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Abstract Microvascular obstruction (MVO) is linked with adverse clinical outcome in acute coronary syndrome (ACS) patients, therefore, early prediction of MVO with non-invasive peripheral microcirculation is crucial in facilitating optimal treatment. Current study aims to analyze the significance of opisthenar microvessel area (OMA, measured using optical coherence tomography, OCT) in predicting coronary stenosis (Gensini score, GS) and short-term cardiac recovery of ACS patients and the results were compared to those of arterial stiffness parameters (Pulse Wave Velocity, PWV; Ankle-Brachial Index; ABI). Results showed that cardiac functional parameters (e.g. ejection fraction, EF; fractional shortening, FS) and OMA were higher in normal/low risk (GS 0–≤ 20, n = 69) compared to medium/high risk patients (GS > 20, n = 44, P

Abstract Background Crohn’s disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall. Case presentation In this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment. Conclusion In clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection.

Abstract Background Loneliness in older adults, exacerbated by widowhood, is a significant public health concern. While widowhood can lead to changes in living arrangements, its impact on loneliness may vary across cultural contexts. In Western societies, widowhood often results in older adults living alone, which can intensify feelings of loneliness. However, in China, the cultural norm of filial piety and multigenerational households may lead to different outcomes. As few studies have explored this connection over time, this research seeks to bridge this gap using data from older Chinese adults. Methods Using 16 years of data from the Chinese Longitudinal Healthy Longevity Survey, which covers 21,986 individuals aged 65–104 years, we conducted causal mediation analysis to test if changes in living arrangements (i.e., living alone versus with children) serve as a mediator between widowhood and loneliness. The potential variation in this mediation effect by gender and age was also evaluated. Results Spousal loss was associated with an increase in loneliness. However, living with adult children post-loss reduced this emotional strain compared to living alone. The mediating influence of living arrangements was notably stronger for women than men and intensified with age in long term. In the short term, the mediating impact of living arrangements is significantly greater, particularly for older adults under 80 years old. Conclusion Alterations in living arrangements play a pivotal role in mediating the effects of widowhood on loneliness among China’s older adults. Encouraging co-residence with adult children post-spousal loss, especially for older women and the eldest age groups, might mitigate social isolation. These insights both deepen our theoretical understanding and suggest interventions to enhance the well-being of widowed older adults.

Abstract Background Middle-aged and elderly individuals are the most susceptible groups for metabolic diseases, with their dietary behaviors being significant influencing factors. Exploring the association between overall dietary behaviors and obesity metabolic phenotypes is crucial for early prevention and control of chronic diseases, precision treatment and personalized interventions. Methods We conducted a cross-sectional study of 15,160 middle-aged and older adults between June 2019 and August 2021 to collect information on their body mass index (BMI), biochemical indices and disease history. The population was classified into four categories by the criteria of obesity metabolic phenotypes: metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO). Scores were calculated based on compliance with healthy eating behavior patterns (appropriate or light dietary taste, moderately soft and hard food, slightly hot food temperature, medium or slow eating speed, daily intake of dietary supplements and eating with others), and the population was categorized into subgroups 0–2 (did not meet and met only 1 or 2), 3–4 (met 3 or 4), 5–6 (met 5 or 6). The relationship between dietary behavior patterns and different obesity metabolic phenotypes in middle-aged and elderly people were analyzed by multi-categorical logistic regression model. Results Compared with the 5–6 subgroup, the dietary behavior patterns of 0–2 and 3–4 scores were risk factors for MUNO, MHO and MUO (P

BackgroundBone health is important for older adults, and vitamin K (VK) is central to regulating bone formation and promoting bone health. However, whether VK can reduce the risk of osteoporosis and bone loss is unclear. This study hypothesized that different levels of VK intake exert varying effects on bone health in people aged over 50 years.MethodsIndividuals aged above 50 years were recruited from the National Health and Nutrition Examination Survey. VK intake, based on 24-h dietary recall, was divided into three groups, namely the high, medium, and low groups, by sex and tertile. Weighted multiple logistic regression was used to investigate the effects of VK intake on the risk of osteoporosis and bone loss at the femoral neck, trochanter, intertrochanter, total femur, lumbar spine, and overall.ResultsThis study included 5,075 individuals. Of them, 1,001 (18%) had osteoporosis (808 women, 83%) and 2,226 (46%) had osteopenia (1,076 women, 54%). Overall, a medium level of VK intake was associated with a reduced risk of bone loss. In women, medium- [odds ratio, OR (95% confidence interval, CI): 0.66(0.47, 0.93)] and high-level [OR (95% CI): 0.71(0.52, 0.98)] VK intake were associated with a decreased risk of osteoporosis. In contrast, only medium-level VK intake was associated with a reduced risk of bone loss [OR (95% CI): 0.58(0.41, 0.81)]. Similar results were obtained for the trochanter, intertrochanter, total femur, and lumbar spine. In men, only medium-level VK intake was associated with a reduced risk of bone loss at the femoral neck [OR (95% CI): 0.66(0.48, 0.90)], whereas high-level VK intake corresponded to a reduced risk of bone loss to the lumbar spine [OR (95% CI): 0.68(0.47, 0.99)]. Nonetheless, VK intake levels did not affect the risk of osteoporosis.ConclusionThis study demonstrates sex- and bone-site-specific variations in the associations between VK intake levels and bone health in individuals aged over 50 years. Further large-scale cohort studies or randomized controlled trials are warranted to explore the effects of different VK intake levels on bone health in people regardless of their sex and bone site.

Abstract Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre‐pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE‐induced non‐alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15–60 mg kg−1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR‐142‐3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR‐142‐3p mitigated these manifestations. The origin of reduced miR‐142‐3p levels is traced to hypermethylation in the miR‐142‐3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR‐142‐3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR‐142‐3p as a potential therapeutic target for NASH induced by paternal environmental adversities.

BackgroundStudies have shown that patients have difficulty understanding medical jargon in electronic health record (EHR) notes, particularly patients with low health literacy. In creating the NoteAid dictionary of medical jargon for patients, a panel of medical experts selected terms they perceived as needing definitions for patients. ObjectiveThis study aims to determine whether experts and laypeople agree on what constitutes medical jargon. MethodsUsing an observational study design, we compared the ability of medical experts and laypeople to identify medical jargon in EHR notes. The laypeople were recruited from Amazon Mechanical Turk. Participants were shown 20 sentences from EHR notes, which contained 325 potential jargon terms as identified by the medical experts. We collected demographic information about the laypeople’s age, sex, race or ethnicity, education, native language, and health literacy. Health literacy was measured with the Single Item Literacy Screener. Our evaluation metrics were the proportion of terms rated as jargon, sensitivity, specificity, Fleiss κ for agreement among medical experts and among laypeople, and the Kendall rank correlation statistic between the medical experts and laypeople. We performed subgroup analyses by layperson characteristics. We fit a beta regression model with a logit link to examine the association between layperson characteristics and whether a term was classified as jargon. ResultsThe average proportion of terms identified as jargon by the medical experts was 59% (1150/1950, 95% CI 56.1%-61.8%), and the average proportion of terms identified as jargon by the laypeople overall was 25.6% (22,480/87,750, 95% CI 25%-26.2%). There was good agreement among medical experts (Fleiss κ=0.781, 95% CI 0.753-0.809) and fair agreement among laypeople (Fleiss κ=0.590, 95% CI 0.589-0.591). The beta regression model had a pseudo-R2 of 0.071, indicating that demographic characteristics explained very little of the variability in the proportion of terms identified as jargon by laypeople. Using laypeople’s identification of jargon as the gold standard, the medical experts had high sensitivity (91.7%, 95% CI 90.1%-93.3%) and specificity (88.2%, 95% CI 86%-90.5%) in identifying jargon terms. ConclusionsTo ensure coverage of possible jargon terms, the medical experts were loose in selecting terms for inclusion. Fair agreement among laypersons shows that this is needed, as there is a variety of opinions among laypersons about what is considered jargon. We showed that medical experts could accurately identify jargon terms for annotation that would be useful for laypeople.

Abstract The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.

Abstract Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, Gi/o, and MCHR2 can only couple to Gq/11. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with Gi and MCH-activated MCHR2 with Gq at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

Abstract Objective This study focused on analyzing the clinical value and effect of magnetic resonance imaging plus computed tomography (MRCT) and CT in the clinical diagnosis of cerebral palsy in children. Methods From February 2021 to April 2023, 94 children diagnosed with cerebral palsy were selected from our hospital for study subjects. These patients were divided into CT and MRI groups, with CT examination given to the CT group and MRI examination given to the MRI group. The positive rate of the two examination methods in the diagnosis of cerebral palsy was compared, different imaging signs in two groups of children with cerebral palsy were compared, and the diagnostic test typing results between two groups were further analyzed. Results The diagnostic positivity rate of the children in the MRI group was 91.49%, which was significantly higher than that of the children in the CT group (70.21%) (P 0.05). Differences between the two groups examined for cerebral palsy subtypes were not significant (P > 0.05). Conclusion The positive rate of pediatric cerebral palsy examined by MRI is higher than that of CT diagnosis, but the clinic should organically combine the two to further improve the detection validity and accuracy.

During pregnancy, the maternal body undergoes a series of adaptative physiological changes, leading to a slight increase in serum bile acid (BA) levels. Although the fetal liver can synthesize BAs since the first trimester through the alternative pathway, the BA metabolic system is immature in the fetus. Compared to adults, the fetus has a distinct composition of BA pool and limited expression of BA synthesis enzymes and transporters. Besides, the “enterohepatic circulation” of BAs is absent in fetus. Thus, fetal BAs need to be transported to the mother through the placenta for further metabolism and excretion, and maternal BAs can also be transported to the fetus. That is what we call the “fetal-placental-maternal BA circulation”. Various BA transporters and nuclear receptors are essential for maintaining the balance of this BA circulation to ensure normal fetal development. However, prenatal adverse environments can alter fetal BA metabolism, resulting in intrauterine developmental abnormalities and susceptibility to a variety of adult chronic diseases. This review summarizes the current understanding of the fetal-placental-maternal BA circulation and discusses the effects of prenatal adverse environments on this particular BA circulation, aiming to provide a theoretical basis for exploring early prevention and treatment strategies for BA metabolism-associated adverse pregnancy outcomes and long-term impairments.

Many autologous melanocytes are required for surgical treatment of depigmentation diseases such as vitiligo. However, primary cultured melanocytes have a limited number of in vitro passages. The production of functional epidermal melanocytes from stem cells provides an unprecedented source of cell therapy for vitiligo. This study explores the clinical application of melanocytes induced by hair follicle neural crest stem cells (HFNCSCs). This study established an in vitro differentiation model of HFNCSCs into melanocytes. Results demonstrate that most differentiated melanocytes expressed the proteins C-KIT, MITF, S–100B, TYRP1, TYRP2, and tyrosinase. The HFNCSC-derived melanocytes were successfully transplanted onto the dorsal skin of mice and survived in the local tissues, expressing marker protein of melanocytes. In conclusion, HFNCSCs in mice can be induced to differentiate into melanocytes under specific conditions. These induced melanocytes exhibit the potential to facilitate repigmentation in the lesion areas of vitiligo-affected mice, suggesting a promising avenue for therapeutic intervention.

Plant spotted leaf (spl) mutants are useful to reveal the regulatory mechanisms of immune responses. Thus, in crop plants, their agronomic traits, especially the grain quality are usually ignored. Here, we characterized a rice spl mutant named spl-A (spotted leaf mutant from A814) that shows autoimmunity, broad-spectrum disease resistance and growth deterioration including decreased rice quality. A single nucleotide mutation of C1144T, which leads to change of the 382nd proline to serine, in the gene encoding the ATPases associated with diverse cellular activities (AAA)-type ATPase LRD6-6 is responsible for the phenotype of the spl-A mutant. Mechanistically, this mutation impairs LRD6-6 ATPase activity and disrupts its interaction with endosomal sorting complex required for transport (ESCRT)-III subunits OsSNF7.1/7.2/7.3. And thus, leading to compromise of multivesicular bodies (MVBs)-mediated vesicle trafficking and accumulation of ubiquitinated proteins in both leaves and seeds of spl-A. Therefore, the immune response of spl-A is activated, and the growth and grain quality are deteriorated. Our study identifies a new amino acid residue that important for LRD6-6 and provides new insight into our understanding of how MVBs-mediated vesicle trafficking regulates plant immunity and growth, including grain quality in rice.

Feeding the increasing global population and reducing the carbon footprint of agricultural activities are two critical challenges of our century. Growing crops under protected horticulture and precise crop monitoring have emerged to address these challenges. Crop monitoring in commercial protected facilities remains mostly manual and labour intensive. Using computer vision to solve specific problems in image-based crop monitoring in these compact and complex growth environments is currently hindered by the scarcity of available data. We collected an RGBD dataset for vertically supported, hydroponically-grown capsicum plants in a commercial-scale glasshouse facility to fill this gap. Data were collected weekly using a single top-angled stereo camera mounted on a mobile platform running between the hydroponic gutters. The RGBD streams covered 80 % of the crop growing season in three different light conditions. The metadata include camera configurations and light condition information. Manually measured plant heights of ten selected plants per gutter are provided as ground truth. The images covered the whole plants and focused on the top third. This dataset will support research on plant height estimation, plant organ identification, object segmentation, organ measurements, 3D reconstruction, 3D data processing, and depth noise reduction. The usability of the dataset has been successfully demonstrated in a previously published study on plant height estimation using machine learning and 3D point cloud.

Abstract Background The pathogenesis of vitiligo remains unclear. The genes encoding vitiligo-related RNA-binding proteins (RBPs) and their underlying pathogenic mechanism have not been determined. Results Single-cell transcriptome sequencing (scRNA-seq) data from the CNCB database was obtained to identify distinct cell types and subpopulations and the relative proportion changes in vitiligo and healthy samples. We identified 14 different cell types and 28 cell subpopulations. The proportion of each cell subpopulation significantly differed between the patients with vitiligo and healthy groups. Using RBP genes for unsupervised clustering, we obtained the specific RBP genes of different cell types in vitiligo and healthy groups. The RBP gene expression was highly heterogeneous; there were significant differences in some cell types, such as keratinocytes, Langerhans, and melanocytes, while there were no significant differences in other cells, such as T cells and fibroblasts, in the two groups. The melanocyte-specific RBP genes were enriched in the apoptosis and immune-related pathways in the patients with vitiligo. Combined with the bulk RNA-seq data of melanocytes, key RBP genes related to melanocytes were identified, including eight upregulated RBP genes (CDKN2A, HLA-A, RPL12, RPL29, RPL31, RPS19, RPS21, and RPS28) and one downregulated RBP gene (SLC3A2). Cell experiments were conducted to explore the role of the key RBP gene SLC3A2 in vitiligo. Cell experiments confirmed that melanocyte proliferation decreased, whereas apoptosis increased, after SLC3A2 knockdown. SLC3A2 knockdown in melanocytes also decreased the SOD activity and melanin content; increased the Fe2+, ROS, and MDA content; significantly increased the expression levels of TYR and COX2; and decreased the expression levels of glutathione and GPX4. Conclusion We identified the RBP genes of different cell subsets in patients with vitiligo and confirmed that downregulating SLC3A2 can promote ferroptosis in melanocytes. These findings provide new insights into the pathogenesis of vitiligo.

Abstract Background The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. Methods Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. Results THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (

Abstract Background The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. Methods In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. Results The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. Conclusion The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Deep well rescue technology refers to the key technologies involved in various aspects of rescuing trapped personnel during the process of deep well accident rescue. It mainly includes environmental detection technology, life detection technology, deep well rapid demolition technology, emergency communication network construction technology, and other auxiliary technologies to ensure the smooth progress of deep well accident rescue. Deep well rescue equipment refers to necessary hardware equipment and software platforms during the implementation of deep well rescue technology. Studying deep well rescue technology and equipment is crucial for ensuring the safety of trapped personnel and reducing accident losses. The current research status of deep well rescue equipment and key technologies is analyzed. It is pointed out that existing rescue technologies and equipment cannot fully meet the complex and changing environmental requirements. There are problems such as insufficient research on the universality and specificity of rescue equipment, the need to improve the intelligence level of rescue equipment, difficulty in meeting the needs of complex rescue environments with network collaboration capabilities, and insufficient innovation research on rescue equipment. In order to solve the above issues, the development trend of deep well rescue equipment and technology is discussed. ① Deep well rescue equipment should be divided into specialized and universal categories based on different rescue scenarios. A single equipment should develop towards multifunctionality, high reliability, and high mobility. ② Rescue equipment is intelligent, precise, and self decision-making, achieving a rescue mode of intelligent equipment as the main focus and personnel as the auxiliary. ③ It is suggested to build a rapid networking, multi-mode networking, and integrated rescue network platform. ④ Although TDLAS integration does not currently meet rescue standards, its high resolution, high sensitivity, and integrability will play an important role in the future, achieving high integration, lightweight, and efficiency of environmental monitoring equipment.

Abstract Background This study aims to explore the effect of nutritional impact symptoms (NIS) on oral nutritional supplements (ONS) energy intake and use days among head and neck cancer (HNC) patients. Methods A cross‐sectional study was conducted among HNC patients in a hospital in western China between January 2019 and June 2020. The NIS was from the Patient‐Generated Subjective Global Assessment (PG‐SGA) scale. Mann–Whitney test was used to examine the differences between different kinds of NIS and ONS use days. Binary logistic regression was used to determine the effect of NIS on ONS energy intake. Results The most prevalent four NIS were no appetite (35.3%), dysphagia (29.4%), vomiting (13.2%) and oral pain (12.5%), respectively. All patients in the study were malnutrition. Patients with xerostomia or oral pain had less ONS use days than those without these symptoms. Patients with vomiting (OR 0.09, 95% CI 0.02–0.50) or pain (OR 0.15, 95% CI 0.02–0.89) were less likely to have ONS energy intake ≥400 kcal/day than those without these symptoms after adjusting the confounding factors. In addition, one‐point increase in total NIS score was associated with a lower proportion of ONS energy intake ≥400 kcal/day (OR 0.77, 95% CI 0.59–0.99). Conclusion Xerostomia, oral pain, vomiting and pain should be strengthened and intervened to improve ONS use and nutritional status among HNC patients with malnutrition.

Introduction:Vernonia anthelmintica (L.) Willd. is a traditional treatment for vitiligo in Xinjiang. However, its therapeutic mechanism remains unclear owing to its complex composition and limited research on its chemical profile.Methods: We employed a targeted metabolome approach, combining selective reaction monitoring/multiple response monitoring (SRM/MRM) with high-performance liquid chromatography and MRM mass spectrometry to quantitatively analyze the flavonoid constituents of Vernonia anthelmintica. We also used network pharmacology and molecular docking to identify potential vitiligo-linked compounds and targets of V. anthelmintica seeds. Additionally, we assessed HaCaT cell proliferation by AAPH-induced, alongside changes in SOD activity and MDA content, following treatment with V. anthelmintica components. Finally, flow cytometry was used to detect apoptosis and ROS levels.Results and Discussion: We identified 36 flavonoid compounds in V. anthelmintica seeds, with 14 compounds exhibiting druggability. AKT1, VEGFA, ESR1, PTGS2, and IL2 have been identified as key therapeutic target genes, with PI3K/AKT signaling being an important pathway. Notably, kaempferol, one of the identified compounds, exhibited high expression in network pharmacology analysis. Kaempferol exhibited a strong binding affinity to important targets. Further, kaempferol enhanced HaCaT cell viability, inhibited apoptosis, reduced MDA levels, suppressed ROS activity, and upregulated SOD activity, increase the expression of cellular antioxidant genes, including HO-1, GCLC, GCLM, Nrf2, NQO1 and Keap1, providing significant protection against oxidative stress damage in vitro. Here, we present the first comprehensive study integrating SRM/MRM approaches and network analysis to identify active flavonoid compounds within V. anthelmintica (L.) Willd. Moreover, we revealed that its active ingredient, kaempferol, offers protection against AAPH-induced damage in keratinocytes, highlighting its potential as a clinical resource.

Abstract Background Klebsiella pneumoniae invasion syndrome (KPIS) is a severe multi-site infection that is usually caused by hypervirulent Klebsiella pneumoniae. The bacteria are relatively common in Asian diabetics and can cause organ abscesses or sepsis. When patients develop intracranial infection, the prognosis is poor. After anti-infective treatment, the Klebsiella pneumoniae-induced liver and lung abscesses and pulmonary fungal infection were relieved, but the brain abscesses worsened. Such complex and severe infection cases are rarely reported. Early identification of intracranial infection, selection of antibiotics with high concentrations in cerebrospinal fluid, and active treatment of complications such as diabetes and fungal infection are of great significance for the prognosis of patients. Case presentation A 71-year-old patient diagnosed with liver abscess in another hospital was transferred to our hospital due to a worsening condition. On day 1 (day of admission), the patient was given invasive mechanical ventilation, continuous renal replacement therapy combined with endotoxin adsorption, antimicrobial treatment with imipenem-cilastatin, and percutaneous catheter drainage for liver abscess. Metagenomic next-generation sequencing in bronchoalveolar lavage fluid indicated Klebsiella pneumoniae (K. pneumoniae), Candida albicans, and Aspergillus flavus complex, and no viruses were detected. Blood and pus cultures revealed K. pneumoniae that was sensitive to piperacillin/tazobactam. The anti-infection therapy was adjusted to piperacillin/tazobactam combined with voriconazole. On day 14, a head computed tomography (CT) scan showed no significant changes, and a chest CT scan showed absorption of multiple abscesses in both lungs. The patient was still unconscious. After the endotracheal tube was removed, cranial magnetic resonance imaging (MRI) showed multiple brain abscesses. Finally, his family gave up, and the patient was discharged and died in a local hospital. Conclusion In cases of K. pneumoniae infection, the possibility of intracranial, liver, lung, or other site infections should be considered, and physicians should be vigilant for the occurrence of KPIS. For patients suspected of developing an intracranial infection, cerebrospinal fluid should be tested and cultured as soon as possible, a head MRI should be performed, and antibiotics with high distribution in cerebrospinal fluid should be used early. When patients are complicated with diabetes, in addition to glycemic control, vigilance for concurrent fungal infections is also needed.

Abstract Background The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. Methods This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG‐PS). Survival data were analysed using univariate and multivariate Cox regression analyses. Results The area under the curve, concordance index and survival analysis showed that C‐reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non‐cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08–5.32); high CAR, HR (95% CI) = 2.92 (1.88–4.55); high CRP, HR (95% CI) = 3.12 (2.08–4.67)] indicated a worse prognosis, compared with non‐cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65–3.16); high CAR, HR (95% CI) = 2.36 (1.71–3.25); high CRP, HR (95% CI) = 2.58 (1.85–3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG‐PS 2, HR (95% CI) = 1.61 (1.04–2.50); ECOG‐PS 3/4, HR (95% CI) = 2.91 (1.69–5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG‐PS 2, HR (95% CI) = 1.28 (0.90–1.81); ECOG‐PS 3/4, HR (95% CI) = 2.41 (1.32–4.39]). Patients with CRC cachexia with an ECOG‐PS score of 2 or 3–4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG‐PS score of 0/1 and a low inflammation. Conclusions The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG‐PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG‐PS in patients with CRC cachexia could provide a simple survival prediction.

Abstract Killer meiotic drivers (KMDs) skew allele transmission in their favor by killing meiotic progeny not inheriting the driver allele. Despite their widespread presence in eukaryotes, the molecular mechanisms behind their selfish behavior are poorly understood. In several fission yeast species, single-gene KMDs belonging to the wtf gene family exert selfish killing by expressing a toxin and an antidote through alternative transcription initiation. Here we investigate how the toxin and antidote products of a wtf-family KMD gene can act antagonistically. Both the toxin and the antidote are multi-transmembrane proteins, differing only in their N-terminal cytosolic tails. We find that the antidote employs PY motifs (Leu/Pro-Pro-X-Tyr) in its N-terminal cytosolic tail to bind Rsp5/NEDD4 family ubiquitin ligases, which ubiquitinate the antidote. Mutating PY motifs or attaching a deubiquitinating enzyme transforms the antidote into a toxic protein. Ubiquitination promotes the transport of the antidote from the trans-Golgi network to the endosome, thereby preventing it from causing toxicity. A physical interaction between the antidote and the toxin enables the ubiquitinated antidote to translocate the toxin to the endosome and neutralize its toxicity. We propose that post-translational modification-mediated protein localization and/or activity changes may be a common mechanism governing the antagonistic duality of single-gene KMDs.

Abstract Objectives This study aimed to investigate the effects of a calorie-restricted dietary (CRD) intervention on weight and gut microbiota diversity in obese patients with sleep deprivation (SD). Methods Twenty obese patients were divided into a sleep deprivation group (SD group, n = 10) and a nonsleep deprivation group (NSD group, n = 10), both of which underwent a CRD intervention for 12 weeks. Measurement of anthropometric parameters, biochemical examinations and gut microbiota detection were performed at baseline and at the end of week 12. Mi Smart Bands 1 (Standard Option) were used to monitor sleep and exercise. Results (1) The CRD intervention improved body weight (BW), waist circumference (WC), blood pressure (BP), basal metabolic rate (BMR), body fat content (BFC), and insulin resistance index (HOMA-IR) in all obese patients. (2) In the NSD group, BW, BFC, VFA (visceral fat area), BMR and total cholesterol (TC) were significantly reduced after the CRD intervention (P

The electromagnetic radiation interference mechanism from multiple noise sources on the parallel topology of SiC MOSFET and Si IGBT Inverter is blurred, which will seriously affect the high reliability application of the structure. In order to solve this problem, a topological radiation EMI prediction method is proposed, the method includes the establishment of radiation equivalent models and radiation guidelines, the proposed inverter parallel topology radiation. The modeling method of electromagnetic interference can effectively analyze the influence of radiation interference of SiC and Si devices coupled with each other, and the established PCB radiation near and far field simulation can effectively realize the accurate prediction of radiation interference of inverter parallel topology, and finally the experimental platform of the parallel SiC MOSFET and Si IGBT inverter is built and tested, the test results demonstrate the accuracy of the proposed method.

Obtaining discriminative joint features is crucial for skeleton-based human action recognition. Current models mainly focus on the research of skeleton topology encoding. However, their predefined topology is the same and fixed for all action samples, making it challenging to obtain discriminative joint features. Although some studies have considered the complex non-natural connection relationships between joints, the existing methods cannot fully capture this complexity by using high-order adjacency matrices or adding trainable parameters and instead increase the computation parameters. Therefore, this study constructs a novel adaptive channel-enhanced graph convolution (ACE-GCN) model for human action recognition. The model generates similar and affinity attention maps by encoding channel attention in the input features. These maps are complementarily applied to the input feature map and graph topology, which can realize the refinement of joint features and construct an adaptive and non-shared channel-based adjacency matrix. This method of constructing the adjacency matrix improves the model’s capacity to capture intricate non-natural connections between joints, prevents the accumulation of unnecessary information, and minimizes the number of computational parameters. In addition, integrating the Edgeconv module into a multi-branch aggregation improves the model’s ability to aggregate different scale and temporal features. Ultimately, comprehensive experiments were carried out on NTU-RGB+D 60 and NTU-RGB+D 120, which are two substantial datasets. On the NTU RGB+D 60 dataset, the accuracy of human action recognition was 92% (X-Sub) and 96.3% (X-View). The model achieved an accuracy of 96.6% on the NW-UCLA dataset. The experimental results confirm that the ACE-GCN exhibits superior recognition accuracy and lower computing complexity compared to current methodologies.

E-commerce live streaming has become a lucrative global industry. As the main carrier to convey information in live broadcasting, user-generated content (UGC)—and especially bullet screens—are crucial in influencing users’ purchase intentions. However, the influence of bullet screens’ multidimensional information characteristics on consumers’ decision-making processes requires further exploration. Additionally, most existing studies start with the short-term effects of live product realization, and must address how to enhance customers’ psychological ownership using new means of live streaming marketing to obtain long-term sustainable brand-building effects. This study introduces psychological ownership and the communicative presence as mediating variables based on the theory of elaboration likelihood modeling to explore the mechanism of the influence of UGC’s multidimensional features on viewers’ purchase intentions in live e-commerce broadcasting rooms. We collected 404 valid online questionnaires and tested our hypotheses using structural equation modeling. These findings indicate that UGC emotions, quality, and their interaction significantly and positively affect purchase intentions. Moreover, psychological ownership and the communicative presence mediate UGC’s effect on purchase intentions. These results provide a new perspective for understanding consumer behavior in live e-commerce to improve marketing effectiveness of e-commerce live streaming platforms.

Previous studies have shown that the elevated levels of circulating branched-chain amino acids (BCAAs) are associated with the development of insulin resistance and its complications, including obesity, type 2 diabetes, cardiovascular disease and some cancers. However, animal models that can mimic the metabolic state of chronically elevated BCAAs in humans are rare. Therefore, the aim of this study was to establish the above animal model and analyse the metabolic changes associated with high BCAA levels. Sixteen 8-week-old Sprague–Dawley (SD) rats were randomly divided into two groups and given either a high fructose diet or a normal diet. BCAA levels as well as blood glucose and lipid levels were measured at different time points of feeding. The mRNA expression levels of two key enzymes of BCAA catabolism, ACAD (acyl-CoA de hydrogenase) and BCKDH (branched-chain α-keto acid dehydrogenase), were measured by qPCR, and the protein expression levels of these two enzymes were analysed by immunoh istochemistry. Finally, the metabolite expression differences between the two groups were analysed by Q300 metabolomics technology. Our study confirms that defects in the catabolic pathways of BCAAs lead to increased levels of circulating BCAAs, resulting in disorders of glucose and lipid metabolism characterized by insulin resistance by affecting metabolic pathways associated with amino acids and bile acids.

Aims: Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action. Main methods: This study utilized male and female systemic BMX knockout (BMX−/−) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level. Key findings: Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway. Significance: Our investigation showed that BMX−/− reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.

Summary: The serine/threonine protein phosphatase family involves series of cellular processes, such as pre-mRNA splicing. The function of one of its members, protein phosphatase, Mg2+/Mn2+ dependent 1G (PPM1G), remains unclear in hepatocellular carcinoma (HCC). Our results demonstrated that PPM1G was significantly overexpressed in HCC cells and tumor tissues compared with the normal liver tissues at both protein and RNA levels. High PPM1G expression is associated with shorter overall survival (p

IntroductionEpstein-Barr virus (EBV) is a highly dangerous virus that is globally prevalent and closely linked to the development of nasopharyngeal cancer (NPC). Plasma EBV DNA analysis is an effective strategy for early detection, prognostication and monitoring of treatment response of NPC.MethodsHere, we present a novel molecular diagnostic technique termed EBV-MCDA-LFB, which integrates multiple cross displacement amplification (MCDA) with nanoparticle-based lateral flow (LFB) to enable simple, rapid and specific detection of EBV. In the EBV-MCDA-LFB system, a set of 10 primers was designed for rapidly amplifying the highly conserved tandem repeat BamHI-W region of the EBV genome. Subsequently, the LFB facilitate direct assay reading, eliminating the use of extra instruments and reagents.ResultsThe outcomes showed that the 65°C within 40 minutes was the optimal reaction setting for the EBV-MCDA system. The sensitivity of EBV-MCDA-LFB assay reached 7 copies per reaction when using EBV recombinant plasmid, and it showed 100% specificity without any cross-reactivity with other pathogens. The feasibility of the EBV-MCDA-LFB method for EBV detection was successfully validated by 49 clinical plasma samples. The complete detection process, consisting of rapid template extraction (15 minutes), MCDA reaction (65°C for 40 minutes), and LFB result reading (2 minutes), can be finalized within a 60-minutes duration.DiscussionEBV-MCDA-LFB assay designed here is a fast, extremely sensitive and specific technique for detecting EBV in field and at the point-of-care (PoC), which is especially beneficial for countries and regions with a high prevalence of the disease and limited economic resources.

The ultra wideband (UWB) radar detection technology can achieve mine human target detection for drilling rescue. However, UWB electromagnetic waves are susceptible to the complex environment of catastrophic mines. The UWB radar echo signals are susceptible to the background clutter and environmental noise of catastrophic mines. It is difficult to achieve precise detection of human targets in catastrophic mines. In order to solve the above problems, the underground target detection scenarios and human target detection principles based on UWB radar are introduced. The research status of UWB electromagnetic wave characteristics and UWB echo noise filtering methods are analyzed. The existing problems are summarized as following points. ① The propagation characteristics of UWB electromagnetic waves in the complex environment of catastrophic mines require in-depth research. ② The reason for the generation of background clutter is not yet clear. There is limited research on the filtering technology of background clutter and environmental noise in catastrophic mines. ③ The UWB radar human target detection technology for drilling rescue still needs to be improved. In response to the shortcomings of existing technologies, the development trend of UWB radar underground human target detection technology for drilling rescue is prospected. ① It is suggested to do in-depth research on the sensitivity of key characterization parameters of UWB electromagnetic wave penetration transmission to complex underground environmental characteristics. ② It is suggested to construct methods for filtering background clutter and environmental noise suitable for catastrophic mines. ③ It is suggested to deeply optimize UWB radar human target detection technology for drilling rescue.

Abstract Background Cosmc (C1GalT1C1) mutation could cause aberrant O-glycosylation and result in expression of Tn antigen on the surface of tumor cells (Tn+ cells), which is associated with the metastasis and prognosis of cancer progression. Mesenchymal stem cells (MSCs) could participate in immunoregulation, tissue damage repair, and tumor inhibition and be seen as an ideal candidate for tumor therapy due to their inherent capacity to migrate to tumor sites. However, their therapeutic effectiveness in different tumors is inconsistent and still controversial. Of note, emerging data reveal that side population (SP) cells have a stronger multilineage developmental potential than main population cells and can function as stem/progenitor cells. The effect of SP cells derived from MSCs on the biological behaviors and the O-glycosylation status of tumor cells remains unclear. Methods SP cells were isolated from human umbilical cord MSCs (hUCMSCs) and human placenta MSCs (hPMSCs). Tn+ cells (LS174T-Tn+ and HT-29-Tn+ cells) and matching Tn− cells (LS174T-Tn− and HT-29-Tn− cells) were isolated from human colorectal cancer cell (CRC) lines LS174T and HT-29 by immune magnetic beads. The proliferation, migration, apoptosis, Tn antigen expression, and O-glycome in Tn+ and Tn− CRC cells before and after co-cultured with SP-MSCs were detected using real-time cell Analysis (RTCA), flow cytometry (FCM), and cellular O-glycome reporter/amplification (CORA), respectively. Cosmc protein and O-glycosyltransferase (T-synthase and C3GnT) activity in CRC cells were, respectively, assessed using western blotting and fluorescence method. Results Both SP cells derived from hUCMSCs and hPMSCs could inhibit proliferation and migration, promote apoptosis of CRC cells, significantly reduce Tn antigen expression on Tn+ CRC cells, generate new core 1-, 2-, and 3-derived O-glycans, increase T-synthase and C3GnT activity, and elevate the levels of Cosmc and T-synthase protein. Conclusion SP-hUCMSCs and SP-hPMSCs could inhibit proliferation and migration and promote apoptosis of Tn+ CRC cells via increasing O-glycosyltransferase activity to modify O-glycosylation status, which further adds a new dimension to the treatment of CRC.

Considering the inherent laws and logical relationships between disasters and poverty, the combination of poverty alleviation relocation (PAR) and earthquake reconstruction relocation (ERR) is valuable both theoretically and practically. This study compared PAR and ERR projects on a systematic basis in terms of implementation area, mode adoption, construction content, public engagement, and challenges. Moreover, four common types of villages (e.g., enclave, adjacent, centralized, and infill) and the two resident groups of the re-settler and local groups were recognized. Regarding the social restructuring after relocation, the performance of the double-directional degree of social isolation (SO) and spatial isolation (SP) between the two resident groups were evaluated and compared in types, which helps planners predict and clarify the social impact of the chosen type. The underlying social and spatial reasons affecting the social integration were explained to propose the corresponding planning measures for social integration promotion.

C2H4 is used as an indicator gas to evaluate the spontaneous combustion process of coal, and the adsorption of C2H4 by coal will cause the decrease of C2H4 gas volume fraction in mine air, which in turn affects the accuracy of the assessment of the spontaneous combustion process of coal. In order to reveal the microscopic mechanism of C2H4 adsorption in bituminous coal, a molecular model of Wiser bituminous coal was constructed, and the adsorption process of C2H4 in the molecular model of bituminous coal at temperature of 293.15-313.15 K and pressure of 0.1-3 MPa was simulated using Monte Carlo method, and the changes of adsorption heat, adsorption potential energy and adsorption entropy during the adsorption process were analyzed. The results showed that the adsorption of C2H4 in bituminous coal molecules first increased rapidly with increasing pressure and then leveled off; the higher the temperature, the lower the adsorption of C2H4 when the pressure was the same; Langmuir-Freundlich model has the best fitting effect on C2H4 adsorption process, and the maximum adsorption a of C2H4 decreases with increasing temperature; the average heat of adsorption of C2H4 under different temperature conditions is 35.29-37.65 kJ/mol, indicating that the adsorption of C2H4 in bituminous coal is physical adsorption; the adsorption potential energy and entropy of C2H4 decreased

Obtaining the position of underground trapped personnel quickly and precisely is a key issue for life information detection in the early stage of borehole rescue. In the process of vertical drilling and rescue, due to the collapse of the roadway in the detection area or the displacement of the final hole position, it is impossible to obtain the position of the trapped personnel quickly and accurately. It delays the golden time of rescue and affects the safety of personnel. Through conducting a UWB radar wave transmission attenuation study, a rescue plan can be quickly formulated for on-site rescue commanders. This paper analyzes the current situation and demand of UWB radar wave application in mine borehold rescue. Combined with the background of mine borehold rescue, it is pointed out the attenuation law of UWB radar wave transmission. The study analyzes the influence of the characteristic parameters of the medium on the attenuation of radar wave transmission from the perspective of anisotropy of the medium. The influence of dielectric parameters on radar wave transmission attenuation is analyzed from four aspects: dielectric constant, conductivity, magnetic permeability and spatiotemporal variation. The influence of radar characteristic parameters on radar wave transmission attenuation is analyzed from two aspects: radar frequency and polarization. Based on the above analysis, it is pointed out that there are few studies on the simultaneous penetration of UWB radar waves through anisotropic media such as coal and rock masses and the mechanism of media propagation and attenuation. There are few theories and experiments on UWB radar wave transmission attenuation in complex and changeable underground or simulating disaster environments. And there are few summaries of relevant laws. The mapping relationship database between key parameters and influencing factors of UWB radar waves is not yet complete. The key technologies to be studied in the future are given as follows. It is suggested to conduct research on anisotropic media such as coal and rock masses at both macro and micro levels. It is suggested to establish an experimental simulation system for radar wave transmission attenuation under catastrophic environmental conditions. It is suggested to add research on UWB radar signal propagation characteristics and channel modeling numerical simulation in unstructured environments after disasters.

Abstract Background Sepsis can result in acute lung injury (ALI). Studies have shown that pharmacological inhibition of ferroptosis can treat ALI. However, the regulatory mechanisms of ferroptosis in sepsis-induced ALI remain unclear. Methods Transcriptome sequencing was performed on lung tissue samples from 10 sepsis-induced mouse models of ALI and 10 control mice. After quality control measures, clean data were used to screen for differentially expressed genes (DEGs) between the groups. The DEGs were then overlapped with ferroptosis-related genes (FRGs) to obtain ferroptosis-related DEGs (FR-DEGs). Subsequently, least absolute shrinkage and selection operator (Lasso) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were used to obtain key genes. In addition, Ingenuity Pathway Analysis (IPA) was employed to explore the disease, function, and canonical pathways related to the key genes. Gene set enrichment analysis (GSEA) was used to investigate the functions of the key genes, and regulatory miRNAs of key genes were predicted using the NetworkAnalyst and StarBase databases. Finally, the expression of key genes was validated with the GSE165226 and GSE168796 datasets sourced from the Gene Expression Omnibus (GEO) database and using quantitative real-time polymerase chain reaction (qRT-PCR). Results Thirty-three FR-DEGs were identified between 1843 DEGs and 259 FRGs. Three key genes, Ncf2, Steap3, and Gclc, were identified based on diagnostic models established by the two machine learning methods. They are mainly involved in infection, immunity, and apoptosis, including lymphatic system cell migration and lymphocyte and T cell responses. Additionally, the GSEA suggested that Ncf2 and Steap3 were similarly enriched in mRNA processing, response to peptides, and leukocyte differentiation. Furthermore, a key gene-miRNA network including 2 key genes (Steap3 and Gclc) and 122 miRNAs, and a gene-miRNA network with 1 key gene (Steap3) and 3 miRNAs were constructed using NetworkAnalyst and StarBase, respectively. Both databases predicted that mmu-miR-15a-5p was the target miRNA of Steap3. Finally, Ncf2 expression was validated using both datasets and qRT-PCR, and Steap3 was validated using GSE165226 and qRT-PCR. Conclusions This study identified two FR-DEGs (Ncf2 and Steap3) associated with sepsis-induced ALI via transcriptome analyses, as well as their functional and metabolic pathways.

(1) Background and Aims: Manure is an important source of nutrients for plants, and organic substrate, as an effective soil amendment substrate, is a common material for maintaining soil health in the context of agricultural intensification. The use of organic fertilizers to meet the nutrient requirements of crops and to improve soil structure is a natural choice for sustainable agriculture. The high cost of chemical fertilizers and their overuse can lead to agricultural pollution, so farmers’ awareness of organic farming is increasing, which is helping to drive agriculture in a more environmentally friendly and sustainable direction. (2) Methods: In a fertilization experiment conducted on 38-year-old ‘Changfu No.2’ apple trees, four different fertilization treatments were designed to assess their effects on soil fertility, fruit quality, and apple yield. These treatments included no fertilizer as a control (CK); chemical fertilizer combined with organic substrate (NPK + O); chemical fertilizer combined with sheep manure (NPK + SM); and a combination of chemical fertilizer, organic substrate, and sheep manure (NPK + O + SM). Principal component analysis (PCA) was used to comprehensively evaluate soil fertility, apple yield, and quality under these treatments. (3) Results: The NPK + O + SM treatment significantly improved soil fertility and apple yield compared to the other treatments. It provided comprehensive nutrition, meeting the diverse needs of plant growth. The slow-release properties of the organic substrate combined with the immediate nutrient supply from the sheep manure ensured stable nutrition throughout the growing season. This mixed fertilizer also improved soil biological activity. (4) Conclusion: The fertilization strategy combining organic substrate and sheep manure (NPK + O + SM) is highly effective in improving soil fertility, fruit quality, and apple yield, thus supporting sustainable agricultural practices.

A high-efficiency nickel-doped porous biochar (PCNi3) has been successfully synthesized from chestnut shell waste via a two-step chemical activation treatment with H3PO4. The influences of microstructure, surface morphology, elemental composition, surface functional groups, specific surface area, porosity, pore-size distribution, and chemical properties of the surface state on the removal of Cr (VI) from water were thoroughly investigated by using XRD, FESEM, FTIR, Raman, BET, and XPS testing methods, N2 adsorption, and XPS testing techniques respectively. The results indicate that the treatment of H3PO4 activation and nickel doping can effectively improve microstructure characteristics, thus promoting Cr (VI) adsorption capacity. The effects of initial solution pH, solution concentration, time, and temperature on remediation are revealed. The Cr (VI) uptake experiments imply that the adsorption curves of PCNi3 fit well with the Freundlich model, the pseudo-second-order kinetic model, and the Elovich model. The adsorption process of PCNi3 can be regarded as a spontaneous endothermic reaction limited by diffusion among particles and porosity. The adsorption mechanisms of PCNi3 are ion exchange, complexation, electrostatic adsorption, and coprecipitation with the assistance of surface active sites, porosity, Ni0 particles, and Ni7P3. With these advantages, PCNi3 reveals an extraordinary Cr (VI) removal capacity and a strong ability to reduce Cr (VI) to Cr (III).

Abstract Ni‐rich layered oxides are considered as promising cathodes for next‐generation lithium‐ion batteries. However, they still suffer microstructure and surface instability particularly under high operating voltage, leading to rapid capacity fading and battery failure. In this context, Ni‐rich layered cathodes (LiNixCoyMn1−x−yO2; LNCM) with aluminum and indium co‐modified crystal and surface structures are developed by a simple one‐pot calcination approach. Battery tests show that the Al and In co‐modified LNCM electrodes demonstrate remarkably enhanced rate capability and cycling stability compared with the pristine LNCM, Al‐doped LNCM, and In‐modified LNCM counterparts. Further characterizations reveal a simultaneous suppression of cracking and resistive film growth. The improved microstructural and surface stability originate from the synergistic functions of Al and In co‐modification. The incorporation of Al3+ into transition metal slab significantly reduces the Li+/Ni2+ antisite, which noticeably mitigates the undesired layer to rock‐salt phase transformation. The In3+ dopant dispersed in Li interslab can dissipate the anisotropic lattice strain, enabling greatly improved reversibility of H2↔H3 phase transition occurred in delithiation‐lithiation processes. Meanwhile, the synchronously formed LiInO2 adherent coatings deplete lithium residues, facilitate lithium‐ion transfer, and resist electrolyte corrosion. Microstructure and surface engineering through Al and In co‐modification offer a promising design strategy for Ni‐rich layered cathodes.

This research aimed to examine the mediating effect of intrusive imagery and fear of negative evaluation on the connection between body dissatisfaction and smartphone addiction. 5,909 participants were included in the research, with 53.8% of the sample being female. The average age of the participants was 19.87 years, and their ages ranged from 18 to 32 years. All individuals who were recruited for the study successfully finished the Satisfaction and Dissatisfaction with Body Parts Scale, the Smartphone Addiction Scale, the Intrusive Imagery Scale, and the Fear of Negative Evaluation Scale. Mediational analysis indicated that, with age, gender and body mass index under control, body dissatisfaction was linked to smartphone addiction via (1) the mediating role of intrusive imagery, (2) the mediating role of fear of negative evaluation, and (3) the serial mediating role of intrusive imagery and fear of negative evaluation. Our study for the first time advanced our understanding that intrusive imagery and fear of negative evaluation could be serial mediators of the relationship between body dissatisfaction and smartphone addiction. However, the cross-sectional design prevented us from establishing causality between these variables, which could be better examined in future longitudinal studies.

In recent years, the Alzheimer’s disease (AD) epidemic has become one of the largest global healthcare crises. Besides, the available systemic therapies for AD are still inadequate. Due to the insufficient therapeutic options, new treatment strategies are urgently needed to achieve a satisfactory therapeutic effect. Marine bio-resources have been accepted as one of the most economically viable and sustainable sources with potential applications for drug discovery and development. In this study, a marine cyanobacteria–Synechococcus sp. XM-24 was selected as the object of research, to systematically investigate its therapeutic potential mechanisms for AD. The major active compounds derived from the Synechococcus sp. biomass were identified via pyrolysis-gas chromatography-mass spectrometry (GC-MS), and 22 compounds were identified in this strain. The most abundant chemical compounds was (E)-octadec-11-enoic acid, with the peak area of 30.6%. Follow by tridecanoic acid, 12-methyl- and hexadecanoic acid, with a peak area of 23.26% and 18.23%, respectively. GC-MS analysis also identified indolizine, isoquinoline, 3,4-dihydro- and Phthalazine, 1-methyl-, as well as alkene and alkane from the strain. After the chemical toxicity test, 10 compounds were finally collected to do the further analysis. Then, network pharmacology and molecular docking were adopted to systematically study the potential anti-AD mechanism of these compounds. Based on the analysis, the 10 Synechococcus-derived active compounds could interact with 128 related anti-AD targets. Among them, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA) and mitogen-activated protein kinase 3 (MAPK3) were the major targets. Furthermore, the compounds N-capric acid isopropyl ester, (E)-octadec-11-enoic acid, and 2H-Pyran-2,4(3H)-dione, dihydro-6-methyl- obtained higher degrees in the compounds-intersection targets network analysis, indicating these compounds may play more important role in the process of anti-AD. In addition, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these active compounds exert the anti-AD effects mainly through PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction and ras signaling pathway. Our study identified Synechococcus-derived bioactive compounds have the potential for application to AD by targeting multiple targets and related pathways, which will provide a foundation for future research on applications of marine cyanobacteria in the functional drug industry.

ObjectiveOur previous studies have demonstrated that Plasmodium immunotherapy (infection) has antitumor effects in mice. However, as a new form of immunotherapy, this therapy has a weakness: its specific killing effect on tumor cells is relatively weak. Therefore, we tested whether Plasmodium immunotherapy combined with gemcitabine (Gem), a representative chemotherapy drug, has synergistic antitumor effects.MethodsWe designed subcutaneously and intravenously implanted murine Lewis lung cancer (LLC) models to test the antitumor effect of Plasmodium chabaudi ASS (Pc) infection in combination with Gem treatment and explored its underlying mechanisms.ResultsWe found that both Pc infection alone and Gem treatment alone significantly inhibited tumor growth in the subcutaneous model, and combination therapy was more effective than either monotherapy. Monotherapy only tended to prolong the survival of tumor-bearing mice, while the combination therapy significantly extended the survival of mice, indicating a significant synergistic effect of the combination. In the mechanistic experiments, we found that the combination therapy significantly upregulated E-cadherin and downregulated Snail protein expression levels, thus inhibiting epithelial-mesenchymal transition (EMT) of tumor cells, which may be due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β signaling pathway.ConclusionThe combination of Pc and Gem plays a synergistic role in inhibiting tumor growth and metastasis, and prolonging mice survival in murine lung cancer models. These effects are partially attributed to the inhibition of EMT of tumor cells, which is potentially due to the blockade of CXCR2/TGF-β-mediated PI3K/Akt/GSK-3β/Snail signaling pathway. The clinical transformation of Plasmodium immunotherapy combined with Gem for lung cancer is worthy of expectation.

Abstract Background The Chinese government stipulates all food for special medical purposes (FSMP) designed for specific diseases to be tested in clinical trials before approving it for registration. The process of developing core outcome sets (COSs), the minimum sets of outcomes supposed to be measured and reported, provides an economical and practical option for stakeholders to communicate and cooperate in conducting clinical trials as well as in reporting FSMP outcomes. This study uses type 2 diabetes mellitus (T2DM) as an example to develop COS for clinical trials of FSMP. Methods The COS for FSMP-T2DM will be divided into 3 phases and developed following COS-STAP and COS-STAD: (1) Generate a list of relevant outcomes identified from a systematic review, in which information sources will mainly include published studies, regulatory documentation, and qualitative interviews of stakeholders. The identified outcomes will be categorized using a conceptual framework and formatted into the first round of the Delphi survey questionnaire items. (2) At least 2 rounds of Delphi surveys will be performed among stakeholders to create the COS for FSMP-T2DM. Patients, clinical dietitians, physicians, COS researchers, journal editors, FSMP manufacturers, and regulatory representatives will be invited to score each outcome from aspects of importance. (3) Hold a face-to-face or online consensus meeting to refine the content of the COS for FSMP-T2DM. Key stakeholders will be invited to attend the meeting to discuss and agree on the final COS. Discussion We have prepared an alternative solution of the Likert scale selection, Delphi survey rounds, scoring group, and consensus definitions in case of an unexpected situation. Trial registration COMET (1547). Registered on March 23, 2020.

Abstract To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.

Endothelin receptors (ETAR and ETBR) are critical for vasoregulation and are targets for cardiovascular diseases treatment. Here, the authors offer a structural basis for peptide recognition selectivity and activation of both endothelin receptors.

Abstract Isorhamnetin (ISO) is a methylated flavonol present in the leaves, flowers, and fruits of many plants with antitumour, anti-inflammatory, antioxidant, and anti-apoptotic properties. ISO has been suggested as the active substance in Vernonia anthelmintica (L.) to treat vitiligo. However, the mechanisms underlying its effects remain unclear. In this study, human keratinocytes (HaCaT cells) were pre-treated with or without ISO and then stimulated with hydrogen peroxide (H2O2) to generate oxidative damage. Pre-treatment with ISO increased HaCaT cell viability, reduced malondialdehyde content, and enhanced superoxide dismutase activity, resulting in a reduction in the loss of mitochondrial membrane potential, improved cell morphological damage, and apoptosis inhibition. Furthermore, we identified 51 significantly dysregulated differentially expressed genes (DEGs) of HaCaT cells treated with ISO using RNA-sequencing. Enrichment analysis using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases indicated that the protective effect of ISO could be related to its effects on the Wnt signalling pathway. Our study provides novel insights into key gene regulation in the progression of oxidative damage and the mechanisms of action of ISO.

Teratozoospermia is a rare disease associated with male infertility. Several recurrent genetic mutations have been reported to be associated with abnormal sperm morphology, but the genetic basis of tapered-head sperm is not well understood. In this study, whole-exome sequencing (WES) identified a homozygous WD repeat domain 12 (WDR12; p.Ser162Ala/c.484T>G) variant in an infertile patient with tapered-head spermatozoa from a consanguineous Chinese family. Bioinformatic analysis predicted this mutation to be a pathogenic variant. To verify the effect of this variant, we analyzed WDR12 protein expression in spermatozoa of the patient and a control individual, as well as in the 293T cell line, by Western blot analysis, and found that WDR12 expression was significantly downregulated. To understand the role of normal WDR12, we evaluated its mRNA and protein expression in mice at different ages. We observed that WDR12 expression was increased in pachytene spermatocytes, with intense staining visible in round spermatid nuclei. Based on these results, the data suggest that the rare biallelic pathogenic missense variant (p.Ser162Ala/c.484T>G) in the WDR12 gene is associated with tapered-head spermatozoa. In addition, after intracytoplasmic sperm injection (ICSI), a successful pregnancy was achieved. This finding indicates that infertility associated with this WDR12 homozygous mutation can be overcome by ICSI. The present results may provide novel insights into understanding the molecular mechanisms of male infertility.

In view of the limitations of triangular intuitionistic fuzzy numbers (TIFNs) in value selection and application, the purpose of this paper is to redefine and demonstrate the algorithm, expectation function and distance measure of TIFNs, and to put forward a new theory of triangular intuitionistic fuzzy sets (TIFSs). The new theory of TIFSs is then applied to the field of two-sided matching decision-making. To solve the two-sided matching problem based on TIFSs, the agent behavior factors of both sides are calculated by this theory. On this basis, a multi-objective matching model under TIFS preference is constructed. Furthermore, the optimal matching scheme is obtained by transforming and solving the model according to the expected score, the linear weighting and the algorithm of “being as good as possible”. Finally, the practicability of the proposed two-sided matching method is verified by a transaction matching example. The novelty and key idea of the proposed method are as follows: (1) it combines the idea of closeness in TOPSIS method and the expected score in the new theory of TIFSs to measure the behavior factors of two-sided agents; (2) it builds a two-sided matching model considering the behavior factors under the preference of TIFSs; (3) according to the idea of “being as good as possible”, a novel algorithm for solving the two-sided matching model under TIFS preference is proposed. The major conclusion and advantage of this paper is that the obtained BM scheme using the proposed method can reflect agent behavior factors and maximize agents’ satisfaction as much as possible.