. 3D-printed materials, pelvic reconstruction, mandibular reconstruction, computer-assisted surgical techniques, photothermal therapy, and in vitro experiments were recognized as hot subjects and trends in current research. The most frequently occurring topics in Scopus are not significantly different from those found in WoSCC. The most prevalent research areas in PubMed encompass implant, patient-specific, bioceramic, models, and pelvic.

Abstract Sustainable photoactivated room temperature phosphorescent materials exhibit great potential but are difficult to obtain. Here, we develop photoactivated room temperature phosphorescent materials by covalently attaching lignin to polylactic acid, where lignin and polylactic acid are the chromophore and matrix, respectively. Initially the phosphorescence of the lignin is quenched by residual O2. However, the phosphorescence is switched on when the residual oxygen is consumed by the triplet excitons of lignin under continuous UV light irradiation. As such, the lifetime increases from 3.0 ms to 221.1 ms after 20 s of UV activation. Interestingly, the phosphorescence is quenched again after being kept under an atmosphere of air for 2 h in the absence of UV irradiation due to the diffusion of oxygen into the materials. Using these properties, as-developed material is successfully used as a smart anti-counterfeiting logo for a medicine bottle and for information recording.

Abstract Background Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. Results Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3′-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain‐of‐function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. Conclusions These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.

Abstract Background Ischemic stroke (IS) is a major cause of death and disability worldwide. Genetic factors are important risk factors for the development of IS. The quinone oxidoreductase 1 gene (NQO1) has antioxidant, anti-inflammatory, and cytoprotective properties. Thus, in this study, we investigated the relationship between NQO1 gene polymorphism and the risk of IS. Methods Peripheral blood was collected from 143 patients with IS and 124 the control groups in Yunnan, China, and NQO1 rs2917673, rs689455, and rs1800566 were genotyped. Logistic regression was used to analyze the relationship between the three NQO1 loci and IS susceptibility. The difference in the expression levels of NQO1 between the control groups and IS groups was verified using public databases and enzyme-linked immunosorbent assay. Results The rs2917673 locus increased the risk of IS by 2.375 times in TT genotype carriers under the co-dominance model compared with CC carriers and was statistically associated with the risk of IS (OR = 2.375, 95% CI = 1.017–5.546, P = 0.046). In the recessive model, TT genotype carriers increased IS risk by 2.407 times compared with CC/CT carriers and were statistically associated with the risk of IS (OR = 2.407, 95% CI = 1.073–5.396, P = 0.033). Conclusions NQO1 rs2917673 polymorphism is significantly associated with IS. Mutant TT carriers are risk factors for IS.

Abstract Purpose To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity. Methods The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB). Results Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P

Abstract Objectives To evaluate the diagnostic accuracy of liver dual-layer spectral-detector CT (SDCT) derived parameters of liver parenchyma for grading steatosis with reference to magnetic resonance imaging-based proton density fat fraction (MRI-PDFF). Methods Altogether, 320 consecutive subjects who underwent MRI-PDFF and liver SDCT examinations were recruited and prospectively enrolled from four Chinese hospital centers. Participants were classified into normal (n = 152), mild steatosis (n = 110), and moderate/severe(mod/sev) steatosis (n = 58) groups based on MRI-PDFF. SDCT liver parameters were evaluated using conventional polychromatic CT images (CTpoly), virtual mono-energetic images at 40 keV (CT40kev), the slope of the spectral attenuation curve (λ), the effective atomic number (Zeff), and liver to spleen attenuation ratio (L/S ratio). Linearity between SDCT liver parameters and MRI-PDFF was examined using Spearman correlation. Cutoff values for SDCT liver parameters in determining steatosis grades were identified using the area under the receiver-operating characteristic curve analyses. Results SDCT liver parameters demonstrated a strong correlation with PDFF, particularly Zeff (rs = −0.856; p

Abstract Background Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. Methods We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. Results The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. Conclusions This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Abstract Background Aging is a multifaceted process that affects all organ systems. With the increasing trend of population aging, aging-related diseases have resulted in significant medical challenges and socioeconomic burdens. Mesenchymal stromal cells (MSCs), due to their antioxidative stress, immunoregulatory, and tissue repair capabilities, hold promise as a potential anti-aging intervention. Methods In this study, we transplanted MSCs into naturally aged rats at 24 months, and subsequently examined levels of aging-related factors such as β-galactosidase, superoxide dismutase, p16, p21 and malondialdehyde in multiple organs. Additionally, we assessed various aging-related phenotypes in these aged rats, including immune senescence, lipid deposition, myocardial fibrosis, and tissue damage. We also conducted a 16 S ribosomal ribonucleic acid (rRNA) analysis to study the composition of gut microbiota. Results The results indicated that MSCs significantly reduced the levels of aging-associated and oxidative stress-related factors in multiple organs such as the heart, liver, and lungs of naturally aging rats. Furthermore, they mitigated chronic tissue damage and inflammation caused by aging, reduced levels of liver lipid deposition and myocardial fibrosis, alleviated aging-associated immunodeficiency and immune cell apoptosis, and positively influenced the gut microbiota composition towards a more youthful state. This research underscores the diverse anti-aging effects of MSCs, including oxidative stress reduction, tissue repair, metabolic regulation, and improvement of immune functions, shedding light on the underlying anti-aging mechanisms associated with MSCs. Conclusions The study confirms that MSCs hold great promise as a potential anti-aging approach, offering the possibility of extending lifespan and improving the quality of life in the elderly population.