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Abstract Purpose This study aims to investigate the risk factors for lymph node metastasis (LNM) in synchronous multiple primary lung cancer (sMPLC) using clinical and CT features, and to offer guidance for preoperative LNM prediction and lymph node (LN) resection strategy. Materials and methods A retrospective analysis was conducted on the clinical data and CT features of patients diagnosed with sMPLC at the Third Affiliated Hospital of Kunming Medical University from January 1, 2018 to December 31, 2022. Patients were classified into two groups: the LNM group and the non-LNM (n-LNM) group. The study utilized univariate analysis to examine the disparities in clinical data and CT features between the two groups. Additionally, multivariate analysis was employed to discover the independent risk variables for LNM. The diagnostic efficacy of various parameters was evaluated using the receiver operating characteristic (ROC) curve. Results Among the 688 patients included in this study, 59 exhibited LNM. Univariate analysis revealed significant differences between the LNM and n-LNM groups in terms of gender, smoking history, CYFRA21-1 level, CEA level, NSE level, lesion type, total lesion diameter, main lesion diameter, spiculation sign, lobulation sign, cavity sign, and pleural traction sign. Logistic regression identified CEA level (OR = 1.042, 95%CI: 1.009-1.075), lesion type (OR = 9.683, 95%CI: 3.485-26.902), and main lesion diameter (OR = 1.677, 95%CI: 1.347-2.089) as independent predictors of LNM. The regression equation for the joint prediction was as follows: logit(p)= -7.569+0.041*CEA level +2.270* lesion type +0.517* main lesion diameter.ROC curve analysis showed that the AUC for CEA level was 0.765 (95% CI, 0.694–0.836), for lesion type was 0.794 (95% CI, 0.751–0.838), for main lesion diameter was 0.830 (95% CI, 0.784–0.875), and for the combine predict model was 0.895 (95% CI, 0.863–0.928). Conclusion The combination of clinical and imaging features can better predict the status of LNM of sMPLC, and the prediction efficiency is significantly higher than that of each factor alone, and can provide a basis for lymph node management decision.

Abstract Background The maternal gut microbiome is the direct and important source of early colonization and development of the neonatal gut microbiome. However, differences in unique and shared features between mothers with different physiological phenotypes and their newborns still lack exhaustive investigation. Here, using a cow-to-calf model, a comprehensive investigation was conducted to elucidate the pattern and characterization of microbial transfer from the maternal source to the offspring. Results The microbiota in the rumen and feces of dairy cows were divided into two clusters via enterotype analysis. The cows from the enterotype distinguished by Prevotella in the rumen had better production performance, whereas no difference was observed in the cows classified by feces enterotype. Furthermore, through a pairwise combination of fecal and ruminal enterotypes, we screened a group of dairy cows with excellent phenotypes. The gastrointestinal microbiomes of cows with different phenotypes and their offspring differed significantly. The rumen was a more important microbial source for meconium than feces. Transmission of beneficial bacteria from mother to offspring was observed. Additionally, the meconium inherits advantageous metabolic functions of the rumen. The resistome features of the rumen, feces, and meconium were consistent, and resistome abundance from cows to calves showed an expanding trend. The interaction between antibiotic-resistance genes and mobile genetic elements from the rumen to meconium was the most remarkable. The diversity of core metabolites from cows to calves was stable and not affected by differences in phenotypes. However, the abundance of specific metabolites varied greatly. Conclusions Our study demonstrates the microbial taxa, metabolic function, and resistome characteristics of maternal and neonatal microbiomes, and reveals the potential vertical transmission of the microbiome from a cow-to-calf model. These findings provide new insights into the transgenerational transmission pattern of the microbiome. Video Abstract

Abstract Face shape priors such as landmarks, heatmaps, and parsing maps are widely used to improve face super resolution (SR). It is observed that face priors provide locations of high‐frequency details in key facial areas such as the eyes and mouth. However, existing methods fail to effectively exploit the high‐frequency information by using the priors as either constraints or inputs. This paper proposes a novel high frequency highway (H2F) framework to better utilize prior information for face SR, which dynamically decomposes the final SR face into a coarse SR face and a high frequency (HF) face. The coarse SR face is reconstructed from a low‐resolution face via a texture branch, using only pixel‐wise reconstruction loss. Meanwhile, the HF face is directly generated from face priors via an HF branch that employs the proposed inception–hourglass model. As a result, H2F allows the face priors to have a direct impact on the SR face by adding the outputs of both branches as the final result and provides an extra face editing function. Extensive experiments show that H2F significantly outperforms state‐of‐the‐art face SR methods, is general for different texture branch models and face priors, and is robust to dataset mismatch and pose variations.

Abstract Background Accumulating evidence shows that free fatty acids (FFA) are associated with gestational diabetes mellitus (GDM). However, most of the studies focus on a few specific types of FFA, such as α-linolenic acid (C18:3n3) and Arachidonic acid (C20:4n6) or a total level of FFA. Objective This study aimed to test the association between a variety of FFAs during the first trimester and the risk of GDM. Methods The participants came from the Zhoushan Pregnant Women Cohort (ZWPC). A 1:2 nested case-control study was conducted: fifty mothers with GDM were matched with 100 mothers without GDM by age, pre-pregnancy body mass index (BMI), month of oral glucose tolerance test (OGTT) and parity. Thirty-seven FFAs (including 17 saturated fatty acids (SFA), 8 monounsaturated fatty acids (MUFA), 10 polyunsaturated fatty acids (PUFA) and 2 trans fatty acids (TFA)) in maternal plasma during the first trimester were tested by Gas Chromatography–Mass Spectrometry (GC-MS). Conditional logistic regression models were performed to assess the associations of FFA with the risk of GDM. Results Nine FFAs were respectively associated with an increased risk of GDM (P

Abstract The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 μmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80–1.40), 1.24 (95% CI 0.89–1.74) and 1.47 (95% CI 1.04–2.08) fold risk for proteinuria with a trend test P trend

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

ABSTRACTThe role of ferroptosis-associated gene SLC7A11 in esophageal cancer progression is largely unknown, therefore, the effects of blocking SLC7A11 on esophageal squamous cell carcinoma (ESCC) cells are evaluated. Results showed that SLC7A11 was overexpressed in ESCC tissues both in mRNA and protein levels. Blocking SLC7A11 using Erastin suppressed the proliferation and colony formation of ESCC cells, decreased cellular ATP levels, and improved ROS production. Sixty-three SLC7A11-binding proteins were identified using the IP-MS method, and these proteins were enriched in four signaling pathways, including spliceosome, ribosome, huntington disease, and diabetic cardiomyopathy. The deubiquitinase inhibitors PR-619, GRL0617, and P 22077 could reduce at least 40% protein expression level of SLC7A11 in ESCC cells, and PR-619 and GRL0617 exhibited suppressive effects on the cell viability and colony formation ability of KYSE30 cells, respectively. Erastin downregulated GPX4 and DHODH and also reduced the levels of β-catenin, p-STAT3, and IL-6 in ESCC cells. In conclusion, SLC7A11 was overexpressed in ESCC, and blocking SLC7A11 using Erastin mitigated malignant phenotypes of ESCC cells and downregulated key ferroptosis-associated molecules GPX4 and DHODH. The therapeutic potential of targeting SLC7A11 should be further evaluated in the future.

Objectives: This study’s objectives were to explore the potential of wideband acoustic immittance (WAI) as a diagnostic tool, examining its accuracy and efficiency in pediatric audiology. Methods: A narrative review of the contemporary literature was conducted, focusing on studies that assessed the use of WAI in diagnosing pediatric auditory conditions. Key variables such as diagnostic accuracy, efficiency, and clinical outcomes were considered. Results: This review highlighted that WAI offers a broader range of test frequencies and more comprehensive diagnostic information compared with traditional tympanometry. The studies indicated that WAI has the potential to improve diagnostic accuracy and efficiency in pediatric audiology. Distinct patterns of wideband absorbance were identified, enabling more detailed and accurate diagnostic evaluations. Conclusions: WAI shows substantial potential as a diagnostic tool in pediatric audiology, offering improvements in diagnostic accuracy and efficiency over traditional methods. While the initial findings are promising, further research is needed to fully understand its applicability and benefits across different pediatric populations. Future studies should aim to validate the clinical utility of WAI to ensure its widespread adoption in pediatric audiological assessments.

Abstract Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is frequently located in the pharyngeal crypts. This is a highly aggressive malignant tumor that frequently leads to distant metastases in many cases and poses a significant public health challenge, particularly in certain geographic regions globally. This review discusses the epidemiology, risk factors, diagnosis, and treatment options for NPC, emphasizing the importance of early detection and comprehensive management strategies in improving patient outcomes. Moreover, the article explores the intricate mechanisms that cause NPC. Comprehending these fundamental principles can assist in creating specific prevention and therapy approaches for NPC. Recent advances in diagnostic methods, including imaging tests and molecular biomarkers, are emphasized to improve early diagnosis and individualized treatment strategies for individuals with NPC. The review also explores the most recent advancements in treating early-stage (stage I and II) NPC patients, highlighting the changing landscape of individualized therapy approaches for this particular set of patients.

Abstract Objectives Existing data regarding the risk of COVID‐19 infection and its effects on seizure control in patients with epilepsy (PWE) are inconclusive. Our research aims to investigate the PWE who are susceptible to COVID‐19 and what factors contribute to seizure exacerbation. Methods From Dec 28, 2022 to Feb 19, 2023, a cross‐sectional questionnaire survey among adult PWE was conducted. The demographics, epilepsy‐related information, COVID‐19‐related variables, and seizure outcomes after COVID‐19 infection were collected. Multivariate logistic analyses were performed to determine the risk factors associated with COVID‐19 infection and exacerbated seizures. Results Of 1557 PWE, 829 (53.2%) were infected with COVID‐19 and 136 (16.4%) developed seizure exacerbation after COVID‐19 infection. Overweight/obesity (OR 1.372, 95% CI 1.075–1.753, p = 0.011), immunocompromised (OR 3.301, 95% CI 1.093–9.974, p = 0.031), active epilepsy (OR 1.700, 95% CI 1.378–2.097, p

Synthetic Aperture Radar (SAR) has the advantage of noncontact monitoring around the clock and is an important tool for closed space security monitoring. However, when SAR is employed in complex closed spaces, it is susceptible to multipath effects, resulting in a considerable number of virtual images in the image, which has a detrimental impact on interpretation. Existing methods require scene priors for multipath estimation or subaperture weighted fusion to suppress multipath; however, accurately distinguishing multipath virtual images from target images is challenging. This paper proposes a novel multi-angle dual-layer deviation measurement method that effectively distinguishes multipath virtual images from targets. The proposed method employs a large viewing angle difference to conduct multi-angle observation of the target scene, capitalizing on the fact that the position of the multipath virtual image varies with the observation angle, whereas the actual target position remains constant; this is followed by applying a dual-layer deviation measurement algorithm. The algorithm calculates the deviation between the sequence amplitude value and mean twice based on the sparsity of multipath in the multiangle sequence. The proposed method accurately detects and removes sparse and unstable multipath components, whereas the remaining stable components are averaged. This effectively suppresses multipath while retaining target information. Finally, the simulation and actual millimeter wave radar data processing verified the effectiveness of the proposed method.

Abstract Background Oral squamous cell carcinoma (OSCC) causes significant mortality and morbidity worldwide. Surgical resection with adjuvant radiotherapy remains the standard treatment for locally advanced resectable OSCC. Results from landmark trials have established postoperative concurrent cisplatin-radiotherapy (Cis-RT) as the standard treatment for OSCC patients with high-risk pathologic features. However, cisplatin-related toxicity limits usage in clinical practice. Given the need for effective but less toxic alternatives, we previously conducted a single-arm trial showing favorable safety profiles and promising efficacy of concurrent docetaxel-radiotherapy (Doc-RT). Methods In this randomized phase 2 trial, we aimed to compare Doc-RT with the standard Cis-RT in postoperative OSCC patients. Eligible patients had AJCC stage III–IV resectable OSCC with high-risk pathologic features. Two hundred twenty-four patients were enrolled and randomly assigned to receive concurrent Doc-RT or Cis-RT. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival (OS), locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), and adverse events (AEs). Integrin β1 (ITGB1) expression was analyzed as a biomarker for efficacy. Results After a median 28.8-month follow-up, 2-year DFS rates were 63.7% for Doc-RT arm and 56.1% for Cis-RT arm (p = 0.55). Meanwhile, Doc-RT demonstrated comparable efficacy to Cis-RT in OS, LRFS, and DMFS. Doc-RT resulted in fewer grade 3 or 4 hematological AEs. Low ITGB1 was associated with improved Doc-RT efficacy versus Cis-RT. Conclusions This randomized trial directly compared Doc-RT with Cis-RT for high-risk postoperative OSCC patients, with comparable efficacy and less toxicity. ITGB1 merits further validation as a predictive biomarker to identify OSCC patients most likely to benefit from Doc-RT. Findings indicate docetaxel may be considered as a concurrent chemoradiation option in this setting. Trial registration www.ClinicalTrials.gov . NCT02923258 (date of registration: October 4, 2016)

Abstract The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

Abstract Objective This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS). Methods Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (

Abstract Background Multiple high doses of 131I therapy in patients with differentiated thyroid cancer (DTC) might disrupt the balance of gut microbiota and metabolites. This study aimed to investigate the alterations of intestinal bacteria and metabolism over two courses of 131I therapy, explore the interactions, and construct diagnostic models reflecting enteric microecology based on 131I therapy. Methods A total of 81 patients were recruited for the first 131I therapy (131I-1st), among whom 16 received a second course (131I-2nd) after half a year. Fecal samples were collected 1 day before (Pre-131I-1st/2nd) and 3 days after (Post-131I-1st/2nd) 131I therapy for microbiome (16S rRNA gene sequencing) and metabolomic (LC–MS/MS) analyses. Results A total of six microbial genera and 11 fecal metabolites enriched in three pathways were identified to show significant differences between Pre-131I-1st and other groups throughout the two courses of 131I treatment. In the Post-131I-1st group, the beneficial bacteria Bifidobacterium, Lachnoclostridium, uncultured_bacterium_f_Lachnospiraceae, and Lachnospiraceae_UCG004 were abundant and the radiation-sensitive pathways of linoleic acid (LA), arachidonic acid, and tryptophan metabolism were inhibited compared with the Pre-131I-1st group. Compared with the Pre-131I-1st group, the Pre-131I-2nd group exhibited a reduced diversity of flora and differentially expressed metabolites, with a low abundance of beneficial bacteria and dysregulated radiation-sensitive pathways. However, less significant differences in microbiota and metabolites were found between the Pre/Post-131I-2nd groups compared with those between the Pre/Post-131I-1st groups. A complex co-occurrence was observed between 6 genera and 11 metabolites, with Lachnoclostridium, Lachnospiraceae_UCG004, Escherichia-Shigella, and LA-related metabolites contributing the most. Furthermore, combined diagnostic models of charactered bacteria and metabolites answered well in the early, long-term, and dose-dependent responses for 131I therapy. Conclusions Different stages of 131I therapy exert various effects on gut microecology, which play an essential role in regulating radiotoxicity and predicting the therapeutic response.

IntroductionDisorders of acid-base balance in the rumen of dairy cows have a significant impact on their health and performance. However, the effect of transient differences in pH on susceptibility to subacute ruminal acidosis (SARA) and lipopolysaccharide (LPS) biosynthesis in dairy cows remains unclear.MethodsIn this study, milk, serum, and rumen fluid samples from 40 Holstein dairy cows (on d 56 postpartum) with different rumen pH (2–4 h after morning feeding) were explored to investigate the difference of susceptibility to SARA and the correlation between microbiome, LPS and inflammation. These cows were categorized into low pH (LPH, pH ≤ 6.0, n = 20) and high pH (HPH, pH ≥ 6.5, n = 20) groups.ResultsThe results showed that LPH group increased the concentrations of total volatile fatty acids, acetate, propionate, butyrate and valerate. However, milk yield and milk compositions were unaffected. Compared to the HPH group, the LPH group increased the concentrations of serum BHBA, NEFA, LPS, HIS, IL-2, IL-6, TNF-α, and MDA, and decreased the concentrations of serum IgA, IgM, IgG, SOD, T-AOC, and mTOR. In addition, the LPH group decreased the copies of Ruminococcus flavefaciens and increased the copies of Fibrobacter succinogenes. Microbial community analysis isupplendicated a significant difference in bacterial composition between the two groups. At the phylum level, Bacteroidota and Firmicutes were enriched in the LPH and HPH groups, respectively. At the genus level, the dominant bacteria in the LPH group were Prevotella. Additionally, the LPH group increased the proportions of Gram-negative phenotypes, potentially pathogenic phenotypes and LPS biosynthesis. The close correlation between two key enzymes for LPS synthesis LpxL and LpxM with rumen pH, inflammatory markers, and microorganisms indicates that low pH may increase the risk of inflammation by facilitating the lysis of Gram-negative bacteria and the release of penta-acylated LPS. Penta-acylated and hexa-acylated LPS may be mainly derived from Prevotella and Succinivibrionaceae_UCG-001, respectively.DiscussionOverall, these results support the notion that transient low pH could reflect the risk of cows suffering from SARA and associated inflammation and is strongly associated with penta-acylated LPS. Our findings provide new insights into ruminant health improvement and disease prevention strategies.

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22–1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis.

Rich microbial communities are associated with tree decay, and they markedly impact the degradation of tree species and material cycling within ecosystems. The native Populus euphratica forests along the lower Tarim River of China are mostly mature or over-mature, with many tree trunks exhibiting features of extensive cavity decay and slow regeneration. In this study, a growth cone was used to drill a wood core at varying degrees of decay, and 16S and internal transcribed spacer techniques were used to identify the microbial structure (fungi and bacteria) within the wood core. Changes in the trunk microbial community under varying decay conditions were also examined. For healthy, lightly decayed, and heavily decayed trunk, the dominant bacterial and fungal phyla were Firmicutes and Actinobacteria, Ascomycota, and Basidiomycota, respectively. As decay progressed, the alpha diversity index of the microbial community tended to decline. The maximum number of differential species was found in healthy trunks, where leaner discriminant analysis effect size (LEfSe) of fungi and bacteria revealed 1 and 15 different species, respectively. Species network analysis showed that interspecific linkages were more complex within bacterial communities than within fungal communities, with the complexity of fungal interspecific relationship increasing as decay progressed. The microbial communities of P. euphratica trunks differed significantly with the varying degrees of decay. Microbes such as Ralstonia may also play key roles in the decay process. In addition to providing a foundation for the sustainable management of desert riparian forests, investigating the mechanisms through which microbial communities influence the deterioration of P. euphratica trunks provides information about the general health of P. euphratica forests.

BackgroundBoth pre-or post-COVID-19, older adults residing in nursing homes are at significant risk for social isolation, which is negatively associated with cognitive ability. Currently, the elderly aged 80 years and older are the fastest-growing age group globally. The extent of social isolation within this group post-COVID-19 and its impact on cognitive abilities remain inadequately explored.ObjectiveThis research aimed to evaluate the prevalence of social isolation among the oldest old in Chinese nursing homes post-COVID-19 and to investigate the mediating and moderating roles of basic activities of daily living (BADL), depression, and subjective socioeconomic status in the relationship between social isolation and cognitive ability.MethodsThis cross-sectional study included 453 participants aged 80 years and older from 11 nursing homes in Ningbo, Zhejiang Province, China. Social isolation was assessed using the Lubben Social Network Scale-6 (LSNS-6), cognitive ability using the Mini-Mental State Examination (MMSE), BADL using the Barthel Index (BI), and depression using the Patient Health Questionnaire-9 items (PHQ-9). Mediation and moderation effects were statistically analyzed using SPSS 23.0 and PROCESS 3.5.ResultsThe mean age of the study sample was 87.1 ± 3.8 years, among whom 60.3% (n = 273) were female, and 56.1% experienced social isolation, with 41.1% and 63.1% being isolated from family and friends, respectively. Social isolation indirectly affected cognitive ability through BADL and depression, respectively, and through the chain mediation effect of BADL and depression. Subjective socioeconomic status moderated the relationships between social isolation and BADL and between social isolation and depression. However, no moderating effect of subjective socioeconomic status was found between social isolation and cognitive ability.ConclusionThis study deepens our understanding of the current state of social isolation and its mechanisms of action in the oldest old post-COVID-19 and provides a new basis for future public health policy development and related research.

Abstract Prefabricated construction, a sustainable construction method, has become the inevitable trend for the future development of the construction industry. The subsidy policies for prefabricated construction enterprises can influence their strategies to promote the development of prefabricated construction. The paper considers a two-echelon prefabricated construction supply chain consisting of a manufacturer and an assembler, aiming to investigate pricing and the assembly rate strategies and coordination under different subsidy objects. The findings demonstrate that subsidy policies can increase the assembly rate. When the government subsidizes the manufacturer, the wholesale price decreases with the subsidy rate, while subsidizing the assembler, the wholesale price does not change. The impacts of subsidy policies on the retail price depend on price sensitivity and the consumer preference for the prefabricated construction market. When the subsidy rates are equivalent, the profit of supply chain with subsidizing the assembler is greater than that with subsidizing the manufacturer. Finally, the paper proposes the revenue-cost sharing contract to coordinate prefabricated construction supply chain with government subsidies. A numerical study is carried out to verify conclusions, and illustrates that a certain range of subsidy affects positively prefabricated construction enterprises by adjusting the retail price and increasing the assembly rate.

Abstract Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Repair of large bone defects caused by severe trauma, non-union fractures, or tumor resection remains challenging because of limited regenerative ability. Typically, these defects heal through mixed routines, including intramembranous ossification (IMO) and endochondral ossification (ECO), with ECO considered more efficient. Current strategies to promote large bone healing via ECO are unstable and require high-dose growth factors or complex cell therapy that cause side effects and raise expense while providing only limited benefit. Herein, we report a bio-integrated scaffold capable of initiating an early hypoxia microenvironment with controllable release of low-dose recombinant bone morphogenetic protein-2 (rhBMP-2), aiming to induce ECO-dominated repair. Specifically, we apply a mesoporous structure to accelerate iron chelation, this promoting early chondrogenesis via deferoxamine (DFO)-induced hypoxia-inducible factor-1α (HIF-1α). Through the delicate segmentation of click-crosslinked PEGylated Poly (glycerol sebacate) (PEGS) layers, we achieve programmed release of low-dose rhBMP-2, which can facilitate cartilage-to-bone transformation while reducing side effect risks. We demonstrate this system can strengthen the ECO healing and convert mixed or mixed or IMO-guided routes to ECO-dominated approach in large-size models with clinical relevance. Collectively, these findings demonstrate a biomaterial-based strategy for driving ECO-dominated healing, paving a promising pave towards its clinical use in addressing large bone defects.

Abstract Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide increases IRS1 stability and enhances insulin sensitivity. Importantly, administration of ERα-derived peptide into obese mice significantly improves glucose homeostasis and serum lipid profiles. These findings pave the way for the therapeutic intervention of T2DM by targeting the ligand-independent effect of ERα and indicate that ERα-derived peptide is a potential insulin sensitizer for the treatment of T2DM.

Abstract Background Abnormal expression of protein tyrosine kinase 6 (PTK6) has been proven to be involved in the development of gynecological tumors. However, its immune-related carcinogenic mechanism in other tumors remains unclear. Objective The aim of this study was to identify PTK6 as a novel prognostic biomarker in pan-cancer, especially in lung adenocarcinoma (LUAD), which is correlated with immune infiltration, and to clarify its clinicopathological and prognostic significance. Methods The prognostic value and immune relevance of PTK6 were investigated by using bio-informatics in this study. PTK6 expression was validated in vitro experiments (lung cancer cell lines PC9, NCI-H1975, and HCC827; human normal lung epithelial cells BEAS-2B). Western blot (WB) revealed the PTK6 protein expression in lung cancer cell lines. PTK6 expression was inhibited by Tilfrinib. Colony formation and the Cell Counting Kit-8 (CCK-8) assay were used to detect cell proliferation. The wound healing and trans-well were performed to analyze the cell migration capacity. Then flow cytometry was conducted to evaluate the cell apoptosis. Eventually, the relationship between PTK6 and immune checkpoints was examined. WB was used to estimate the PD-L1 expression at different Tilfrinib doses. Results PTK6 was an independent predictive factor for LUAD and was substantially expressed in LUAD. Pathological stage was significantly correlated with increased PTK6 expression. In accordance with survival analysis, poor survival rate in LUAD was associated with a high expression level of PTK6. Functional enrichment of the cell cycle and TGF-β signaling pathway was demonstrated by KEGG and GSEA analysis. Moreover, PTK6 expression considerably associated with immune infiltration in LUAD, as determined by immune analysis. Thus, the result of vitro experiments indicated that cell proliferation and migration were inhibited by the elimination of PTK6. Additionally, PTK6 suppression induced cell apoptosis. Obviously, PD-L1 protein expression level up-regulated while PTK6 was suppressed. Conclusion PTK6 has predictive value for LUAD prognosis, and could up regulated PD-L1.

Abstract Magnetic resonance imaging (MRI) has diverse applications in physics, biology, and medicine. Uniform excitation of nuclei spins through circular-polarized transverse magnetic component of electromagnetic field is vital for obtaining unbiased tissue contrasts. However, achieving this in the electrically large human body poses a significant challenge, especially at ultra-high fields (UHF) with increased working frequencies (≥297 MHz). Canonical volume resonators struggle to meet this challenge, while radiative excitation methods like travelling-wave (TW) show promise but often suffer from inadequate excitation efficiency. Here, we introduce a new technique using a subwavelength dielectric waveguide insert that enhances both efficiency and homogeneity at 7 T. Through TE11-to-TM11 mode conversion, power focusing, wave impedance matching, and phase velocity matching, we achieved a 114% improvement in TW efficiency and mitigated the center-brightening effect. This fundamental advancement in TW MRI through effective wave manipulation could promote the electromagnetic design of UHF MRI systems.

This study presents a novel refractive index sensor based on Fano resonance, incorporating a metal-insulator-metal (MIM) waveguide coupled with a circular ring structure (CRC). Using finite element method analysis, we investigated the propagation properties of the sensor. To evaluate their influence on sensor performance, we systematically varied the parameters of each Circular Resonant Cavity structure component, including the refractive index, employing a controlled variable approach. At its optimal configuration, the sensor achieves a maximum sensitivity of 3,240 nm/RIU and a figure of merit (FOM) of 57.9. With its high sensitivity, straightforward design, and suitability for temperature detection, the refractive index sensor holds promise for diverse applications.

BackgroundEffective management of diabetes mellitus (DM) involves comprehensive knowledge, attitudes, and practices (KAP) by nurses, which is essential for optimal patient care and aiding patients in their self-management of the condition.MethodThis survey evaluates nurses' self-assessed knowledge, attitudes, and practices (KAP) related to diabetes management, focusing on their perceptions of personnel expertise and care approaches. Using a stratified sampling method, the survey was disseminated across various online platforms from January 2023 to February 2024 within China, including WeChat and Sina Weibo. We employed binary logistic regression and Chi-square tests to explore the statistical correlates of KAP related to DM.ResultsA total of 4,011 nurses participated, revealing significant perceived knowledge deficiencies in specialized DM management areas, with only 34% (n = 1,360) proficient in current pharmacological treatments. Attitudinal assessments showed that 54% (n = 2,155) recognized the importance of cultural competence in dietary counseling. Practices were strong in routine glucose monitoring (96%, n = 3,851) but weaker in psychological support (68%, n = 2,736). Regression analysis indicated significant effects of experience on KAP, where nurses with 1–5 years of experience were more likely to show better knowledge (OR = 1.09; p = 0.08), and those with advanced degrees demonstrated higher competence (OR = 1.52; p = 0.028). Marital status influenced attitudes, with single nurses more likely to exhibit positive attitudes (OR = 0.49; p < 0.001), and work environment impacted knowledge, with hospital-based nurses more knowledgeable (OR = 1.15; p = 0.14). Additionally, gender differences emerged, with male nurses showing greater knowledge (OR = 1.65; p = 0.03) and better practices in diabetes care (OR = 1.47; p = 0.04).ConclusionThe study underscores the critical need for targeted educational programs and policy interventions to enhance nursing competencies in DM management. While the study provides valuable insights into nurses' perceptions of their competencies, future research should incorporate objective knowledge assessments to ensure a comprehensive understanding of their actual capabilities. Interestingly, the data also suggests a substantial opportunity to leverage technology and inter-professional collaboration to further enhance DM management efficacy among nurses, fostering an integrated care approach.

PurposeThe study aimed to investigate the correlation between the change of sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty(ICPP).MethodsEighteen girls with ICPP and 18 age-matched normal girls participated in this study, all of the participants had undergone physical measurements, laboratory tests, imaging examination and ocular surface assessments.ResultsThe Objective Scatter Index (OSI) in the ICPP group was significantly higher than in the control group (P = 0.031), girls with ICPP showed slightly lower MNITBUT compared to the normal control group, although this difference was not statistically significant. Bivariate analysis revealed a positive association between estradiol and OSI (r=0.383, P=0.021), Additionally, in the study population, both Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were negatively correlated with Mean noninvasive tear breakup time (MNITBUT) (r=-0.359, P=0.031)(r=-0.357, P=0.032).ConclusionIn comparison with the normal control group, alterations in the OSI were observed in girls with ICPP. This alteration may be associated with an elevation in estrogen levels. Although there was a slight non-significant decrease in NITBUT in ICPP girls, the negative correlation between LH and FSH with MNITBUT suggests new perspective for further investigation.

Abstract It is necessary to figure out the abnormal energy metabolites at the cellular level of postmenopausal osteoporosis (PMOP) bone microenvironment. In this study, we constructed PMOP model by ovariectomy and identified 9 differential metabolites compared with control femur by energy metabolomic. The enrichment analysis of differential metabolites revealed that tricarboxylic acid cycle, glucagon pathway and purinergic signaling pathway were the main abnormal metabolic processes. Citric acid was identified as the key metabolite by constructing compound reaction–enzyme–gene network. The functional annotation of citric acid targets identified by network pharmacological tools indicated that matrix metalloproteinase 9 (MMP-9) may be involved in regulating citric acid metabolism in the osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC). Molecular docking shows that the interaction forces between MMP-9 and citric acid synthase (CS) is −638, and there are multiple groups of residues used to form hydrogen bonds. Exogenous H2O2 promotes the expression of MMP-9 in BMSC to further degrade CS resulting in a decrease in mitochondrial citric acid synthesis, which leads to the disorder of bone remodeling by two underlying mechanisms ((1) the decreased histone acetylation inhibits the osteogenic differentiation potential of BMSC; (2) the decreased bone mineralization by citric acid deposition). MMP-9-specific inhibitor (MMP-9-IN-1) could significantly improve the amount of CS in BMSC to promote cellular citric acid synthesis, and further enhance bone remodeling. These findings suggest inhibiting the degradation of CS by MMP-9 to promote the net production of citric acid in osteogenic differentiation of BMSC may be a new direction of PMOP research.

Background & Aims: The O-class of the forkhead transcription factor FoxO1 is a crucial factor mediating insulin→PI3K→Akt signaling and governs diverse cellular processes. However, the role of hepatocyte FoxO1 in liver fibrosis has not been well-established. In his study, we investigated the role of hepatocyte FoxO1 in liver fibrosis and uncovered the underlying mechanisms. Methods: Liver fibrosis was established by carbon tetrachloride (CCL4) administration and compared between liver-specific deletion of FoxO1 deletion (F1KO) and control (CNTR) mice. Using genetic and bioinformatic strategies in vitro and in vivo, the role of hepatic FoxO1 in liver fibrosis and associated mechanisms was established. Results: Increased FoxO1 expression and FoxO1 signaling activation were observed in CCL4-induced fibrosis. Hepatic FoxO1 deletion largely attenuated CCL4-induced liver injury and fibrosis compared with CNTR mice. F1KO mice showed ameliorated CCL4-induced hepatic inflammation and decreased TGF-β1 mRNA and protein levels compared with those of CNTR mice. In primary hepatocytes, FoxO1 deficiency reduced TGF-β1 expression and secretion. Conditioned medium (CM) collected from wild-type hepatocytes treated with CCL4 activated human HSC cell line (LX-2); such effect was attenuated by FoxO1 deletion in primary hepatocytes or neutralization of TGF-β1 in the CM using TGF-β1 antibody. Hepatic FoxO1 overexpression in CNTR mice promoted CCL4-induced HSC activation; such effect was blocked in L-TGF-β1KO mice. Conclusions: Hepatic FoxO1 mediates CCL4-inducled liver fibrosis via upregulating hepatocyte TGF-β1 expression, stimulating hepatic inflammation and TGF-β1-mediated HSC activation. Hepatic FoxO1 may be a therapeutic target for prevention and treatment of liver fibrosis.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor–bed ratio and nurse–bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

Illegal electricity users pose a significant threat to the economic and security aspects of the power system by illicitly accessing or manipulating electrical resources. With the widespread adoption of Advanced Metering Infrastructure (AMI), researchers have turned to leveraging smart meter data for electricity theft detection. However, existing models rely on methods that model a single electricity load curve and cannot capture the temporal dependencies, periodicity, and underlying features between electricity consumption cycles. This study introduces a novel electricity theft detection method based on dynamic residual graph networks. Innovatively, it proposes a dynamic topological graph construction technique that allows for the real-time updating of adjacency matrices during the training process, thereby effectively capturing the complex relationships in electricity usage patterns. Utilizing the MixHop graph convolutional network, it delves into the temporal sequence dependencies, periodicity, and hidden characteristics within user electricity consumption data. Additionally, to address the issue of model instability caused by scarce theft data, we employ the SMOTE (Synthetic Minority Over-sampling Technique) oversampling technique and enhance overall classification performance by modifying class weights in the loss function. We trained this network architecture on the real SGCC (State Grid Corporation of China) dataset, and the results demonstrate its superiority over other mainstream existing models.

In this paper, a novel ultrawideband phased array is presented based on exponential curve modified dipoles. A tightly-coupled exponential curve modified dipole arm is used to extend the operating bandwidth with a simple coplanar strip structure, which avoids the use of additional complex impedance conversion networks and reduces the processing difficulty and cost. The problematic common-mode resonance is moved out of the required operating bandwidth by the shorting pin. A wide angle impedance matching layer is used to improve beam scanning ability of the array. The proposed antenna array achieves 8.5:1 (2.06-17.6 GHz) bandwidth at broadside, with a scanning range of ±45° from 2.06-17.6 GHz (8.5:1 bandwidth) in the E-plane and ±45° from 2.2-17.6 GHz (8:1 bandwidth) in the H-plane, subject to active VSWR < 3. A $6\times6$ prototype was fabricated and measured with good agreement in measured and simulated results, which verify the ultrawideband performance of proposed array.

Remote sensing image object detection with deep neural networks has been highly successful, but it heavily relies on a large number of labeled samples for optimal performance. Unfortunately, when faced with limited labeled samples, the performance of object detection deteriorates. In order to overcome these limitations, we propose a few-shot object detection (FSOD) method based on the reweighting of contrastive class-attention features for remote sensing images. A Siamese representation embedding model based on contrastive learning with a distinguishing operator is proposed to deal with interclass feature ambiguity between base classes and novel classes under complex backgrounds. At the same time, the attention class weights method on region of interest (ROI) features is utilized to boost the discrimination of the novel class features. We conducted comprehensive experiments on two widely used remote sensing object detection datasets, RSOD and DIOR. The proposed FSOD model demonstrated superior performance compared to MM-RCNN, achieving an improvement of approximately 4.7% in terms of mAP on the DIOR dataset. In addition, in comparison to the self-adaptive attention network (SAAN), the FSOD model exhibited an improvement of approximately 3.4% in mAP on the RSOD dataset.

[INLINE:1] Vascular etiology is the second most prevalent cause of cognitive impairment globally. Endothelin-1, which is produced and secreted by endothelial cells and astrocytes, is implicated in the pathogenesis of stroke. However, the way in which changes in astrocytic endothelin-1 lead to poststroke cognitive deficits following transient middle cerebral artery occlusion is not well understood. Here, using mice in which astrocytic endothelin-1 was overexpressed, we found that the selective overexpression of endothelin-1 by astrocytic cells led to ischemic stroke-related dementia (1 hour of ischemia; 7 days, 28 days, or 3 months of reperfusion). We also revealed that astrocytic endothelin-1 overexpression contributed to the role of neural stem cell proliferation but impaired neurogenesis in the dentate gyrus of the hippocampus after middle cerebral artery occlusion. Comprehensive proteome profiles and western blot analysis confirmed that levels of glial fibrillary acidic protein and peroxiredoxin 6, which were differentially expressed in the brain, were significantly increased in mice with astrocytic endothelin-1 overexpression in comparison with wild-type mice 28 days after ischemic stroke. Moreover, the levels of the enriched differentially expressed proteins were closely related to lipid metabolism, as indicated by Kyoto Encyclopedia of Genes and Genomes pathway analysis. Liquid chromatography-mass spectrometry nontargeted metabolite profiling of brain tissues showed that astrocytic endothelin-1 overexpression altered lipid metabolism products such as glycerol phosphatidylcholine, sphingomyelin, and phosphatidic acid. Overall, this study demonstrates that astrocytic endothelin-1 overexpression can impair hippocampal neurogenesis and that it is correlated with lipid metabolism in poststroke cognitive dysfunction.

At present, a large number of rumors are mixed in with various kinds of news, such as current affairs, politics, social economy, and military activities, which seriously reduces the credibility of Internet information and hinders the positive development of various fields. In previous research on rumors, most scholars have focused their attention on the textual features, contextual semantic features, or single-emotion features of rumors but have not paid attention to the chain reaction caused by the hidden emotions in comments in social groups. Therefore, this paper comprehensively uses the emotional signals in rumor texts and comments to extract emotional features and determines the relationship between them to establish dual-emotion features. The main research achievements include the following aspects: (1) this study verifies that, in the field of affective characteristics, the combination of rumor-text emotion and comment emotion is superior to other baseline affective characteristics, and the detection performance of each component is outstanding; (2) the results prove that the combination of dual-emotion features and a semantic-feature-based detector (BiGRU and CNN) can improve the effectiveness of the detector; (3) this paper proposes reconstructing the dataset according to time series to verify the generalization ability of dual affective features; (4) the attention mechanism is used to combine domain features and semantic features to extract more fine-grained features. A large number of data experiments show that the dual-emotion features can be effectively compatible with an existing rumor detector, enhance the detector’s performance, and improve the detection accuracy.

Bovine respiratory syncytial virus (BRSV) is an RNA virus with envelope that causes acute, febrile, and highly infectious respiratory diseases in cattle. However, the manner and mechanism of BRSV entry into cells remain unclear. In this study, we aimed to explore the entry manner of BRSV into MDBK cells and its regulatory mechanism. Our findings, based on virus titer, virus copies, western blot and IFA analysis, indicate that BRSV enters MDBK cells through endocytosis, relying on dynamin, specifically via clathrin-mediated endocytosis rather than caveolin-mediated endocytosis and micropinocytosis. We observed that the entered BRSV initially localizes in early endosomes and subsequently localizes in late endosomes. Additionally, our results of western blot, virus titer and virus copies demonstrate that BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways. Overall, our study suggests that BRSV enters MDBK cells through clathrin-mediated endocytosis, entered BRSV is trafficked to late endosome via early endosome, BRSV entry through clathrin-mediated endocytosis is regulated by PI3K-Akt and Src-JNK signaling pathways.

Objective To investigate the effects of hydrogen therapy on epileptic seizures in rats with refractory status epilepticus and the underlying mechanisms. Methods Status epilepticus was induced using pilocarpine. The effects of hydrogen treatment on epilepsy severity in model rats were then monitored using Racine scores and electroencephalography (EEG), followed by western blot of plasma membrane N-methyl-D-aspartate receptor subtype 2B (NR2B) and phosphorylated NR2B expression. We also generated a cellular epilepsy model using Mg 2+ -free medium and used polymerase chain reaction to investigate the neuroprotective effects of hydrogen. Results There were no significant differences in Racine scores between the hydrogen and control groups. EEG amplitudes were lower in the hydrogen treatment group than in the control group. In epilepsy model rats, hippocampal cell membrane NR2B expression and phosphorylation increased gradually over time. Although hippocampal cell membrane NR2B expression was not significantly different between the two groups, NR2B phosphorylation levels were significantly lower in the hydrogen group. Hydrogen treatment also increased superoxide dismutase, mitochondrial (SOD2) expression. Conclusions Hydrogen treatment reduced EEG amplitudes and NR2B phosphorylation; it also decreased neuronal death by reducing oxidative stress. Hydrogen may thus be a potential treatment for refractory status epilepticus by inhibiting membrane NR2B phosphorylation and oxidative stress.

Abstract Background Retained placenta is a concern during labor and delivery. However, recent data regarding the profiles of retained placenta are scarce, especially nationwide and in minority populations. This study aimed to investigate the recent incidence of retained placenta and its associated outcomes. Methods We retrospectively analyzed an American population-based data from the National Inpatient Sample (NIS) 2016–2019. The outcomes of interest included the incidence of retained placenta, in-hospital mortality, length of hospital stay, and hospitalization costs. We estimated the incidence for retained placenta overall and by racial and ethnic subgroups, utilizing survey weights standardized for each subgroup. Multivariable linear or logistic regression models were employed in our study to investigate the associations between retained placenta and the impact of in-hospital mortality, duration of stay, and hospitalization expenditures for the entire population and further stratified by race and ethnicity, adjusting for potential confounders. Results Of the 13,848,131 deliveries, there were 108,035 (or 0.78%) birthing persons were identified as having retained placentas. Over time, the incidence of retained placenta increased from 730 per 100,000 (0.73%) in 2016 to 856 per 100,000 (0.86%) in 2019. Native American mothers have the highest rate of retained placenta, with a prevalence almost twice that of the general population, reaching 1,434 cases per 100,000 (1.43%). After adjusting for confounding factors, Native American mothers were more likely to have retained placenta (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.35–1.81), whereas Black (OR, 0.92; 95% CI, 0.88–0.97) and Hispanic mothers (OR, 0.84; 95% CI, 0.80–0.89) were significantly less likely to have retained placenta than White mothers. Furthermore, those who delivered with a retained placenta were significantly associated with higher in-hospital mortality, a longer duration of stay, and hospitalization expenditures, which were disproportionately varied by maternal race and ethnicity. Conclusions The incidence of retained placenta among people undergoing vaginal delivery is exhibiting an upward trend over time, with notable variations observed across different ethnic groups by unclear mechanisms. The ramifications of these findings have the potential to impact the clinical management of maternal health care and the creation of health policies, specifically in relation to the Native American birth population.

Aims: Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis. Methods: The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene. Results: Melatonin promoted apoptosis of RAW264.7 cells and increased the expression of BMAL1 to inhibit the activation of ROS and phosphorylation of mitogen-activated protein kinase (MAPK)-p38. Silencing the bmal1 gene weakened the above effects of melatonin. After that, we used dehydrocorydaline (DHC) to enhance the activation of MAPK-p38, and the effects of melatonin on reducing ROS levels and promoting apoptosis of RAW264.7 cells were also blocked. Then, we constructed a mouse model of postmenopausal osteoporosis and administered melatonin. The results showed that melatonin improves bone loss in ovariectomized mice. Finally, we established a model of overexpression of the bmal1 gene, and these results suggest that the bmal1 gene can regulate ROS activity and change the level of the MAPK-p38 signalling pathway. Conclusion: Our study confirmed that melatonin promotes the apoptosis of RAW264.7 cells through BMAL1/ROS/MAPK-p38, and revealed the therapeutic effect and mechanism of melatonin in postmenopausal osteoporosis. This finding enriches BMAL1 as a potential target for the treatment of osteoporosis and the pathogenesis of postmenopausal osteoporosis. Cite this article: Bone Joint Res 2023;12(11):677–690.

Abstract Pancreatic ductal adenocarcinoma (PDAC) tumours carry multiple gene mutations and respond poorly to treatments. There is currently an unmet need for drug carriers that can deliver multiple gene cargoes to target high solid tumour burden like PDAC. Here, we report a dual targeted extracellular vesicle (dtEV) carrying high loads of therapeutic RNA that effectively suppresses large PDAC tumours in mice. The EV surface contains a CD64 protein that has a tissue targeting peptide and a humanized monoclonal antibody. Cells sequentially transfected with plasmid DNAs encoding for the RNA and protein of interest by Transwell®-based asymmetric cell electroporation release abundant targeted EVs with high RNA loading. Together with a low dose chemotherapy drug, Gemcitabine, dtEVs suppress large orthotopic PANC-1 and patient derived xenograft tumours and metastasis in mice and extended animal survival. Our work presents a clinically accessible and scalable way to produce abundant EVs for delivering multiple gene cargoes to large solid tumours.

Abstract The recent success of mRNA therapeutics against pathogenic infections has increased interest in their use for other human diseases including cancer. However, the precise delivery of the genetic cargo to cells and tissues of interest remains challenging. Here, we show an adaptive strategy that enables the docking of different targeting ligands onto the surface of mRNA-loaded small extracellular vesicles (sEVs). This is achieved by using a microfluidic electroporation approach in which a combination of nano- and milli-second pulses produces large amounts of IFN-γ mRNA-loaded sEVs with CD64 overexpressed on their surface. The CD64 molecule serves as an adaptor to dock targeting ligands, such as anti-CD71 and anti-programmed cell death-ligand 1 (PD-L1) antibodies. The resulting immunogenic sEVs (imsEV) preferentially target glioblastoma cells and generate potent antitumour activities in vivo, including against tumours intrinsically resistant to immunotherapy. Together, these results provide an adaptive approach to engineering mRNA-loaded sEVs with targeting functionality and pave the way for their adoption in cancer immunotherapy applications.

Abstract Background The WHO grade and Ki-67 index are independent indices used to evaluate the malignant biological behavior of meningioma. This study aims to develop MRI-based machine learning models to predict the malignant biological behavior of meningioma from the perspective of the WHO grade, Ki-67 index, and their combination. Methods This multicenter, retrospective study included 313 meningioma patients, of which 70 were classified as high-grade (WHO II/III) and 243 as low-grade (WHO I). The Ki-67 expression was classified into low-expression (n = 216) and high-expression (n = 97) groups with a threshold of 5%. Among them, there were 128 patients with malignant biological behavior whose WHO grade or Ki-67 index increased either or both. Data from Center A and B are were utilized for model development, while data from Center C and D were used for external validation. Radiomic features were extracted from the maximum cross-sectional area (2D) region of Interest (ROI) and the whole tumor volume (3D) ROI using different paraments from the T1, T2-weighted, and T1 contrast-enhanced sequences (T1CE), followed by five independent feature selections and eight classifiers. 240 prediction models were constructed to predict the WHO grade, Ki-67 index and their combination respectively. Models were evaluated by cross-validation in training set (n = 224). Suitable models were chosen by comparing the cross-validation (CV) area under the curves (AUC) and their relative standard deviations (RSD). Clinical and radiological features were collected and analyzed; meaningful features were combined with radiomic features to establish the clinical-radiological-radiomic (CRR) models. The receiver operating characteristic (ROC) analysis was used to evaluate those models in validation set. Radiomic models and CRR models were compared by Delong test. Results 1218 and 1781 radiomic features were extracted from 2D ROI and 3D ROI of each sequence. The selected grade, Ki-67 index and their combination radiomic models were T1CE-2D-LASSO-LR, T1CE-3D-LASSO-NB, and T1CE-2D-LASSO-LR, with cross-validated AUCs on the training set were 0.857, 0.798, and 0.888, the RSDs were 0.06, 0.09, and 0.05, the validation set AUCs were 0.829, 0.752, and 0.904, respectively. Heterogeneous enhancement was found to be associated with high grade and Ki-67 status, while surrounding invasion was associated with the high grade status, peritumoral edema and cerebrospinal fluid space surrounding tumor were correlated with the high Ki-67 status. The Delong test showed that these significant radiological features did not significantly improve the predictive performance. The AUCs for CRR models predicting grade, Ki-67 index, and their combination in the validation set were 0.821, 0.753, and 0.906, respectively. Conclusions This study demonstrated that MRI-based machine learning models could effectively predict the grade, Ki-67 index of meningioma. Models considering these two indices might be valuable for improving the predictive sensitivity and comprehensiveness of prediction of malignant biological behavior of meningioma.

Abstract Despite impressive progress in face super‐resolution (SR), it is an open challenge to reconstruct a reliable SR face that preserves authentic facial characteristics. Here, the problem of super‐resolving low‐resolution (LR) faces to high‐resolution (HR) ones is addressed. To tackle the ill‐posed nature of face SR, the cascaded super‐resolution network (CSRNet) is proposed to utilize shape and identity priors jointly and progressively, the first to explore multiple priors. Specifically, CSRNet adopts a cascaded structure to transform an LR face to HR face progressively via multiple stages. At each stage, CSRNet forces its output face image to match both the shape priors and identity priors extracted from the ground‐truth HR face. The shape priors estimated in one stage are merged into the inputs of its subsequent stage to provide rich information for the face SR. To generate realistic yet discriminative faces, the cascaded super‐resolution generative adversarial network (CSRGAN) is also proposed to incorporate the adversarial loss and identification loss into CSRNet. Extensive experiments on popular benchmarks show that the CSRNet and CSRGAN outperform existing face SR state‐of‐the‐art methods, both quantitatively and qualitatively, and detailed ablation studies show the advantage of this method.

Small UAV target detection and tracking based on cross-modality image fusion have gained widespread attention. Due to the limited feature information available from small UAVs in images, where they occupy a minimal number of pixels, the precision required for detection and tracking algorithms is particularly high in complex backgrounds. Image fusion techniques can enrich the detailed information for small UAVs, showing significant advantages under extreme lighting conditions. Image registration is a fundamental step preceding image fusion. It is essential to achieve accurate image alignment before proceeding with image fusion to prevent severe ghosting and artifacts. This paper specifically focused on the alignment of small UAV targets within infrared and visible light imagery. To address this issue, this paper proposed a cross-modality image registration network based on deep learning, which includes a structure preservation and style transformation network (SPSTN) and a multi-level cross-attention residual registration network (MCARN). Firstly, the SPSTN is employed for modality transformation, transferring the cross-modality task into a single-modality task to reduce the information discrepancy between modalities. Then, the MCARN is utilized for single-modality image registration, capable of deeply extracting and fusing features from pseudo infrared and visible images to achieve efficient registration. To validate the effectiveness of the proposed method, comprehensive experimental evaluations were conducted on the Anti-UAV dataset. The extensive evaluation results validate the superiority and universality of the cross-modality image registration framework proposed in this paper, which plays a crucial role in subsequent image fusion tasks for more effective target detection.

This paper introduces a novel plasmon refractive index nanosensor structure based on Fano resonance. The structure comprises a metal–insulator–metal (MIM) waveguide with an inverted rectangular cavity and a circle minus a small internal circle plus a rectangular cavity (CMSICPRC). This study employs the finite element method (FEM) to analyze the sensing characteristics of the structure. The results demonstrate that the geometrical parameters of specific structures exert a considerable influence on the sensing characteristics. Simulated experimental data show that the maximum sensitivity of this structure is 3240 nm/RIU, with a figure of merit (FOM) of 52.25. Additionally, the sensor can be used in biology, for example, to detect the concentration of hemoglobin in blood. The sensitivity of the sensor in this application, according to our calculations, can be 0.82 nm∙g/L.

The recent worldwide incidence of mpox infection and concerns about future emerging variants of mpox viruses highlight the need for the development of a new generation of mpox vaccines. To achieve this goal, we utilized our norovirus S nanoparticle vaccine platform to produce and evaluate two pseudovirus nanoparticles (PVNPs), S-L1 and S-J1. These PVNPs displayed the L1 neutralizing antigen target of the vaccinia virus and a yet-untested J1 antigen of the mpox virus, respectively, with the aim of creating an effective nanoparticle-based mpox vaccine. Each self-assembled PVNP consists of an inner shell resembling the interior layer of the norovirus capsid and multiple L1 or J1 antigens on the surface. The PVNPs improved the antibody responses toward the displayed L1 or J1 antigens in mice, resulting in significantly greater L1/J1-specific IgG and IgA titers than those elicited by the corresponding free L1 or J1 antigens. After immunization with the S-L1 PVNPs, the mouse sera exhibited high neutralizing antibody titers against the vaccinia virus, and the S-L1 PVNPs provided mice with 100% protection against mortality caused by vaccinia virus challenge. In contrast, the S-J1 PVNPs induced low neutralizing antibody titers and conferred mice weak protective immunity. These data confirm that the L1 protein is an excellent vaccine target and that the readily available S-L1 PVNPs are a promising mpox vaccine candidate worthy of further development.

For modern radar systems, small unmanned aerial vehicles (UAVs) belong to a typical types of targets with ‘low, slow, and small’ characteristics. In complex combat environments, the functional requirements of radar systems are not only limited to achieving stable detection and tracking performance but also to effectively complete the recognition of small UAV targets. In this paper, a multi-dimensional feature fusion framework for small UAV target recognition utilizing a small-sized and low-cost high-resolution radar is proposed, which can fully extract and combine the geometric structure features and the micro-motion features of small UAV targets. For the performance analysis, the echo data of different small UAV targets was measured and collected with a millimeter-wave radar, and the dataset consists of high-resolution range profiles (HRRP) and micro-Doppler time–frequency spectrograms was constructed for training and testing. The effectiveness of the proposed method was demonstrated by a series of comparison experiments, and the overall accuracy of the proposed method can reach 98.5%, which demonstrates that the proposed multi-dimensional feature fusion method can achieve better recognition performance than that of classical algorithms and higher robustness than that of single features for small UAV targets.

Microglia, as resident macrophages in the central nervous system, play a multifunctional role in the pathogenesis of Alzheimer’s disease (AD). Their clustering around amyloid-β (Aβ) deposits is a core pathological feature of AD. Recent advances in single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) have revealed dynamic changes in microglial phenotypes over time and across different brain regions during aging and AD progression. As AD advances, microglia primarily exhibit impaired phagocytosis of Aβ and tau, along with the release of pro-inflammatory cytokines that damage synapses and neurons. Targeting microglia has emerged as a potential therapeutic approach for AD. Treatment strategies involving microglia can be broadly categorized into two aspects: (1) enhancing microglial function: This involves augmenting their phagocytic ability against Aβ and cellular debris and (2) mitigating neuroinflammation: Strategies include inhibiting TNF-α signaling to reduce the neuroinflammatory response triggered by microglia. Clinical trials exploring microglia-related approaches for AD treatment have garnered attention. Additionally, natural products show promise in enhancing beneficial effects and suppressing inflammatory responses. Clarifying microglial dynamics, understanding their roles, and exploring novel therapeutic approaches will advance our fight against AD.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease worldwide. Caspase 8 and FADD-like apoptosis regulator (CFLAR) has been identified as a potent factor in mitigating non-alcoholic steatohepatitis (NASH) by inhibiting the N-terminal dimerization of apoptosis signal-regulating kinase 1 (ASK1). While arginine methyltransferase 1 (PRMT1) was previously reported to be associated with increased hepatic glucose production, its involvement in hepatic lipid metabolism remains largely unexplored. The interaction between PRMT1 and CFLAR and the methylation of CFLAR were verified by Co-IP and immunoblotting assays. Recombinant adenoviruses were generated for overexpression or knockdown of PRMT1 in hepatocytes. The role of PRMT1 in NAFLD was investigated in normal and high-fat diet-induced obese mice. In this study, we found a significant upregulation of PRMT1 and downregulation of CFLAR after 48h of fasting, while the latter significantly rebounded after 12h of refeeding. The expression of PRMT1 increased in the livers of mice fed a methionine choline-deficient (MCD) diet and in hepatocytes challenged with oleic acid (OA)/palmitic acid (PA). Overexpression of PRMT1 not only inhibited the expression of genes involved in fatty acid oxidation (FAO) and promoted the expression of genes involved in fatty acid synthesis (FAS), resulting in increased triglyceride accumulation in primary hepatocytes, but also enhanced the gluconeogenesis of primary hepatocytes. Conversely, knockdown of hepatic PRMT1 significantly alleviated MCD diet-induced hepatic lipid metabolism abnormalities and liver injury in vivo, possibly through the upregulation of CFLAR protein levels. Knockdown of PRMT1 suppressed the expression of genes related to FAS and enhanced the expression of genes involved in FAO, causing decreased triglyceride accumulation in OA/PA-treated primary hepatocytes in vitro. Although short-term overexpression of PRMT1 had no significant effect on hepatic triglyceride levels under physiological conditions, it resulted in increased serum triglyceride and fasting blood glucose levels in normal C57BL/6J mice. More importantly, PRMT1 was observed to interact with and methylate CFLAR, ultimately leading to its ubiquitination-mediated protein degradation. This process subsequently triggered the activation of c-Jun N-terminal kinase 1 (JNK1) and lipid deposition in primary hepatocytes. Together, these results suggested that PRMT1-mediated methylation of CFLAR plays a critical role in hepatic lipid metabolism. Targeting PRMT1 for drug design may represent a promising strategy for the treatment of NAFLD.