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Abstract The “gut-brain axis” is involved in many physiological processes. However, its role in regulating mammary gland (MG) development remains unknown. In this study, we established the mice model of bilateral subdiaphragmatic vagotomy (Vago) to clarify the effects of “gut-brain axis” on MG development in pubertal mice. The results showed that Vago reduced the ratio of Lactobacillus and Bifidobacterium, neuronal excitability in the nucleus of solitary tract (NTS), and synthesis and secretion of BDNF, thereby slowing MG development. Transplanting the gut microbiota of Vago mice to recipient mice replicated these effects, and transplanting the gut microbiota of Control mice to Vago mice did not alleviate these effects. Galacto-Oligosaccharide (GOS), which up-regulates the ratio of Lactobacillus and Bifidobacterium, supplementation elevated NTS neuron excitability, synthesis and secretion of BDNF, and MG development, but Vago reversed these benefits. In conclusion, GOS enhances BDNF-mediated mammary gland development in pubertal mice via the “gut-brain axis”.

Abstract Background Diabetic cardiomyopathy (DCM) is a serious complication in patients with type 2 diabetes mellitus, and its mechanisms are complex and poorly understood. Despite growing evidence suggesting that ferroptosis plays a significant role in cardiovascular disease, it has been less extensively studied in DCM. Fibroblast growth factor 21 (FGF21), whose mechanism of action is closely related to ferroptosis, is widely utilized in studies focused on the prevention and treatment of glucolipid metabolism-related diseases and cardiovascular diseases. Objective To confirm the significant role of ferroptosis in DCM and to investigate whether FGF21 improves DCM by inhibiting ferroptosis and elucidating its specific molecular mechanisms. Methods The animal DCM models were established through high-fat feeding combined with streptozotocin injection in C57BL/6J mice or by db/db mice, and the diabetic cardiomyocyte injury model was created using high glucose and high fat (HG/HF) culture of primary cardiomyocytes. Intervention modeling of FGF21 were performed by injecting adeno-associated virus 9-FGF21 in mice and transfecting FGF21 siRNA or overexpression plasmid in primary cardiomyocytes. Results The findings indicated that ferroptosis was exacerbated and played a significant role in DCM. The overexpression of FGF21 inhibited ferroptosis and improved cardiac injury and function, whereas the knockdown of FGF21 aggravated ferroptosis and cardiac injury and function in DCM. Furthermore, we discovered that FGF21 inhibited ferroptosis in DCM by directly acting on ferritin and prolonging its half-life. Specifically, FGF21 binded to the heavy and light chains of ferritin, thereby reducing its excessive degradation in the proteasome and lysosomal-autophagy pathways in DCM. Additionally, activating transcription factor 4 (ATF4) served as the upstream regulator of FGF21 in DCM. Conclusions The ATF4-FGF21-ferritin axis mediates the protective effects in DCM through the ferroptosis pathway and represents a potential therapeutic target for DCM.

To understand the strengths of rocks under complex stress states, a generalized nonlinear three-dimensional (3D) Hoek‒Brown failure (NGHB) criterion was proposed in this study. This criterion shares the same parameters with the generalized HB (GHB) criterion and inherits the parameter advantages of GHB. Two new parameters, β, and n, were introduced into the NGHB criterion that primarily controls the deviatoric plane shape of the NGHB criterion under triaxial tension and compression, respectively. The NGHB criterion can consider the influence of intermediate principal stress (IPS), where the deviatoric plane shape satisfies the smoothness requirements, while the HB criterion not. This criterion can degenerate into the two modified 3D HB criteria, the Priest criterion under triaxial compression condition and the HB criterion under triaxial compression and tension condition. This criterion was verified using true triaxial test data for different parameters, six types of rocks, and two kinds of in situ rock masses. For comparison, three existing 3D HB criteria were selected for performance comparison research. The result showed that the NGHB criterion gave better prediction performance than other criteria. The prediction errors of the strength of six types of rocks and two kinds of in situ rock masses were in the range of 2.0724%–3.5091% and 1.0144%–3.2321%, respectively. The proposed criterion lays a preliminary theoretical foundation for prediction of engineering rock mass strength under complex in situ stress conditions.

Patient-derived tumor organoids (PDTOs) shows great potential as a preclinical model. However, the current methods for establishing PDTOs primarily focus on modulating local properties, such as sub-micrometer topographies. Nevertheless, they neglect to capture the global millimeter or intermediate mesoscale architecture that have been demonstrated to influence tumor response to therapeutic treatment and tumor progression. In this study, we present a rapid technique for generating collagen bundles with an average length of 90 ± 27 μm and a mean diameter of 5 ± 1.5 μm from tumor tissue debris that underwent mechanical agitation following enzymatic digestion. The collagen bundles were subsequently utilized for the fabrication of biomimetic hydrogels, incorporating microbial transglutaminase (mTG) crosslinked gelatin. These biomimetic hydrogels, referred to as MC-gel, were specifically designed for patient-derived tumor organoids. The lung cancer organoids cultured in MC-gel exhibited larger diameters and higher cell viability compared to those cultured in gels lacking the mesoscale collagen bundle; moreover, their irregular morphology more closely resembled that observed in vivo. The MC-gel-based lung cancer organoids effectively replicated the histology and mutational landscapes observed in the original donor patient’s tumor tissue. Additionally, these lung cancer organoids showed a remarkable similarity in their gene expression and drug response across different matrices. This recently developed model holds great potential for investigating the occurrence, progression, metastasis, and management of tumors, thereby offering opportunities for personalized medicine and customized treatment options.

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are pulmonary conditions that cause significant morbidity and mortality. The common etiologies of these conditions include pneumonia, pulmonary contusion, fat embolism, smoke inhalation, sepsis, shock, and acute pancreatitis. Inflammation, oxidative stress, apoptosis, and autophagy are key pathophysiological mechanisms underlying ALI. Hydrogen sulfide (H2S) and sulfur dioxide (SO2) are sulfur-containing gas signaling molecules that can mitigate these pathogenic processes by modulating various signaling pathways, such as toll-like receptor 4 (TLR4)/nod-like receptor protein 3 (NLRP3), extracellular signal-regulating protein kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK), phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), and nuclear factor kappa B (NF-κB), thereby conferring protection against ALI. Given the limited clinical effectiveness of prevailing ALI treatments, investigation of the modulation of sulfur-containing gas signaling molecules (H2S and SO2) in ALI is imperative. This article presents an overview of the regulatory pathways of sulfur-containing gas signaling molecules in ALI animal models induced by various stimuli, such as lipopolysaccharide, gas inhalation, oleic acid, and ischemia-reperfusion. Furthermore, this study explored the therapeutic prospects of diverse H2S and SO2 donors for ALI, stemming from diverse etiologies. The aim of the present study was to establish a theoretical framework, in order to promote the new treatment of ALI.

Abstract While protein aggregation’s association with aging and age-related diseases is well-established, the specific proteins involved and whether dissolving them could alleviate aging remain unclear. Our research addresses this gap by uncovering the role of PKM2 aggregates in aging. We find that PKM2 forms aggregates in senescent cells and organs from aged mice, impairing its enzymatic activity and glycolytic flux, thereby driving cells into senescence. Through a rigorous two-step small molecule library screening, we identify two compounds, K35 and its analog K27, capable of dissolving PKM2 aggregates and alleviating senescence. Further experiments show that treatment with K35 and K27 not only alleviate aging-associated signatures but also extend the lifespan of naturally and prematurely aged mice. These findings provide compelling evidence for the involvement of PKM2 aggregates in inducing cellular senescence and aging phenotypes, and suggest that targeting these aggregates could be a promising strategy for anti-aging drug discovery.

Abstract Empathy enables understanding and sharing of others’ feelings. Human neuroimaging studies have identified critical brain regions supporting empathy for pain, including the anterior insula (AI), anterior cingulate (ACC), amygdala, and inferior frontal gyrus (IFG). However, to date, the precise spatio-temporal profiles of empathic neural responses and inter-regional communications remain elusive. Here, using intracranial electroencephalography, we investigated electrophysiological signatures of vicarious pain perception. Others’ pain perception induced early increases in high-gamma activity in IFG, beta power increases in ACC, but decreased beta power in AI and amygdala. Vicarious pain perception also altered the beta-band-coordinated coupling between ACC, AI, and amygdala, as well as increased modulation of IFG high-gamma amplitudes by beta phases of amygdala/AI/ACC. We identified a necessary combination of neural features for decoding vicarious pain perception. These spatio-temporally specific regional activities and inter-regional interactions within the empathy network suggest a neurodynamic model of human pain empathy.

ObjectiveExplore the application effects of “Internet +” continuous emotional management training in depression patients and analyze the feasibility of innovative rehabilitation training methods.MethodsConveniently selected 100 discharged patients meeting the diagnostic criteria for depression from the Second Affiliated Hospital of Xinxiang Medical University between August 2022 and January 2023 as study subjects. They were divided into an intervention group and a control group according to their discharge time, with 50 patients in each group. The control group received routine monthly telephone follow-ups and “Internet +” health popularization. The intervention group received “Internet +” continuous emotional management training in addition to the control group’s protocol. Before and after the intervention, the Hamilton Depression Rating Scale (HAMD), the Chinese version of the Cognitive Emotion Regulation Questionnaire (CERQ-C), and the Social Adaptation Function Evaluation Scale (SAFE) were used to compare the differences in depression relief, cognitive emotion regulation levels, and social functions between the two groups.ResultsTwo patients in the control group and three patients in the intervention group were lost to follow-up during the intervention, Ultimately, 48 patients in the control group and 47 patients in the intervention group completed the study. Before the intervention, there were no statistically significant differences between the two groups in HAMD scores, CERQ-C subscale scores, and SAFE scores (P < 0.05). After the intervention, the intervention group had significantly lower HAMD and SAFE scores compared to the control group (P < 0.05). In the CERQ-C questionnaire, the intervention group scored lower in self-blame, rumination, catastrophizing, and blaming others but higher in acceptance, positive refocusing, refocusing on planning, positive reappraisal, and putting into perspective compared to the control group, with statistically significant differences (P < 0.05).Conclusion“Internet +” continuity emotion management training can reduce the severity of depression in post-discharge patients and enhance their emotional management and social adaptability. This approach is feasible in clinical practice.

ObjectiveThis study aimed to investigate differences in mind-reading abilities between children with autism and typically developing children across various tasks.MethodsSixteen children with autism (aged 5-8 years) were compared to 16 typically developing children matched in language ability. The unexpected location task and unexpected content task were used to assess implicit and explicit mind-reading abilities using an eye tracker and illustrated storybooks.ResultsFor implicit mind, using differential looking scores shows a no significant difference between the scores of children with autism and typically developing children in the implicit tasks (P=0.399). However, the pupil size show some significant difference between two groups. Second, for the explicit, a significant difference between the scores of children with autism and typically developing children in the explicit tasks (P=0.006). Additionally, only a significant correlation between implicit and explicit mind-reading abilities in children with autism in the unexpected location task was found.ConclusionThe mechanism of implicit mind-reading still not very clear. Pupil-Linked arousal response can be consider as a further tool. Further research on implicit and explicit mind-reading abilities is warranted.

Pathological scars result from abnormal wound healing and represent a fibrotic process in the repair of skin injuries. Post-burn scars are prone to malignant transformation, especially when ulceration occurs, raising concerns for precancerous lesions. We report a case of a 56-year-old female with a 50-year history of a large burn scar on her left forearm. The scar developed non-healing ulceration with local pain and itching over the past three years. Treatment with hematoporphyrin photodynamic therapy (HpD-PDT) led to resolution of the ulceration, thinning of the scar tissue, and significant alleviation of pain and itching. After a five-year follow-up, there has been no recurrence of ulceration, suggesting that photodynamic therapy effectively promotes wound healing in scarred tissue with ulcerations.

ABSTRACT: The relationship between saturated fatty acids (SFA) and bladder cancer (BC) risk has been conflicting. Our aim was to investigate the relationship between erythrocyte membrane SFA and BC risk. A total of 404 participants were enrolled in the study (including 112 cases and 292 controls). A validated food frequency questionnaire was used to assess the food intake. The constitutive composition of fatty acids in the erythrocyte membrane was measured by gas chromatography. After adjustment for BC risk factors, SFA had no significant association with BC risk. However, C18:0 was positively linked with BC risk with an odds ratio (OR; 95% CI) of 2.99 (1.37–6.53). In contrast, very-long-chain saturated fatty acids (VLCSFA), especially C24:0, were negatively related to BC risk with an OR (95% CI) of 0.28 (0.12–0.65) for VLCSFA and 0.33 (0.15–0.75) for C24:0. Higher total odd-chain SFA (C15:0 and C17:0) were associated with a lower risk of BC with OR (95% CI) of 0.18 (0.076–0.44), 0.18 (0.068–0.47), 0.34 (0.14–0.81), respectively. After subgroup analysis, the protective effects C15:0 and C17:0 were still remained. Receiver operating characteristic analysis displayed that the combination of C15:0 and C17:0 indexes increased the accurate predictive rate of BC risk. Further mediation effect analysis showed that C15:0 and C17:0 could be used as partial mediation effectors for milk and dairy products and bladder carcinogenesis. Overall, the combination of odd-chain SFA (C15:0 and C17:0) in the erythrocyte membrane could serve as a reliable mediator and predictor, indicating a relationship between a high intake of milk and dairy products and a lower risk of BC.

Trophic relationships between species in ecosystems are characterized by food webs. However, there is less research on the differences in food web characteristics at larger spatial scales. This study discusses the spatial variations in food web structures across 13 freshwater ecosystems located east of the Hu Line, based on stable isotope techniques. The results show that there are significant spatial differences in the structure of the food web of the studied ecosystem, which is associated with human activities, seasonal variation, environmental factors, etc. Additionally, this study describes how fish exhibit different dietary strategies in response to the fluctuations of food resources, such as the temporal lag of stable isotopic values and changes in trophic ecological niche width (overlap or differentiation). Finally, we summarize the potential uncertainties in the application of stable isotope techniques, emphasizing the necessity to carefully consider these uncertainties when utilizing stable isotope data for ecological research to ensure the accuracy and reliability of the results. The study provides theoretical support for the regional-scale management of freshwater ecosystems.

ABSTRACTPaxilline (PAX) is a tremorgenic mycotoxin that is thought to be associated with various syndromes in animals. To facilitate the determination of this toxin, a hapten was chemically synthesized and then respectively conjugated to Bovine Thyroglobulin (BTG) and Bovine serum albumin (BSA) for antibody production. Monoclonal antibody (mAb) 4F8 was finally obtained and used to establish an accurate and sensitive indirect competitive ELISA (icELISA). Various parameters that could impact the performance of icELISA were optimized, including the ion concentration, pH value and organic solvent. Under optimal condition, this assay exhibits an IC50 value as low as 0.84 µg L−1. The limit of detection (LOD) of the established icELISA method for PAX was 0.03–0.3 µg L−1. In conclusion, this study provided a rapid, sensitive, and high-throughput immunoassay for the detection of PAX in grains.

ABSTRACTThe H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine. Meanwhile, we assessed the relative efficacy of different adjuvants by carrying out a head-to-head comparison of the adjuvants ISA 201 and ISA 71 and evaluated whether the two adjuvants could induce broadly protective immunity. The ISA 71 adjuvanted vaccine induced significantly higher levels of Th1 and Th2 immune responses and provided superior cross-protection against antigenically divergent H5N1 virus challenge than the ISA 201 adjuvanted vaccine. Importantly, increasing the vaccine dose could further enhance the cross-protective efficacy of H5N1 VLP vaccine and confer completely sterilizing protection against antigenically divergent H5N1 virus challenge, which was mediated by neutralizing antibodies. Our results suggest that the H5N1 VLP vaccine can provide broad-spectrum protection against divergent H5N1 influenza viruses as determined by adjuvant and vaccine dose.

Abstract Controlling the growth of bacterial biofilms in a specific pattern greatly enhances the study of cell‐to‐cell interactions and paves the way for expanding their biological applications. However, the development of simple, cost‐effective, and highly resolved biopatterning approaches remains a persistent challenge. Herein, a pioneering photodynamic biopatterning technique for the creation of living bacterial biofilms with customized geometries at high resolutions is presented. First of all, an outstanding aggregation‐induced emission photosensitizer is synthesized to enable efficient photodynamic bacterial killing at a low concentration. By combining with custom‐designed photomasks featuring both opaque and transparent patterns, the viability of photosensitizer‐coated bacteria is successfully manipulated by controlling the degree of light transmittance. This process leads to the formation of living bacterial biofilms with specific patterns replicated from the photomask. Such an innovative strategy can be employed to generate living bacterial biofilms composed of either mono‐ or multispecies, with a spatial resolution of approximately 24 µm. Furthermore, its potential applications in information storage/encryption and antibiotic screening are explored. This study provides an alternative way to understand and investigate the intricate interactions among bacteria within 3D biofilms, holding great promise in the controlled fabrication of dynamic biological systems for advanced applications.

Summary: Bats harbor highly virulent viruses that can infect other mammals, including humans, posing questions about their immune tolerance mechanisms. Bat cells employ multiple strategies to limit virus replication and virus-induced immunopathology, but the coexistence of bats and fatal viruses remains poorly understood. Here, we investigate the antiviral RNA interference pathway in bat cells and discover that they have an enhanced antiviral RNAi response, producing canonical viral small interfering RNAs upon Sindbis virus infection that are missing in human cells. Disruption of Dicer function results in increased viral load for three different RNA viruses in bat cells, indicating an interferon-independent antiviral pathway. Furthermore, our findings reveal the simultaneous engagement of Dicer and pattern-recognition receptors, such as retinoic acid-inducible gene I, with double-stranded RNA, suggesting that Dicer attenuates the interferon response initiation in bat cells. These insights advance our comprehension of the distinctive strategies bats employ to coexist with viruses.

To accurately diagnose and evaluate the degree of myocardial injury and predict myocardial infarction disease, the rapid and sensitive detection of cardiac troponin I (cTnI) is required. Therefore, a label-less electrochemical aptasensor was prepared for cTnI determination. Ionic liquid 1-hydroxyethy l-3- methyl imidazole four fluorine boric acid salt (IL)-reduced graphene oxide − four ethylene oxidation reduction five amine (rGO-TEPA)/silica (SiO2)- gold platinum (AuPt) (IL-rGO-TEPA/SiO2-AuPt) nanocomposites were synthetized as the substrate nanocomposite and were characterized using a series of characterization methods. The performance of the prepared aptasensor was characterized through electrochemical methods. Result displayed that better substrate materials were synthesized, and the prepared electrochemical aptasensor showed excellent electrochemical performance. Under optimal conditions, the electrochemical aptasensor had a salient analytical performance. The electrochemical signals linearly decreased with the logarithm of the cTnI concentration between the 0.5 pg·mL−1 and 1 × 106 pg·mL−1 concentration range (R2 value = 0.9955) and the aptasensor had a wide detection range (0.5 ∼ 1 × 106 pg·mL−1) and a low detection limit of 0.4 pg·mL−1. At the same time, the aptasensor had good selectivity, repeatability and stability. Relative standard deviation (RSD) values ranged from 3.45 % ∼ 4.97 % and the recovery rate was 97.5 % ∼ 103 % in human serum samples, the RSD values of the spiked recovery and ELISA method were less than 5 %. This study provides a new theoretical basis and method for the clinical detection of cTnI.

Objective: Metformin as a common antidiabetic drug, has recently found to exert its anti-cancer and immunomodulatory effect in numerous preclinical studies. This study aims to clarify the prognostic impact of metformin use in solid cancer patients receiving immune checkpoint inhibitors (ICIs).Methods: A retrospective cohort enrolling 516 solid cancer patients who received ICI-based therapy between 2018 and 2023 at three hospitals was analyzed. The primary endpoints included overall survival (OS) and progression-free survival (PFS). In addition, a bioinformatics analysis based on TCGA and GSE cohort was performed to investigate the prognostic significance of metformin target genes (MTGs) and their correlation with immune infiltration in non-small cell lung cancer (NSCLC) patients.Results: In the entire cohort, a total of 76 patients received metformin before and/or during ICI therapy. The global analysis demonstrated that metformin use was unrelated with the OS (p = 0.064) and PFS (p = 0.059) of ICI-treated cancer patients, which was confirmed in the subgroups of esophagus, hepatobiliary or pancreatic cancer (all p > 0.05). However, metformin use was significantly correlated with better OS (p = 0.012) and PFS (p = 0.005) in ICI-treated lung cancer patients. Metformin use was also identified as an independent favorable prognostic factor for these patients. The bioinformatics analysis identified five favorable prognostic MTGs (RPS6KA5, RORA, SH3BP5, NUPR1, and CD40LG) for NSCLC patients, all of which was downregulated in lung cancer tissues as compared with normal tissues. The expressions of five MTGs not only could effectively stratify the OS of NSCLC patients, but also was correlated with infiltration of immune cells such as CD4+ and CD8+ T cells.Conclusion: Metformin use was significantly correlated with better OS and PFS in ICI-treated lung cancer patients. MTGs has the potential to serve as novel clinical biomarkers or druggable targets for cancer immunotherapy. Considering study limitations, the actual impact of metformin use on ICI therapy needs to be clarified by more clinical trials.

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases and has become a global public health concern. Although hypertension results from a combination of factors, the specific mechanism is still unclear. However, increasing evidence suggests that gut microbiota is closely associated with the development of hypertension. We provide a summary of the composition and physiological role of gut microbiota. We then delve into the mechanism of gut microbiota and its metabolites involved in the occurrence and development of hypertension. Finally, we review various regimens for better-controlling hypertension from the diet, exercise, drugs, antibiotics, probiotics, and fecal transplantation perspectives.

Abstract Immune checkpoint blockades have been prized in circumventing and ablating the impediments posed by immunosuppressive receptors, reaching an exciting juncture to be an innovator in anticancer therapy beyond traditional therapeutics. Thus far, approved immune checkpoint blockades have principally targeted PD-1/PD-L1 and CTLA-4 with exciting success in a plethora of tumors and yet are still trapped in dilemmas of limited response rates and adverse effects. Hence, unveiling new immunotherapeutic targets has aroused immense scientific interest in the hope of expanding the clinical application of immune checkpoint blockades to scale new heights. Human leukocyte antigen-G (HLA-G), a non-classical major histocompatibility complex (MHC) class I molecule, is enriched on various malignant cells and is involved in the hindrance of immune effector cells and the facilitation of immunosuppressive cells. HLA-G stands out as a crucial next-generation immune checkpoint showing great promise for the benefit of cancer patients. Here, we provide an overview of the current understanding of the expression pattern and immunological functions of HLA-G, as well as its interaction with well-characterized immune checkpoints. Since HLA-G can be shed from the cell surface or released by various cells as free soluble HLA-G (sHLA-G) or as part of extracellular vesicles (EVs), namely HLA-G-bearing EVs (HLA-GEV), we discuss the potential of sHLA-G and HLA-GEV as predictive biomarkers. This review also addresses the advancement of HLA-G-based therapies in preclinical and clinical settings, with a focus on their clinical application in cancer.

Abstract Background Low-quality sleep and obstructive sleep apnea (OSA) can result in series of chronic diseases. Healthy diet has been considered as an effective and simple strategy to optimize sleep quality. However, current evidence on the correlation of dietary composite antioxidant intake with sleep health remained obscure. Aim of the study To determine the relationship of composite dietary antioxidant index (CDAI) and sleep health. Methods Cross-sectional analyses were based on National Health and Nutrition Examination Survey (NHANES) 2005–2008. Dietary consumption was assessed by trained staff using 24-h diet recall method and CDAI was calculated based on previous validated approach that included six antioxidants. Sleep-related outcomes were self-reported by a set of questionnaires and classified into OSA, day sleepiness, and insufficient sleep. Weighted logistic regression was conducted to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic spline (RCS) regressions were also used to evaluate the dose-response of CDAI and three sleep-related outcomes. Results A total of 7274 subjects included (mean age: 46.97 years) were enrolled in our study, including 3658 were females (52.54%) and 3616 were males (47.46%). Of them, 70.6%, 29.51%, and 35.57% of the subjects reported that they had OSA, day sleepiness and insufficient sleep, respectively. Logistic regression showed the highest quartile of CDAI was inversely associated with the risk of OSA (OR: 0.69, 95%CI: 0.49–0.97), day sleepiness (OR: 0.64, 95%CI: 0.44–0.94) and insufficient sleep (OR: 0.68, 95%CI: 0.50–0.92) compared with the lowest quartile. RCS showed linear relationship of CDAI and insufficient sleep but non-linear relationship of CDAI with OSA and day sleepiness. Conclusions Our results show that CDAI was non-linearly associated with lower risk of OSA and day sleepiness whereas a linear inverse association between CDAI and insufficient sleep was observed. These findings implicate that combined intake of antioxidants could be a promising and effective approach to optimize sleep quality for public.

Abstract Machine learning (ML) algorithms have shown potential in automatically detecting and measuring stomata. However, ML algorithms require substantial data to efficiently train and optimize models, but their potential is restricted by the limited availability and quality of stomatal images. To overcome this obstacle, we have compiled a collection of around 11,000 unique images of temperate broadleaf angiosperm tree leaf stomata from various projects conducted between 2015 and 2022. The dataset includes over 7,000 images of 17 commonly encountered hardwood species, such as oak, maple, ash, elm, and hickory, and over 3,000 images of 55 genotypes from seven Populus taxa. Inner_guard_cell_walls and whole_stomata (stomatal aperture and guard cells) were labeled and had a corresponding YOLO label file that can be converted into other annotation formats. With the use of our dataset, users can (1) employ state-of-the-art machine learning models to identify, count, and quantify leaf stomata; (2) explore the diverse range of stomatal characteristics across different types of hardwood trees; and (3) develop new indices for measuring stomata.

Abstract With the development of assisted reproductive technology, the number of twin pregnancies is increasing year by year. Given the increased risk of pregnancy complications associated with twin pregnancies, and the fact that these babies are rare and difficult to obtain through assisted reproductive technology, clinicians urgently require finding effective and safe drugs to improve pregnancy outcomes. Low-dose aspirin can not only promote placental blood supply, but also effectively anti-inflammatory. Whether Low-dose aspirin can effectively reduce the risk of pregnancy complications in this special group needs to be clarified. We therefore retrospectively analyzed 665 twin pregnancies from assisted reproduction technology, grouped according to aspirin use, and followed pregnancy outcomes to assess bleeding risk. Low-dose aspirin was found to be effective in preventing preeclampsia without a significant risk of bleeding. However, aspirin does not prevent specific complication in twin pregnancies and seems to have a better preventive effect only when the mother is under 30, which should alarm clinicians should not blindly using aspirin in this particular group.

With the leapfrog development of information and communication technology and the intensification of external competition among enterprises, after-hours work connectivity through communication devices has become a new norm in the workplace. While it offers certain conveniences, the constant connectivity it entails also imposes significant pressure on employees. How to comprehensively understand and rationally treat after-hours work connectivity has become an issue that organizations need to pay great attention to. Based on conservation of resources theory, this study analyzed 407 questionnaires to explore the “double-edged sword” effect of after-hours work connectivity on employee performance and analyzed the moderating effect of the psychological contract. The results indicate the following: (1) Proactive pathway: after-hours work connectivity promotes employees’ job crafting behaviors toward approach-oriented adjustments, thereby enhancing job performance. (2) Passive pathway: after-hours work connectivity encourages employees’ job crafting behaviors toward avoidance-oriented adjustments, leading to decreased job performance. (3) The psychological contract positively moderates the relationship between after-hours work connectivity and approach-oriented job crafting and negatively moderates the relationship between after-hours work connectivity and avoidance-oriented job crafting, regulating both the positive and negative coping pathways. The research findings contribute to assisting organizations in adopting a dialectical perspective towards and effectively utilizing after-hours work connectivity. This aids in achieving a balance between organizational effectiveness and employee well-being, seeking a mutually beneficial work paradigm, and providing managerial recommendations to promote sustainable organizational development.

Macroporous H5PMo10V2O40(n)/biochar (abbreviated as HPMoV(n)/biochar, where n is the loading amount of HPMo: 12 wt.%, 28 wt.%, 44 wt.%, 53 wt.%, and 63 wt.%) were fabricated from popcorn biocarbon and H5PMo10V2O40. The materials exhibited a pore size of 8–50 μm and high specific surface areas, allowing them to efficiently catalyze the degradation of phthalic acid esters (PAEs) in water. HPMoV(n)/biochar contained double-functional sites with strong Brønsted acidity and redox properties; additionally, biochar promoted electron transfer between the polyanions and PAEs and confined the generation of reactive oxygen species inside the pores. At the same time, macropores and high porosity endowed the materials with high adsorption capacities toward PAEs, even long carbon-chain esters such as diallyl phthalate and diethylhexyl phthalate. These characteristics allowed HPMoV(44)/biochar to degrade 80%–88% of PAEs within 90 min through tandem hydrolysis–oxidation. The mineralization of diethyl phthalate was confirmed by the 72.5% and 64.4% reductions in chemical oxygen demand and total organic carbon, respectively, at atmospheric pressure. HPMoV(44)/biochar exhibited heterogeneity and high stability in the degradation of diethyl phthalate. Furthermore, the material could be reused at least eight times with only 1.9% and 3.0% loss of mass and activity, respectively.

With the rapid advances in next-generation sequencing technology, numerous non-protein-coding transcripts have been identified, including long noncoding RNAs (lncRNAs), which are functional RNAs comprising more than 200 nucleotides. Although lncRNA-mediated regulatory processes have been extensively investigated in animals, there has been considerably less research on plant lncRNAs. Nevertheless, multiple studies on major crops showed lncRNAs are involved in crucial processes, including growth and development, reproduction, and stress responses. This review summarizes the progress in the research on lncRNA roles in several major crops, presents key strategies for exploring lncRNAs in crops, and discusses current challenges and future prospects. The insights provided in this review will enhance our comprehension of lncRNA functions in crops, with potential implications for improving crop genetics and breeding.

Silicosis is a progressive pulmonary fibrosis disease caused by long-term inhalation of silica. The early diagnosis and timely implementation of intervention measures are crucial in preventing silicosis deterioration further. However, the lack of screening and diagnostic measures for early-stage silicosis remains a significant challenge. In this study, silicosis models of varying severity were established through a single exposure to silica with different doses (2.5mg/mice or 5mg/mice) and durations (4 weeks or 12 weeks). The diagnostic performance of computed tomography (CT) quantitative analysis was assessed using lung density biomarkers and the lung density distribution histogram, with a particular focus on non-aerated lung volume. Subsequently, we developed and evaluated a stacking learning model for early diagnosis of silicosis after extracting and selecting features from CT images. The CT quantitative analysis reveals that while the lung densitometric biomarkers and lung density distribution histogram, as traditional indicators, effectively differentiate severe fibrosis models, they are unable to distinguish early-stage silicosis. Furthermore, these findings remained consistent even when employing non-aerated areas, which is a more sensitive indicator. By establishing a radiomics stacking learning model based on non-aerated areas, we can achieve remarkable diagnostic performance to distinguish early-stage silicosis, which can provide a valuable tool for clinical assistant diagnosis. This study reveals the potential of using non-aerated lung areas as a region of interest in stacking learning for early diagnosis of silicosis, providing new insights into early detection of this disease.

BackgroundSleep plays a critical role in human physiological and psychological health, and electroencephalography (EEG), an effective sleep-monitoring method, is of great importance in revealing sleep characteristics and aiding the diagnosis of sleep disorders. Sleep spindles, which are a typical phenomenon in EEG, hold importance in sleep science.MethodsThis paper proposes a novel convolutional neural network (CNN) model to classify sleep spindles. Transfer learning is employed to apply the model trained on the sleep spindles of healthy subjects to those of subjects with insomnia for classification. To analyze the effect of transfer learning, we discuss the classification results of both partially and fully transferred convolutional layers.ResultsThe classification accuracy for the healthy and insomnia subjects’ spindles were 93.68% and 92.77%, respectively. During transfer learning, when transferring all convolutional layers, the classification accuracy for the insomnia subjects’ spindles was 91.41% and transferring only the first four convolutional layers achieved a classification result of 92.80%. The experimental results demonstrate that the proposed CNN model can effectively classify sleep spindles. Furthermore, the features learned from the data of the normal subjects can be effectively applied to the data for subjects with insomnia, yielding desirable outcomes.DiscussionThese outcomes underscore the efficacy of both the collected dataset and the proposed CNN model. The proposed model exhibits potential as a rapid and effective means to diagnose and treat sleep disorders, thereby improving the speed and quality of patient care.

This study addresses the low water productivity (WP) of traditional flood irrigation (FI) and the mismatch between the wet zone of surface drip irrigation (SDI) and the root activity layer of fragrant pear. A fixed field experiment was conducted in Xinjiang, northwest China in 2021 − 2023. The experiment was designed as a two-factor, completely randomized trial with three lateral depths of Subsurface drip irrigation (SSDI) gradients set at 20 cm (D1), 30 cm (D2) and 40 cm (D3) and three irrigation gradients: W1 (3750 m³ ha−1); W2 (5250 m³ ha−1); and W3 (6750 m³ ha−1), using SDI (6750 m³ ha−1) and FI (9750 m³ ha−1) as the controls. The effects of these factors on soil moisture, crop water consumption (ETc), fruit quality, yield, WP and net profit were analyzed. The results revealed that the average soil moisture content increased with the lateral depth and irrigation amount. Principal component analysis determined D2W3 to be the treatments with the best overall quality in 2021–2023. On average, compared with SDI and FI, SSDI increased yield by 13.14% and 17.03%, and WP by 44.65% and 137.23%, respectively. A comprehensive Moisture-Yield-Quality-Efficiency evaluation model was established using the Projection Pursuit Classification model based on the Real Coded Accelerating Genetic Algorithm (RAGA-PPC). The comprehensive evaluation was optimized at the lateral depth of 30 cm and an irrigation amount of 6750 m³ ha−1. This study is a crucial reference for further research on perennial fruit trees to improve fruit quality and WP.

ObjectiveAccumulated evidence has suggested a relatively high recurrence rate in early-stage cervical cancer (CC) patients with risk factors. This study aimed to assess the efficacy and safety of consolidation chemotherapy following adjuvant therapy (concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone) in stage IB-IIA CC patients with risk factors.MethodsA total of 237 stage IB-IIA CC patients who received radical surgery between January 2014 and December 2021 were included in the retrospective study. According to the types of adjuvant therapies, the patients were classified into the control group (CCRT or RT alone) and the study group (consolidation chemotherapy following CCRT or RT alone). The propensity score matching (PSM) was used to balance baseline characteristics between the two groups. The primary end points of the study were disease-free survival (DFS) and overall survival (OS).ResultsFor the entire cohort, no significant difference was observed in the DFS or OS between the study and control group, which was also confirmed in the PSM cohort (n=124). The multivariate analysis identified the high-risk factor type was an independent adverse prognostic factor for the patients. In patients with high risk factors, consolidation chemotherapy following adjuvant therapy was significantly associated with better clinical outcomes and identified as an independent prognostic favorable factor. Moreover, this association remained statistically significant in high-risk patients with ≥2 metastatic lymph nodes. In patients with intermediate risk factors, consolidation chemotherapy following adjuvant therapy was unrelated to DFS or OS. The safe assessment demonstrated consolidation chemotherapy following adjuvant therapy was significantly correlated with higher rates of ≥ grade 3 hematologic toxicities in both the global and subgroup analysis stratified by risk factor type.ConclusionConsolidation chemotherapy after adjuvant therapy provided survival benefits in stage IB-IIA CC patients with high risk factors, particularly those with ≥2 metastatic lymph nodes. However, related hematologic toxicities should be alerted in patient management. The actual efficacy and safety of consolidation chemotherapy still need to be investigated in more well-designed clinical trials.

Abstract Background Frailty is common and not limited to older age group. Serum α-Klotho works as a biomarker of anti-aging effect. However, there is limited research about the relationship between them in middle-aged and older people and controversy still exists. Methods Based on data from National Health and Nutrition Examination Survey (NHANES) 2007–2016, we constructed weighted logistic regression models and conducted sensitivity tests to investigate the correlation between frailty and α-Klotho among people aged 40 to 79. And then their relationship was visualized by Restricted Cubic Spline (RCS). Finally, the stratified analyses and interaction tests of covariables was presented in the forest plot. Results A total of 7052 individuals were involved in this study, with mean age of 62.76 ± 0.18 years and females accounting for 51.05%. 2554 of them were in “frailty”. After adjustment for relevant covariables, weighted logistic regression models showed that the odds ratio and 95% confidence interval [ORs (95%CI)] of correlation between frailty and Natural Logarithm(ln)-transformed α- Klotho[ln(α-Klotho)] was 0.63 (0.50, 0.79); we then performed a sensitivity analysis and found that the results remained stable. In model 3, individuals in quartiles 2, 3, and 4 showed statistical differences compared with the lowest ln(α-Klotho) quartiles, ORs (95% CI) were 0.74 (0.59, 0.93), 0.72 (0.57, 0.91), 0.71 (0.57, 0.87), respectively. Subsequently, non-linear associations were exhibited by RCS (p

Abstract Basal cell carcinoma (BCC) is the most common cancer with a rising incidence among white-skinned individuals. A number of epidemiological studies have suggested that obesity and serum 25-hydroxy-vitamin D (25(OH)D) levels may affect the arising of BCC. To address this, we selected 443 and 96 single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) and serum level of 25(OH)D from large-scale genome-wide association studies (GWAS), respectively. The univariable and multivariable two-sample Mendelian randomization (MR) analyses were conducted with a series of sensitivity analyses to ensure the results were reliable and reproducible. The results of univariable two-sample MR analysis showed that higher BMI was related to lower risk for BCC (Odds ratio(OR) = 0.90; 95% confidence interval (CI),[0.81,0.99]; p = 0.02). In addition, this causal effect of BMI on BCC still remained (OR = 0.88; 95%CI,[− 0.22, − 0.03], p-value = 0.008) after adjusting for 25(OH)D level in the multivariable MR analysis. However, the results suggested that 25(OH)D level was not associated with BCC(OR = 1.02; 95%CI, [0.94,1.09], p-value = 0.67). In conclusion, similar to the conclusions of retrospective observational studies, the MR results indicate that high BMI is an independent protective factor for BCC. Meanwhile, vitamin D levels may not be causally associated with the risk of basal cell carcinoma and increasing vitamin D supplementation is unlikely to reduce the risk.

ABSTRACT: Milk-clotting enzyme (MCE) is the essential active agents in dairy processing. The traditional MCE is mainly obtained from animal sources, in which calf rennet is the most widely used in cheese industry. Traditional MCE substitute is becoming necessary due to its limited production and increased cheese consumption. A novel traditional MCE substitute was produced from Bacillus velezensis DB219 in this study. The DB219 MCE exhibited a notable specific activity of 6,110 Soxhlet units/mg and 3.16-fold purification yield with 28.87% recovery through ammonium sulfate fractionation and DEAE-Sepharose Fast Flow. The purified DB219 MCE was a metalloprotease with a molecular weight of 36 kDa. The DB219 MCE was weak acid resistance and stable at pH 6.0 to 10.0 and temperature

In the current era of energy conservation and emission reduction, the development of electric and other new energy vehicles is booming. With their various attributes, lithium batteries have become the ideal power source for new energy vehicles. However, lithium-ion batteries are highly sensitive to temperature changes. Excessive temperatures, either high or low, can lead to abnormal operation of the batteries, posing a threat to the safety of the entire vehicle. Therefore, developing a reliable and efficient Battery Thermal Management System (BTMS) that can monitor battery status and prevent thermal runaway is becoming increasingly important. In recent years, deep learning has gradually become widely applied in various fields as an efficient method, and it has also been applied to some extent in the development of BTMS. In this work, we discuss the basic principles of deep learning and related optimization principles and elaborate on the algorithmic principles, frameworks, and applications of various advanced deep learning methods in BTMS. We also discuss several emerging deep learning algorithms proposed in recent years, their principles, and their feasibility in BTMS applications. Finally, we discuss the obstacles faced by various deep learning algorithms in the development of BTMS and potential directions for development, proposing some ideas for progress. This paper aims to analyze the advanced deep learning technologies commonly used in BTMS and some emerging deep learning technologies and provide new insights into the current combination of deep learning technology in new energy trams to assist the development of BTMS.

Increasing oil production is crucial for multilayer co-production. When there are significant differences in the permeability of each layer, an interlayer contradiction arises that can impact the recovery efficiency. After a number of tests and the establishment of a mathematical model, the effects of permeability contrast on oil production for water flooding were revealed. In the meantime, the developed mathematical model was solved using the Buckley–Lever seepage equation. Ultimately, the accuracy of the established model was confirmed by comparing the simulated outcomes of the mathematical model with the experimental results. The findings indicate that when permeability contrast increases, the production ratio of the high-permeability layer will improve. This is primarily due to the low-permeability layer’s production contribution rate decreasing. The accuracy of the established model is ensured by an error of less than 5% between the results of the experiment and the simulation. When the permeability contrast is less than three, the low-permeability layer can be effectively used for three-layer commingled production. However, when the permeability contrast exceeds six, the production coefficient of the low-permeability layer will be less than 5%, which has a significant impact on the layer’s development.

The 360 degree feedback evaluation method is a multidimensional, comprehensive assessment method. Evaluators may hesitate among multiple evaluation values and be simultaneously constrained by the biases and cognitive errors of the evaluators, evaluation results are prone to unfairness and conflicts. To overcome these issues, this paper proposes a consensus-based 360 degree feedback evaluation method with linguistic distribution assessments. Firstly, evaluators provide evaluation information in the form of linguistic distribution. Secondly, utilizing an enhanced ordered weighted averaging (OWA) operator, the model aggregates multi-source evaluation information to handle biased evaluation information effectively. Subsequently, a consensus-reaching process is established to coordinate conflicting viewpoints among the evaluators, and a feedback adjustment mechanism is designed to guide evaluators in refining their evaluation information, facilitating the attainment of a unanimous evaluation outcome. Finally, the improved 360 degree feedback evaluation method was applied to the performance evaluation of the project leaders in company J, thereby validating the effectiveness and rationality of the method.

Abstract Endochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of α-parvin, an integrin-associated focal adhesion protein, from murine limbs causes defects in endochondral ossification and dwarfism. The mutant long bones were shorter but wider, and the growth plates became disorganized, especially in the proliferative zone. With two-photon time-lapse imaging of bone explant culture, we provide direct evidence showing that α-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of α-parvin increased binucleation, elevated cell death, and caused dilation of the resting zones of mature growth plates. Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones (i.e., resting, proliferative, and hypertrophic zones) of the growth plates. Our results demonstrate a crucial role of α-parvin in long bone development and shed light on the cellular mechanism through which α-parvin regulates the longitudinal growth of long bones.

Abstract Purpose To investigate the effectiveness of an automatic analysis framework based on 3D-CT multi-scale features in predicting Ki67 expression levels in substantial renal cell carcinoma (RCC). Methods This retrospective study was conducted using multi-center cohorts consisting of 588 participants with pathologically confirmed RCC. The participants were divided into an internal training set (n = 485) and an external testing set (n = 103) from four and one local hospitals, respectively. The proposed automatic analytic framework comprised a 3D kidney and tumor segmentation model constructed by 3D UNet, a 3D-CT multi-scale features extractor based on the renal–tumor feature, and a low or high Ki67 prediction classifier using XGBoost. The framework was validated using a fivefold cross-validation strategy. The Shapley additive explanation (SHAP) method was used to determine the contribution of each feature. Results In the prediction of low or high Ki67, the combination of renal and tumor features achieved better performance than any single features. Internal validation using a fivefold cross-validation strategy yielded AUROC values of 0.75 ± 0.1, 0.75 ± 0.1, 0.83 ± 0.1, 0.77 ± 0.1, and 0.87 ± 0.1, respectively. The optimal model achieved an AUROC of 0.87 ± 0.1 and 0.82 ± 0.1 for low vs. high Ki67 prediction in the internal validation and external testing sets, respectively. Notably, the tumor first-order-10P was identified as the most influential feature in the model decision. Conclusions Our study suggests that the proposed automatic analysis framework based on 3D-CT multi-scale features has great potential for accurately predicting Ki67 expression levels in substantial RCC. Critical relevance statement Automatic analysis framework based on 3D-CT multi-scale features provides reliable predictions for Ki67 expression levels in substantial RCC, indicating the potential usage of clinical applications. Graphical abstract

Abstract The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-β (TGF-β) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-β inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs.

ObjectiveIncreasing studies have highlighted the potential utility of non-invasive prognostic biomarkers in advanced lung cancer patients receiving immune checkpoint inhibitor (ICI) based anti-cancer therapies. Here, a novel prognostic predictor named as C-PLAN integrating C-reactive protein (CRP), Performance status (PS), Lactate dehydrogenase (LDH), Albumin (ALB), and derived Neutrophil-to-lymphocyte ratio (dNLR) was identified and validated in a single-center retrospective cohort.MethodsThe clinical data of 192 ICI-treated lung cancer patients was retrospectively analyzed. The pretreatment levels of CRP, PS, LDH, ALB and dNLR were scored respectively and then their scores were added up to form C-PLAN index. The correlation of C-PLAN index with the progression-free survival (PFS) or overall survival (OS) was analyzed by a Kaplan–Meier model. The multivariate analysis was used to identify whether C-PLAN index was an independent prognostic predictor.ResultsA total of 88 and 104 patients were included in the low and high C-PLAN index group respectively. High C-PLAN index was significantly correlated with worse PFS and OS in ICI-treated lung cancer patients (both p

Summary: In animal cells, the dysregulation of centrosome duplication and cohesion maintenance leads to abnormal spindle assembly and chromosomal instability, contributing to developmental disorders and tumorigenesis. However, the molecular mechanisms involved in maintaining accurate centrosome number control and tethering are not fully understood. Here, we identified coiled-coil domain-containing 102A (CCDC102A) as a centrosomal protein exhibiting a barrel-like structure in the proximal regions of parent centrioles, where it prevents centrosome overduplication by restricting interactions between Cep192 and Cep152 on centrosomes, thereby ensuring bipolar spindle formation. Additionally, CCDC102A regulates the centrosome linker by recruiting and binding C-Nap1; it is removed from the centrosome after Nek2A-mediated phosphorylation at the onset of mitosis. Overall, our results indicate that CCDC102A participates in controlling centrosome number and maintaining centrosome cohesion, suggesting that a well-tuned system regulates centrosome structure and function throughout the cell cycle.

Background Strain analysis is a sensitive method for the assessment of ventricular structural or functional alterations. The authors aimed to determine whether right ventricular (RV) strain parameters can discriminate patients with revised Task Force Criteria–diagnosed arrhythmogenic RV cardiomyopathy (ARVC) incremental to the existing cardiovascular magnetic resonance (CMR) criteria, thus improving the diagnostic yield of CMR in ARVC. Methods and Results A total of 74 patients with revised Task Force Criteria–diagnosed ARVC (37 borderline and 37 definite) and 37 controls were retrospectively enrolled for analysis. Using CMR feature tracking, RV global longitudinal (GLS), circumferential, and radial strain of all participants were evaluated. Compared with controls, the study patients demonstrated significantly impaired global biventricular strain in all 3 directions (all P50% presenting with impaired RV GLS. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated an overall diagnostic accuracy of 90%. The likelihood ratio test showed a significant incremental diagnostic value of RV GLS (P=0.02) over the existing CMR major criteria. Conclusions The current study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for patients with borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.

In the process of urbanization, the low effectiveness of urban water governance has been driven by multiple causes. Among them, a perplexing and misunderstood issue has been that stabilization or even enhancement of urban water areas may often conceal detrimental changes in the ecological function of the urban hydrological system. To address this phenomenon, a typical plains river network city is taken as the research object against the background of China's urban development. Specifically, we studied the spatial evolution of the river system in the city of Luohe, China, over the past 30 years. We attempt to measure the impact of urbanization on the Luohe river system through remote sensing techniques across four dimensions: water area, number and class of rivers, and river grid density. The results show that, (1) from 1988 to 2022, the water area fluctuated and even increased slightly, with a rate of change of + 1.46 %. During this period the area of forest decreased, while the area of urbanized land increased. Given the stable area of the hydrological system it is easy to assume the river has not deteriorated in ecological structure and function. However, our further results show that (2) the length and number of rivers have decreased. (3) The river unit density decline rates were 13.89 %, 12.90 %, 11.11 %, 4.17 %, and 8.70 %, respectively, from 1988 to 2022. This indicates a regional simplification of the structure of the network of river systems in the area. (4) Morans’ I for the river unit density over six periods showed a positively correlated, indicating that the degree of concentration of river density decreased year by year, and the significant clustering distance of density grids increased, and the high-density centroid of gravity of the river network consistently shifted from north to southwest over the analysis period. In summary, our analyses showed that the structure of the Luohe river system has changed to few, wide and concentrated channels. Natural river geomorphology has been transformed to channelized and hardened channels, then to concentration into single main channels, with tributaries combined and concentrated into few main linear channels, explaining why smaller rivers system units have been eliminated and lost through attrition.

Objective: To investigate the therapeutic potential of dimethyl fumarate (DMF) in improving erectile function of bilateral cavernous nerve injury (BCNI) rats, along with elucidating its underlying mechanisms. Methods: A BCNI rat model was established by clamping bilateral cavernous nerve (CN). DMF was given by gavage at low (20 mg/kg/day) and high (40 mg/kg/day) dosages for a duration of 4 weeks. Erectile function was assessed by electrical stimulation of CN. Penis and CN tissues were collected for subsequent analysis. Additionally, PC-12 cell line was used to verify the mechanism of DMF in vitro. Nfe2l2 or Ho-1 gene knockdown PC-12 cell lines were constructed by lentiviral transfection, respectively. A damaged cell model was induced using H2O2. And then molecular biological methods were employed to analyze cellular molecules and proteins. Results: DMF administration for 4 weeks led to improvements in erectile function, reduced fibrosis of penis corpus cavernosum in BCNI rats. The morphology of CN was improved and the number of nerve fibers increased. Furthermore, the levels of nNOS, NO, and cGMP were increased, while Ca2+ was decreased in penis corpus cavernosum. Notably, the levels of ROS, 3-NT and NLRP3 inflammasomes production were reduced, alongside increased expression of Nrf2 and HO-1 proteins in the dorsal penile nerve (DPN) and CN. In vitro, DMF increased cell viability, reduced ROS level, promoted SOD, diminished 3-NT, MDA and DNA damage markers, and inhibited the activation of NLRP3 inflammasomes in H2O2 induced PC-12 cells. Nfe2l2 knockdown and Ho-1 knockdown significantly attenuated the protective effect of DMF, respectively. Furthermore, inhibition of ROS production by N-acetylcysteine led to a reduction in NLRP3 inflammasome activation in H2O2 induced PC-12 cells. Conclusions: DMF improved erectile function of BCNI rats by protecting nerves through inhibiting oxidative stress and the activation of NLRP3 inflammasome-mediated pyroptosis via activation of Nrf2/HO-1 pathway.

AbstractBackground Diabetic kidney disease (DKD) is one of the most common chronic complications of type 2 diabetes mellitus (T2DM), and it is particularly important to identify a high-quality method for evaluating disease progression. Urinary exosomes contain microRNA that might promise early diagnostic and monitoring markers of DKD. The present study aimed to identify novel exosome-related markers associated with inflammation and fibrosis to assess the progression of DKD.Method Exosomes were extracted from the urine of 83 participants to determine the expression levels of miRNA-615-3p and miRNA-3147 in 20 healthy people, 21 patients with T2DM and 42 patients with DKD, as determined by RT-qPCR. The circulating expression level of TGF-β1 was detected by ELISA. Serum Cystatin C was measured by a latex-enhanced immunoturbidimetric method. The correlation analyses were performed for all clinical and laboratory parameters.Result The expression level of urinary exosomal miRNA-615-3p in DKD patients was significantly higher than that in the control group and the T2DM group by RT-qPCR. The expression of miRNA-3147 showed an upward trend in the three groups of subjects, but it was not statistically significant. The urinary exosomal miRNA-615-3p was positively correlated with serum Cystatin C, plasma TGF-β1, creatinine, BUN, PCR and 24-h urine protein, and negatively correlated with eGFR and albumin. The diagnostic efficacy of urinary exosomal miRNA-615-3p combined with the ACR was higher than that of ACR alone.Conclusions Urinary exosomal miRNA-615-3p may be used as a novel biomarker for evaluating the progression of DKD, and may be involved in the process of inflammation and fibrosis in DKD. The combined diagnosis of urinary exosomal miRNA-615-3p and ACR may be used as more stable and sensitive diagnostic criteria for DKD.