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Abstract Background This study aimed to develop a new ultrasonographic dating formula to estimate gestational age (GA) based on fetal crown–rump length (CRL) in a Chinese population, evaluate model accuracy and compare its performance with established dating formulas. Methods A prospective, multicenter study was conducted across mainland China. Participants included healthy, low-risk women with spontaneously conceived singleton pregnancies and a regular menstrual cycle in the preceding year. Ultrasonography was performed between 11 and 14 weeks of gestation, with GA determined based on the last menstrual period. Participants were randomly assigned to a development or validation cohort in a 7:3 ratio. A best-fit regression model was constructed for GA estimation based on CRL in the development cohort. For validation, mean differences between the new estimated GA and menstrual age were calculated and compared with those obtained using five established CRL-based dating formulas in the validation cohort. All participants were followed through to delivery. Results The study recruited 4,710 women with singleton pregnancies, with 3,297 in the development cohort and 1,413 women in the validation cohort. The mean and standard deviation values of CRL changed linearly with GA during 11–14 weeks. CRL demonstrated a linear relationship with GA between 11 and 14 weeks, yielding the regression equation GA = 59.590085 + 0.458539×CRL (R2 = 0.8042). The mean difference between estimated GA and menstrual age was 0.32 days (95% confidence interval 0.17–0.46), demonstrating a smaller error compared with those obtained from the five widely used CRL dating formulas. Conclusions We derived a CRL-based dating formula applicable to naturally conceived pregnancies at 11–14 weeks. This new formula exhibits small residuals, providing a more accurate alternative to existing CRL-based dating formulas.

Abstract The effects of transarterial chemoembolization (TACE) on the systemic immune in hepatocellular carcinoma (HCC) are not well understood. We aimed to reveal the temporal and spatial changes in the immune profile of peripheral blood and tumor tissues in HCC patients following TACE. Eighty-four HCC patients were included, 20 of whom received TACE with a median follow-up of 28 months. Immune cell proportion within peripheral blood was profiled with flow cytometry, and therapeutic efficacy was evaluated by imaging examinations. Additionally, cell distribution within tumor microenvironment (TME) were compared between the necrotic tumor infiltration zone (N-IZ) and the residual tumor infiltration zone (R-IZ) by multiplex immunofluorescence. Among 20 patients, 25% (5/20) achieved complete response, and 75% (15/20) showed partial response. Fourteen patients received combinational targeted therapy and immunotherapy and the median progression-free survival was 15.5 months. Compared to healthy individuals, HCC exhibited significantly higher proportions of regulatory T cells (Tregs) and programmed death-1 receptor (PD1)+ Tregs within peripheral blood. PD1+ Treg cells, PD1+ CD4+ T cells and PD1+ CD8+ T cells decreased significantly within peripheral blood after TACE. In TME, N-IZ showed significantly lower CD4+ T, CD8+ T and FOXP3+ Tregs, higher PD1+ CD8+/CD8+ and PD1+ CD8+/ PD1+ FOXP3+. Moreover, the spatial distance between CD8+ T cells and the nearest FOXP3+ Tregs in N-IZ was significantly greater than in R-IZ. Our findings demonstrated that TACE could both remodel the immune components in peripheral blood and TME, strengthening the rationale for developing immunotherapy alongside TACE.

Abstract Background Collagen type X (ColXα1, encoded by COL10A1) is expressed specifically in the cartilage-to-bone transition, in bone marrow cells, and in osteoarthritic (OA) cartilage. We have previously shown that ColXα1 is expressed in breast tumor stroma, correlates with tumor-infiltrating lymphocytes, and predicts poor adjuvant therapy outcomes in ER+/HER2+ breast cancer. However, the underlying molecular mechanisms for these effects are unknown. In this study, we performed bioinformatic analysis of COL10A1-associated gene modules in breast and pancreatic cancer as well as in cells from bone marrow and OA cartilage. These findings provide important insights into the mechanisms of transcriptional and extracellular matrix changes which impact the local stromal microenvironment and tumor progression. Methods Immunohistochemistry was performed to examine collagen type X expression in solid tumors. WGCNA was used to generate COL10A1-associated gene networks in breast and pancreatic tumor cohorts using RNA-Seq data from The Cancer Genome Atlas. Computational analysis was employed to assess the impact of these gene networks on development and progression of cancer and OA. Data processing and statistical analysis was performed using R and various publicly-available computational tools. Results Expression of COL10A1 and its associated gene networks highlights inflammatory and immunosuppressive microenvironments, which identify aggressive breast and pancreatic tumors and contribute to metastatic potential in a sex-dependent manner. Both cancer types are enriched in stroma, and COL10A1 implicates bone marrow-derived fibroblasts as contributors to the epithelial-to-mesenchymal transition (EMT) in these tumors. Heightened expression of COL10A1 and its associated gene networks is correlated with poorer patient outcomes in both breast and pancreatic cancer. Common transcriptional changes and chondrogenic activity are shared between cancer and OA cartilage, suggesting that similar microenvironmental alterations may underlie both diseases. Conclusions COL10A1-associated gene networks may hold substantial value as regulators and biomarkers of aggressive tumor phenotypes with implications for therapy development and clinical outcomes. Identification of tumors which exhibit high expression of COL10A1 and its associated genes may reveal the presence of bone marrow-derived stromal microenvironments with heightened EMT capacity and metastatic potential. Our analysis may enable more effective risk assessment and more precise treatment of patients with breast and pancreatic cancer.

Abstract Recent studies have highlighted the potential association between common benign epilepsy syndromes in children and the development of partial cognitive impairment. We established a comprehensive database of cognitive, structural magnetic resonance imaging (sMRI), and resting-state functional magnetic resonance imaging (rsfMRI) data obtained from a cohort of 36 Chinese paediatric volunteers. The participants, aged 5–16 years, were specifically diagnosed with either benign epilepsy with centrotemporal spikes (BECTs) or childhood absence epilepsy by certified paediatric neurologists. All imaging data were collected by qualified clinicians, and cognitive data were collected within 1 year of magnetic resonance imaging data collection. This database allows researchers to perform more detailed analyses using multimodal data to explore the relationship between cognitive impairment and brain mechanisms in children with common epilepsy syndromes.

Abstract To reveal the fundamental aspects hidden behind a variety of transient events in mechanics, physics, and biology, the highly desired ability to acquire three-dimensional (3D) images with ultrafast temporal resolution has been long sought. As one of the most commonly employed 3D sensing techniques, fringe projection profilometry (FPP) reconstructs the depth of a scene from stereo images taken with sequentially structured illuminations. However, the imaging speed of current FPP methods is generally capped at several kHz, which is limited by the projector-camera hardware and the number of fringe patterns required for phase retrieval and unwrapping. Here we report a novel learning-based ultrafast 3D imaging technique, termed single-shot super-resolved FPP (SSSR-FPP), which enables ultrafast 3D imaging at 100,000 Hz. SSSR-FPP uses only one pair of low signal-to-noise ratio (SNR), low-resolution, and pixelated fringe patterns as input, while the high-resolution unwrapped phase and fringe orders can be deciphered with a specific trained deep neural network. Our approach exploits the significant speed gain achieved by reducing the imaging window of conventional high-speed cameras, while “regenerating” the lost spatial resolution through deep learning. To demonstrate the high spatio-temporal resolution of SSSR-FPP, we present 3D videography of several transient scenes, including rotating turbofan blades, exploding building blocks, and the reciprocating motion of a steam engine, etc., which were previously challenging or even impossible to capture with conventional methods. Experimental results establish SSSR-FPP as a significant step forward in the field of 3D optical sensing, offering new insights into a broad spectrum of dynamic processes across various scientific disciplines.

ABSTRACT Objective Ilizarov technology is highly effective in addressing complex orthopedic challenges. This study aims to describe our experience with distraction osteogenesis in managing bone tumors in the lower extremity, focusing on composite bone defects and associated complications. Methods A retrospective clinical study was conducted to analyze patients with primary bone tumors who underwent distraction osteogenesis using the Ilizarov method from 2010 to 2020. Some young children received epiphyseal distraction and bone transport as part of their sarcoma surgical treatment. Additionally, external fixation, bone transport, or limb lengthening were employed to address complex postoperative complications associated with bone tumors. The clinical outcomes assessed included the patient's general information, the location of bone defects, the length of bone repair, the status of bone healing, and limb function. Results Eleven patients were followed up for an average of 66 months (range, 24–132 months). The average length of repaired bone defects was 13 cm (range, 2.5–32 cm). The cohort comprised three females and eight males, with ages at presentation ranging from 6 to 42 years (mean, 18 years). The sites of involvement included the distal femur (n = 4), femoral diaphysis (n = 3), proximal tibia (n = 2), and the distal tibia (n = 2). Nine patients were diagnosed with osteosarcoma, while one presented with Ewing's sarcoma and another with a giant cell tumor of bone. Three young children were successfully treated with epiphyseal stretching; however, one patient experienced treatment failure. Additionally, seven patients underwent external fixation to address complex postoperative complications, including infection, bone defects, and limb shortening. At the last follow‐up, with the exception of one failure, the average Musculoskeletal Tumor Society (MSTS) limb function scores for the remaining 10 patients were 25 (range, 21–30). Three months post‐fixator removal, the Asociación Latinoamericana de Oncología (ASAMI) bone score was rated as excellent in 63.6% (7/11) of patients, whereas the ASAMI function score was excellent in 36.4% (4/11) and good in 54.5% (6/11) of cases. Conclusion The Ilizarov method demonstrates some clinical value in the resection and reconstruction of bone tumors, as well as in the management of postoperative complications associated with such tumors.

Abstract Background Dengue fever, an acute insect‐borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear. Methods We used single‐cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single‐cell sequencing results. Results Our result showed CTLs were significantly activated in the severe liver injury group but the immune function‐related signal pathway was down‐regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF‐β signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice. Conclusions In this study, single‐cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

The discovery of the ‘Einstein’ monotile represents one of the most significant advancements in geometry in 2023, prompting research across multiple disciplines. This paper proposes a phased array with a limited beam scanning range based on the ‘Einstein’ monotile (Hat polykite), characterized by low grating lobe levels and high aperture efficiency. The proposed phased array reduces implementation complexity compared to periodic subarrays and enhances engineering practicality relative to other aperiodic tiles, particularly in load-bearing lattice configurations. Two examples of Hat polykite-based phased arrays are presented in this paper. Example A presents a sparse phased array, where each element is embedded within a Hat polykite, optimized for a maximum grating lobe level of −15 dB. Example B features a subarray comprising eight antenna elements based on the Hat polykite. This configuration achieves 90% aperture efficiency while keeping the maximum grating lobe level below −14 dB within an ±18° main beam scanning range.

Abstract Background Dense deposit disease (DDD) is a rare renal disorder major affecting adolescents and children, characterized by an absence of distinctive clinical symptoms. Its coexistence with other renal conditions complicates both diagnosis and treatment in clinical practice. Case presentation We described a 15-year-old male adolescent presenting with nephrotic syndrome as the initial manifestation, with urinalysis indicating significantly elevated protein and erythrocytes. Unexpectedly, the renal pathological biopsy of the patient exhibited strong positivity for both IgA and C3, characterized by petaloid deposition of C3 along glomerular capillary loops and the glomerular mesangial region, as well as linear deposition in Bowman’s capsule and portions of the renal tubular basement membrane. Consequently, the patient was diagnosed with both DDD and IgA nephropathy. The presence of both in a single patient may result in more intricate pathogenic pathways. Conclusions This specific case elucidates the pathological characteristics of both diseases while investigating the intricate connections and lesion correlations that may occur between them, offering novel insights into their pathogenesis.

Abstract Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures. Epithelial cells in EOCC exhibited a notable dual immunological phenotype, characterized by immune-suppressive properties driven by elevated CXCL production, alongside immune-stimulatory features linked to heightened HLA molecule expression. CD4 + and CD8 + T cells in LOCC demonstrated a heightened activation state, while NK cells exhibited diminished cytotoxicity. Macrophages in LOCC displayed enhanced polarization towards both M1 and M2 phenotypes, along with dendritic cells showing augmented antigen-presenting capacity. Regarding cancer-associated fibroblasts (CAFs), EOCC was enriched with inflammatory CAFs, whereas LOCC harbored a higher proportion of antigen-presenting CAFs. These findings reveal the multifaceted immune heterogeneity between EOCC and LOCC, underscoring the imperative for age-tailored immunotherapeutic strategies.

Abstract Endotypes are characterized by the immunological, inflammatory, metabolic, and remodelling pathways that explain the mechanisms underlying the clinical presentation (phenotype) of a disease. Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease caused by COL7A1 pathogenic variants. Although underscored by animal studies, the endotypes of human RDEB are poorly understood. To fill this gap, we apply systems immunology approaches using single-cell high-dimensional techniques to capture the signature of peripheral immune cells and the diversity of metabolic profiles in RDEB adults, sampled outside of any opportunistic infection and active cancer. Our study, demonstrates the particular inflammation and immunity characteristics of RDEB adults, with activated / effector T and dysfunctional natural killer cell signatures, concomitant with an overall pro-inflammatory lipid signature. Artificial intelligence prediction models and principal component analysis stress that RDEB is not solely confined to cutaneous issues but has complex systemic endotypes marked by immune dysregulation and hyperinflammation. By characterising the phenotype-endotype association in RDEB adults, our study lays the groundwork for translational interventions that could by lessening inflammation, alleviate the everlasting suffering of RDEB patients, while awaiting curative genetic therapies.

Abstract While self-assembled material based inverted perovskite solar cells have surpassed power conversion efficiencies of 26%, enhancing their performance in large-area configurations remains a significant challenge. In this work, we report a self-assembled material based hole-selective layer 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid, with a π-expanded conjugation. The enhanced intermolecular π–π interactions facilitate the self-assembly of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid molecules to form an ordered bilayer with a hydrophilic surface, which passivates the buried perovskite interface defect and enables high-quality and large-area perovskite preparation, while simultaneously enhancing interfacial charge extraction and transport. The certified efficiency of 4-(7H-dibenzo[c,g]carbazol-7-yl)phenyl)phosphonic acid based small-area (0.0715 cm2) device is 26.39% with high stability. Furthermore, a certified efficiency of 25.21% is achieved for a 99.12 mm2 large area device.

Abstract Macular degeneration is a leading cause of irreversible vision loss, significantly impacting quality of life. To enhance clinical practice and reduce the risk of drug-related macular degeneration, we analyzed drug-related trends using real-world data. Disproportionality analysis of adverse event reports from the FDA Adverse Event Reporting System (FAERS, 2004–2023) identified 67,683 cases involving 1402 drugs. Among these, 42 drugs were linked to significant risks, including treatments for breast cancer (tamoxifen, raloxifene, anastrozole, letrozole) and diabetes (insulin lispro, insulin human). The BCPNN algorithm revealed that 45.2% (19/42) of these drugs had the strongest associations with macular degeneration, with pentosan polysulfate sodium, travoprost, and tolterodine being the highest-risk drugs. Lifitegrast, nicotine, and travoprost were associated with the shortest onset times for ocular adverse events. Among drug classes, glucocorticosteroids were linked to the most rapid onset of ocular side effects (P

Abstract Background Laparoscopic radical gastrectomy has been reported to be associated with substantial trauma and pain. This study compared the impact of ultrasound-(US)-guided, bilateral, double-injection intertransverse process block (ITPB) on postoperative analgesia with subcostal transversus abdominis plane block (TAPB) in patients who were undergoing laparoscopic radical gastrectomy. Methods Sixty-two patients who were undergoing laparoscopic radical gastrectomy surgery under general anesthesia were included. These patients were randomized to either the ITPB group or the TAPB group. Patients in the ITPB group received a double-shot US-guided bilateral ITPB at the thoracic level T6/7 and T9/10 level using ropivacaine (0.3%, 15 mL). Patients in the TAPB group received bilateral subcostal TAPB one injection per side using ropivacaine (0.3%, 30 mL). All patients used a BIS-guided combined intravenous and inhalation anesthesia. The primary outcome was defined as postoperative morphine-equivalent consumption during the first 24 h. Results The study recruited 62 patients (31 in each group) for the analysis. A comparatively less postoperative opioid consumption was observed in the ITPB group compared with the subcostal TAPB group within the first 24 h postoperatively (mean [standard deviation-(SD)] morphine-equivalent dose): 27.8 (5.7) mg vs 31.2 (4.4) mg, P

Abstract Background Although many studies shown that the risk of congenital heart disease (CHD) was closely related to genetic and environmental factors, the exact mechanism was still unclear. This study was to assess the association of maternal folic acid supplementation (FAS), the 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) gene polymorphisms in offspring and their interaction effects with the risk of CHD and its subtypes. Methods A case-control study was conducted on 595 children with CHD and 605 healthy child controls. The multivariate logistic regression model was used to assess the association of maternal FAS, offspring MTRR gene polymorphisms and their interaction effects with CHD and its subtypes. Results This study shown that maternal FAS was significantly associated with a reduced risk of CHD (OR = 0.55, 95%CI: 0.36–0.83) and its subtypes including ASD (OR = 0.25, 95%CI: 0.14–0.45), VSD (OR = 0.42, 95%CI: 0.27–0.64), and CTD (OR = 0.23, 95%CI: 0.09–0.59) in offspring. Offspring MTRR gene polymorphisms at rs162048 (GG vs. AA: OR = 2.05, 95%CI: 1.35–3.13), rs1802059 (AA vs. GG: OR = 5.13, 95%CI: 2.15–12.23; GA vs. GG: OR = 1.81, 95%CI: 1.35–2.43), rs10380 (TT vs. CC: OR = 2.27, 95%CI: 1.20–4.31) and rs1801394 (GG vs. AA: OR = 1.58, 95%CI: 1.02–2.42) were significantly associated with the risk of CHD, and similar results were also found for three subtypes of CHD. Additionally, a statistically significant interaction effect between maternal FAS and offspring MTRR gene polymorphism at rs1802059 was observed (OR = 0.38, 95%CI: 0.15–0.94). Among children who had a variant genotype at rs1802059, the risk of CHD was significantly decreased when their mother used folate for this pregnancy compared with mothers not using folate. Conclusions In those of Chinese descent, maternal FAS and offspring MTRR gene polymorphisms are significantly associated with the risk of CHD and its three subtypes. Furthermore, maternal FAS may help to offset some of risks of CHD due to offspring MTRR genetic variants. However, more studies with prospective designs and larger samples are needed to confirm our findings. Trial registration Registration number: ChiCTR1800016635; Registration time: 14/06/2018.

Summary: Purpose: It aims to validate the mediating role of felt obligation between inclusive leadership and the caring behavior of clinical nurses using a structural equation model. Methods: All of the nurses were assessed with the general information questionnaire, caring behavior scale, felt obligation scale and inclusive leadership questionnaire. AMOS 21.0 was used to construct the structural equation model and analyze the mediating effect of felt obligation, and Bootstrap method was used to test the mediating effect model. Results: The total scores of caring behavior, felt obligation and inclusive leadership were 125.25 ± 18.31, 21.38 ± 3.36 and 62.95 ± 11.95 respectively. Felt obligation played a partial mediating role in the relationship between inclusive leadership and caring behavior of nurses, and the mediating effect accounted for 43.5%. Conclusions: Felt obligation plays a partial mediating effect between inclusive leadership and caring behavior of nurses. Nursing managers can adopt the leadership concept of inclusive leadership to enhance the level of felt obligation of nurses, so as to better improve the caring behavior of nurses.

Abstract Post-transplant diabetes mellitus (PTDM) is a common complication following renal transplantation, and its incidence has been gradually increasing in recent years, posing a significant public health challenge. Managing PTDM is complex, as studies suggest that it involves changes in the microbial flora across multiple organs. Recent research highlights the critical role of gut flora metabolism in the development of diabetes among post-renal transplant patients. This paper reviews the alterations in gut flora observed in PTDM patients and explores how gut flora influences PTDM. These findings may offer new perspectives on targeting gut flora metabolites for the prevention and treatment of PTDM.

Abstract Purpose To assess bone mineral density (BMD) in middle-aged individuals in Shanghai, in order to improve awareness of osteopenia and osteoporosis screening. Methods The clinical data of 1107 permanent residents of Shanghai aged 40–60 years were collected using a random cluster sampling method. Osteoporosis questionnaire survey and BMD test were conducted. Mann-Whitney U and Chi-square test were used to compare sex, age and body mass index at different stages of bone mass, and Pearson test was used to conduct correlation analysis. Logistic regression was used to analyze the influencing factors. Results The detection rates of osteopenia and osteoporosis were 59% and 12.5% respectively, and bone mineral density was correlated with sex, age, and body mass index (P

Abstract CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045. HB0045 is a 1:1 mixture of two humanized monoclonal IgG1 antibodies (mAbs), HB0038 and HB0039. The cocktail not only harnesses the advantages of its parental mAbs in enzyme inhibition but also shows a significantly greater capability of promoting T cell proliferation in vitro. Structural analyses show that HB0045 effectively locks the CD73 dimer in a “partially open” non-active conformation through a double lock mechanism. In various animal models of syngeneic and xenograft tumors, HB0045 inhibits tumor growth more potently than the single mAbs. Collectively, our findings provide functional and structural insights into the mechanism of a CD73-targeting antibody cocktail.

ObjectiveTo develop a theoretical grading method for foodborne disease risk assessment during major events in Beijing, using a major sports event as an example, and to provide references and experiences for foodborne disease risk assessment during other major events in China. MethodsAccording to the World Health Organization's list of foodborne diseases, combined with the foodborne diseases monitored by the Beijing Foodborne Disease Surveillance System during the major sports event from 2016 to 2020 (November to April of the following year) as risk factors, the risk levels of foodborne diseases in the key population and the general population of a major sports event in Beijing were evaluated using the risk matrix method and the Borda count method. ResultsA total of 25 foodborne disease risk factors were identified in 3 major categories and 7 subcategories. The risk levels of foodborne disease in both the key population and the general population were concentrated in the high risk (H), moderate risk (M), and low risk (L) levels. For the key population, there were 5 H-level risk factors (20%), 11 M-level risk factors (44%), and 9 L-level risk factors (36%), of which rodenticides and tetrodotoxin poisoning were the most important risk factors. For the general population, there were 4 H-level risk factors (16%), 6 M-level risk factors (24%), and 15 L-level risk factors (60%). Among them, norovirus and kidney bean poisoning were the most important risk factors. ConclusionsFoodborne disease risk assessment for major events should be based on the characteristics of the event, previous experience with major events, and foodborne disease surveillance data from the same period. Prevention measures should focus on high and medium risk factors and those at the top of the Borda ordinal, and carry out monitoring and testing in the procurement, storage, processing and other links of raw materials, formulate recipes scientifically, do a good job in personnel health and training, and prevent cross-contamination.

The decline in ovarian estrogen production is known to have detrimental health consequences and negatively affect the quality of life in menopausal women. Increasing estradiol levels is key to preventing disease in menopausal women. In this study, Lactobacillus gasseri CCFM1255 isolated from healthy infants was found to have a positive effect on estradiol production in ovariectomized rats. CYP19, the key enzyme catalysing the conversion of androgens into estrogens, was upregulated in adipose tissue upon CCFM1255 treatment. Untargeted metabolome analysis and targeted metabolite detection were used to identify the key metabolites altered by CCFM1255 treatment. CCFM1255 treatment significantly improved the serum concentration of glutamine (Gln). A significantly positive correlation was observed between serum Gln and estradiol concentrations. CCFM1255 treatment reshaped the structure of the gut microbiome, which was correlated with certain changes in serum metabolite concentrations. These results indicate that the provision of CCFM1255 as a dietary supplement may be an effective strategy to alleviate menopausal symptoms by increasing circulating estradiol.

The effects of the co-inoculation of Debaryomyces hansenii separately with 3 lactic acid bacteria (LAB), Lactobacillus sakei, Lactobacillus plantarum and Lactobacillus curvatus, on the taste and odour profiles of dry sausages were investigated. The co-inoculated sausages showed higher free amino acid and organic acid contents than the non-inoculated control and sausages inoculated with D. hansenii alone. Meanwhile, the sausages inoculated with D. hansenii + L. plantarum, D. hansenii + L. sakei and D. hansenii + L. curvatus had the highest contents of aldehydes, esters and alcohols, respectively. The results of electronic tongue, electronic nose and sensory evaluation demonstrated that compared with the sausage inoculated with D. hansenii, the sour taste and floral odour increased and the fatty odour decreased in the sausage inoculated with D. hansenii + L. sakei; this was more favourable for the development of a desirable flavour in sausages. Moreover, the partial least squares regression analysis indicated that 10 taste and 33 odour compounds were mainly responsible for the differences in the flavour profiles among the sausages. Overall, these findings contributed to a more comprehensive understanding of the formation of sensory characteristics in dry sausages co-inoculated with yeast and LAB.

Abstract Candidate phyla radiation (CPR) constitutes a substantial fraction of bacterial diversity, yet their survival strategies and biogeochemical roles in brackish-saline groundwater remain unknown. By reconstructing 399 CPR metagenome-assembled genomes (MAGs) and 2007 non-CPR MAGs, we found that CPR, affiliated with 44 previously proposed phyla and 8 putative novel phyla, played crucial roles in maintaining the microbial stability and complexity in groundwater. Metabolic reconstructions revealed that CPR participated in diverse processes, including carbon, nitrogen, and sulfur cycles. Adaption of CPR to high-salinity conditions could be attributed to abundant genes associated with heat shock proteins, osmoprotectants, and sulfur reduction, as well as their cooperation with Co-CPR (non-CPR bacteria co-occurred with CPR) for metabolic support and resource exchange. Our study enhanced the understanding of CPR biodiversity in high-salinity groundwater, highlighting the collaborative roles of self-adaptive CPR bacteria and their reciprocal partners in coping with salinity stress, maintaining ecological stability, and mediating biogeochemical cycling.

Fuscoporia is a polypore genus of Hymenochaetaceae that causes wood decay, although some species in the genus have medicinal values. Phylogenetic analyses of concatenated ITS1-5.8S-ITS2-nLSU sequence data and morphological features identified three new species, F. eucalypticola, F. resupinata and F. subtropica from Australia, China and Malaysia, and these new species derived from the Fuscoporia ferrea group. These three species are illustrated and described. A key to resupinate species of Fuscoporia without mycelial setae in the world is provided.

Abstract The numerous grainboundaries solid electrolyte interface, whether naturally occurring or artificially designed, leads to non-uniform Li metal deposition and consequently results in poor full-battery performance. Herein, a lithium-ion selective transport layer is reported to achieve a highly efficient and dendrite-free lithium metal anode. The layer-by-layer assembled protonated carbon nitride nanosheets present uniform macroscopical structure without grainboundaries. The carbon nitride with ordered pores in basal plane provides high-speed lithium-ion transport channels with low tortuosity. Consequently, the assembled 324 Wh kg−1 pouch cell exhibits 300 stable cycles with a capacity retention of 90.0% and an average Coulombic efficiency up to 99.7%. The ultra-dense Li metal anode makes current collector-free anode possible, achieving high energy density and long cycle life of a 7 Ah cell (506 Wh kg−1, 160 cycles). Thus, it is proved that a macroscopically uniform interface layer with lithium-ion conductive channels could achieve Li metal battery with promising application potential.

Abstract Background The incidence of adjacent vertebral body re-fracture after percutaneous kyphoplasty (PKP) is associated with a number of variables, of which decreased bone mineral density is one of the major risk factors. Forearm bone mineral density (BMD) measurements are gaining attention because of their convenience and validity, but there is a lack of systematic research on the specific relationship between forearm BMD and the risk of adjacent vertebral re-fracture after PKP. Purpose To investigate the correlation between forearm BMD and the risk of adjacent vertebral re-fracture after PKP in osteoporotic vertebral compression fractures (OVCF) patients. Methods Retrospective evaluation of 198 OVCF patients receiving PKP was conducted in this study. The patients were divided into two groups: the no-fracture group and the re-fracture group, according to whether or not they had undergone vertebral re-fracture. Obtain basic information about the patient's age, sex, body mass index, bone cement leakage, smoking history, diabetes history, and surgical segmentation. Using computed tomography, the mean Hounsfield unit (HU) values for the BMD of the L1 lumbar spine were determined. For the dual-energy X-ray BMD test, the distal one-third lengths of the patient's nondominant forearm's radius and ulna were chosen. Receiver operating characteristic curves were utilized to evaluate the predictive value of forearm BMD versus lumbar CT values for vertebral re-fracture, and univariate and multivariate logistic regression analyses were employed to identify characteristics related with vertebral re-fracture following PKP. Results Re-fracture rate after PKP was 17.2% at a minimum 12-month follow-up. Significant differences were seen between the refracture and non-fracture groups in terms of hypertension, Cobb angle correction, vertebral height recovery rate, intradiscal cement leakage, forearm bone density, and vertebral HU values. In multifactorial logistic regression analysis, forearm bone density (OR 0.821; 95% CI 0.728–0.937, p = 0.008) and HU values (OR 0.815; 95% CI 0.733–0.906, p = 0.005) were independent risk factors for vertebral re-fracture. The area under the curve (AUC) for forearm BMD values and HU values predicting adjacent vertebral re-fracture were 0.956 and 0.967, respectively. Conclusions Forearm BMD is an independent risk factor for re-fracture of adjacent vertebrae after PKP. In addition, forearm BMD, as a valid indicator of postoperative re-fracture after PKP in patients with OVCF, and the HU value of lumbar spine CT were both powerful tools for predicting re-fracture.

Abstract In wireless sensor network, mobile sink is used to collect data from sensor nodes by periodically traversing the network to prevent hotspot problem. However, when sensor nodes generate data non-uniformly, the efficiency of data collection is constrained by rendezvous points and network topology. It becomes more challenging under network energy consumption constraint. Thus, this paper investigates non-uniform data generation in wireless sensor network and proposes an innovative approach: Optimal Clustering and Network Topology for Mobile Sink-Driven Data Collection, called OCNTMS. It focuses on determining optimal rendezvous points and their associated clusters. Through innovative methods such as weight-balanced clustering, cost function optimization, load-balanced link construction, and node forwarding selection, the OCNTMS can efficiently construct link sets within clusters and accurately plan the mobile sink’s traversal of rendezvous points. Simulation results show that the OCNTMS reduces energy consumption by 18% and increases network lifetime by 40% compared with existing approaches under the constraint of non-uniform data generation. This greatly improves the network energy efficiency and data transmission efficiency.

Abstract Background Gastric cancer is one of the most common malignant tumors in the world, with a poor prognosis. HOXC is a family of transcription factors that are up-regulated in gastric cancer tissues. However, the relationship between Homeobox C12 (HOXC12) and gastric cancer is still unclear. Methods TCGA-STAD and HPA data were analyzed to explore HOXC12 level. Kaplan–Meier Plotter was used to analyze the relationship between HOXC12 level and the prognosis of gastric cancer patients. The HOXC12 was knocked down or overexpressed by shRNA or overexpression vector to explore its functions. Cell migration/invasion assays and wound healing assay were used to assess the invasion/migration ability of gastric cancer cells. Western blot and qPCR were used to detect gene expression and the activation of Wnt/β-catenin signaling pathway. Dual-luciferase reporter assay was used to detect the active region bound by HOXC12 in the promoter of Spalt-like transcription factor 4 (SALL4). Results HOXC12 was highly expressed in gastric cancer and was positively correlated with the poor prognosis of gastric cancer patients. HOXC12 promotes the invasion and migration of gastric cancer cells via Wnt/β-catenin signaling pathway. HOXC12 upregulated the transcription of SALL4 by binding to its promoter. HOXC12 was negatively correlated with both the levels of CD8+ T cells and T cell cytotoxicity-related genes. Conclusion HOXC12 promotes the invasion/migration of gastric cancer cells via SALL4/Wnt/β-catenin axis, and is negatively correlated with the infiltration of CD8+ T cells, suggesting HOXC12 as a diagnostic marker and a potential therapeutic target for gastric cancer.

ObjectiveTo analyze the spatiotemporal clustering of anthrax cases in the Ningxia Hui Autonomous Region from 2019 to 2022 and to perform molecular typing of 14 strains of Bacillus anthracis (B. anthracis) isolated during the same period. MethodsData on anthrax cases reported in Ningxia Hui Autonomous Region (Ningxia) from 2019 to 2022 were collected, and spatiotemporal cluster analysis was performed using SaTScan software with districts and counties as units. A total of 14 strains of B. anthracis isolated from local anthrax cases from 2019 to 2021 were subjected to molecular typing analysis using canonical single nucleotide polymorphisms (CanSNPs), twenty-five marker multilocus variable number tandem repeat analysis (MLVA-25), and single nucleotide repeat (SNR-4) methods. ResultsA total of 80 anthrax cases, all of which were cutaneous anthrax, were reported in Ningxia during the 3-year period. SaTScan spatiotemporal cluster analysis revealed a spatiotemporal cluster in north-central Ningxia from 2021 to 2022, with a primary cluster in Yongning county [P < 0.01, relative risk (RR) = 13.83] and secondary clusters in Lingwu city and Litong district (P = 0.022, RR = 3.47). The genetic relationships of the 14 B. anthracis strains isolated during the same period were defined as: A.Br 001/002 subgroup, 6 different MLVA genotypes within A3.b gene cluster, of which 3 common genotypes were defined as 2, 3, and 5 PHANA genotypes, respectively, by SNR-4 analysis; SNR-4 analysis showed 12 SNR genotypes. ConclusionThe incidence of anthrax in Ningxia showed an increasing trend from 2019 to 2022. One of the reasons for the formation of spatiotemporal clusters of anthrax in 2021 – 2022 may be the formation and development of natural foci. Molecular typing revealed that the genetic relationship of the strains isolated in Ningxia from 2019 to 2022 was relatively homogeneous, with abundant genetic diversity within the same genetic relationship.

Alongside the rapid advancement of artificial intelligence technologies, the complexity of society continues to escalate, and the design of multi-agent system rules becomes increasingly crucial, optimize participant engagement and addressing the issue of fairness and equilibrium win rates. The card game Legends of the Three Kingdoms (LTK), as a complex multi-agent system, represents an important abstraction of real-world scenarios, requiring the implementation of proper incentive mechanisms. Based on the mechanism and Stackelberg, this paper optimizes player strategies and system fairness. Firstly, we constructed a multi-agent Stackelberg game model for team battles. Then, we analyzed the impact of decision-making factors on players. Subsequently, we defined three kinds of fairness and improved the incentive mechanism. The results indicate that our mechanism optimizes participants' game behaviors, enhancing fairness among team players. Win rates were improved from 56.2% VS 43.8% to 51.4% VS 48.6%. With three different fairness measures, the win percentage fairness increased by 72 %, and the first elimination fairness increased by about 79 %. Our research provides a reference for understanding and analyzing complex computational models and facilitates the resolution of various resource allocation and system design issues.

Abstract Objective To investigate the effect of pulmonary vein antrum enlargement combined with left atrial roof cryoballoon ablation in patients with persistent atrial fibrillation (PeAF) by analyzing the relationship between left atrial isolation area surface area (ISA) and early postoperative recurrence. Methods 93 patients with PeAF were classified into recurrence and non-recurrence groups according to the results of the 1-year follow-up. Three-dimensional electroanatomical labeling map was constructed and merged with that of the left atrial pulmonary vein CTA, and the ISA and the left atrial surface area (LASA) were measured and analyzed to determine the relationship between ISA/LASA in relation to early postoperative recurrence. Results 93 patients were included and followed up for 1 year with AF-free recurrence rate of 75.3%. The ISA of the recurrence group was lower than that of the non-recurrence group. Left atrial internal diameter (LAD), left common pulmonary vein, the ISA, the ISA/LASA and early-term recurrence had statistical significance in both groups. The factors that significantly predicted early-term recurrence were left common pulmonary vein and the ISA/LASA. ISA/LASA (HR 0, 95% CI 0–0.005, P = 0.008) and left common pulmonary vein trunk (HR 7.754, 95% CI 2.256–25.651, P = 0.001) were the independent risk factors for early recurrence. ROC curve analysis showed that ISA/LASA predicted the best early recurrence after operation with a cut-off value of 15.2%. Conclusion A greater ISA/LASA reduces early recurrence after cryoablation in patients with PeAF. An ISA/LASA of 15.2% may be the best cut-off value for predicting early recurrence after cryoablation for PeAF.

Abstract Liver fibrosis, a chronic and long-term disease, can develop into hepatocellular carcinoma (HCC) and ultimately lead to liver failure. Early diagnosis and effective treatment still face significant challenges. Liver inflammation leads to liver fibrosis through continuous activation of hepatic stellate cells (HSCs) and the accumulation of immune cells. Intracellular communication among various immune cells is important for mediating the inflammatory response during fibrogenesis. Extracellular vesicles (EVs), which are lipid bilayer membrane-enclosed particles naturally secreted by cells, make great contributions to cell-cell communication and the transport of bioactive molecules. Nearly all the cells that participate in liver fibrosis release EVs loaded with lipids, proteins, and nucleic acids. EVs from hepatocytes, immune cells and stem cells are involved in mediating the inflammatory microenvironment of liver fibrosis. Recently, an increasing number of extracellular vesicle-based clinical applications have emerged, providing promising cell-free diagnostic and therapeutic tools for liver fibrosis because of their crucial role in immunomodulation during pathogenesis. The advantages of extracellular vesicle-based therapies include stability, biocompatibility, low cytotoxicity, and minimal immunogenicity, which highlight their great potential for drug delivery and specific treatments for liver fibrosis. In this review, we summarize the complex biological functions of EVs in the inflammatory response in the pathogenesis of liver fibrosis and evaluate the potential of EVs in the diagnosis and treatment of liver fibrosis.

Abstract Purpose Vision-threatening diabetic retinopathy (VTDR) included severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and clinically significant diabetic macular edema (DME). To compare the axial length (AL) and assess its influence on VTDR across different ages. Methods A retrospective cohort study. Medical chart review was performed in 736 consecutive patients with VTDR. The patients were divided into young (≤ 45 years) and elderly group (> 45 years) based on their age at the diagnosis of VTDR. After at least one year of standardized treatments, all eligible patients were followed up. The main outcome measures included the presence of tractional retinal detachment (TRD) involving foveal, final best-corrected visual acuity (BCVA), the development of neovascular glaucoma (NVG), and recurrent vitreous hemorrhage (VH) post-vitrectomy. ALs were compared between two age groups. The impact of AL on clinical outcomes was determined by logistic analyses after controlling for systemic parameters. Results The study included 144 patients ≤ 45 years and 592 patients > 45 years. Young patients had significantly longer AL than elderly participants (23.9 mm vs 23.0 mm, p

Abstract This paper investigates the fixed-time cluster formation tracking (CFT) problem for networked perturbed robotic systems (NPRSs) under directed graph information interaction, considering parametric uncertainties, external perturbations, and actuator input deadzone. To address this complex problem, a novel hierarchical fixed-time neural adaptive control algorithm is proposed based on a hierarchical fixed-time framework and a neural adaptive control strategy. The objective of this study is to achieve accurate CFT of NPRSs within a fixed time. Specifically, we design a distributed observer algorithm to estimate the states of the virtual leader within a fixed time accurately. By using these observers, a neural adaptive fixed-time controller is developed in the local control layer to ensure rapid and reliable system performance. Through the use of the Lyapunov argument, we derive sufficient conditions on the control parameters to guarantee the fixed-time stability of NPRSs. The theoretical results are eventually validated through numerical simulations, demonstrating the effectiveness and robustness of the proposed approach.

Abstract Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2HKO) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1.

Low-temperature pretreatment methods such as hydrothermal carbonization and dry terrefaction can effectively improve the fuel characteristics of biomass, achieving an efficient biomass utilization. Empty fruit bunch (EFB) was selected as the experimental raw material, and was pretreated by hydrothermal carbonization and dry terrefaction in the temperature range of 180−220 ℃, to study the effect of carbonization pretreatment on the physicochemical properties of biomass. The results showed that both hydrothermal carbonization and dry terrefaction could increase the carbon content and heating value of the biomass, reduce the H/C and O/C, and the quality enhancement effect of hydrothermal carbonization was more obvious at the same reaction temperature. A study on the CO2 gasification reaction characteristics of carbonization product pellets was carried out at 800−950 ℃ using large pellet thermogravimetry, and the experimental results showed that the carbon conversion rate of EFB feedstock pellets was only 30% at 800 ℃ for 60 min, but could be up to 100% at 850−950 ℃, and the peak gasification reaction rate of the pellets increased from 0.007%/min at 800 ℃ to 0.042%/min at 950 ℃. When the gasification temperature was 950 ℃, the gasification reactivity of hydrothermal carbon particles, R0.5 (reactivity corresponding to 50% carbon conversion), decreased from 0.034 min−1 for raw material particles to 0.023 min−1 for HT-180, and decreased to 0.011 min−1 when the hydrothermal temperature was increased from 180 ℃ to 220 ℃; the R0.5 of 200 ℃ terrefaction particles was the highest at 0.039 min−1. The analysis of the surface morphology and specific surface area of the granular gasification char at different gasification stages at 950 ℃ proved that the pellets formed by the melting of ash during the gasification process of EFB feedstock and terrefaction pellets adhered to their surfaces, and the pellet pores were clogged in the process of increasing the carbon conversion from 50% to 80%, and the specific surface areas were reduced by 502.40 m2/g and 452.44 m2/g respectively. During the process of increasing carbon conversion from 80% to 98%, the ash pellets gradually fused and coated the surface of the gasification char, resulting in the specific surface area of the pellets to reduce to about 1 m2/g, and the R0.98 (reactivity corresponding to 98% carbon conversion) to reduce to 0.017 min−1 and 0.018 min−1, respectively. The specific surface area of hydrothermal carbon pellets increased by 126.98 m2/g during the increase of carbon conversion from 80% to 98%, which was attributed to the fact that the removal of AAEMs by hydrothermal carbonization alleviated the slagging phenomenon during the gasification of pellets, resulting in no significant change in the reactivity of the pellets for gasification.

BackgroundThe tumor microenvironment plays a crucial role in the progression of both glioma and glioma-induced autoimmune encephalitis. However, there remains a significant lack of effective therapeutic targets for these diseases.MethodWe collected 54 CT images of glioma patients and 54 glioma-induced autoimmune encephalitis patients, respectively. Radiomics features were extracted from tumors and encephalitis regions using Python, followed by dimensionality reduction via random forest and lasso regression, and construction of radiomics-based risk scores. Genomic data matched with clinical information were analyzed to identify key prognostic genes significantly associated with risk scores. Gene expression was validated by immunohistochemistry using our clinical samples. Immune infiltration was evaluated using five algorithms (MCP-counter, EPIC, TIMER, QUANT and IPS). The association between hub genes and immune checkpoint markers as well as immunoregulation-related genes was also analyzed using Spearman correlation.ResultsWe identified 980 radiomics features both in glioma and encephalitis patient images and selected four key features through lasso regression to build a radiomics-based risk score. COL22A1 was strongly correlated with the risk score and identified as the hub prognostic gene. COL22A1 expression was higher in glioblastoma tissues and cell lines, and correlated with clinical factors such as higher age, WHO grade, and IDH mutation status. Immune infiltration analysis indicated associations with diverse immune and stromal cell populations, including CD8+T cells, macrophages, and CAFs. COL22A1 was also positively correlated with immune checkpoints and immune-regulated genes.ConclusionOur study highlights the critical role of COL22A1 in gliomas and glioma-Induced Autoimmune Encephalitis, demonstrating its strong association with poor prognosis and its significant involvement in tumor immune regulation.

BackgroundHeart failure with reduced ejection fraction (HFrEF) affects a substantial portion of the global population, with left ventricular remodeling (LVR) and inflammation identified as key contributors to disease progression. Standardized Rhodiola rosea Injection (SRRI) is a pharmacopoeia-based botanical drug preparation derived from Rhodiola rosea, widely used in China for heart failure treatment. It is standardized in composition and quality control, with known antioxidant, anti-inflammatory, and anti-fibrotic properties. However, comprehensive evaluations of SRRI’s effects on LVR and inflammatory mediators in HFrEF patients are limited.PurposeTo evaluate the effects of SRRI on LVR and inflammatory mediators in patients with HFrEF.MethodsA systematic review and meta-analysis were conducted following PRISMA and Cochrane guidelines. Eight databases were searched for randomized controlled trials (RCTs) on SRRI in HFrEF treatment with studies identified from inception to 31 October 2024. Quality assessment of the included studies was conducted using the Cochrane Collaboration’s risk of bias tool and the modified Jadad scale. Statistical analysis was performed using Stata version 17.0, with sensitivity analyses conducted by sequentially excluding studies to assess the robustness of findings. Publication bias was evaluated using Egger’s test.ResultsTwenty-five RCTs with 2,325 participants were included. SRRI significantly improved LVR, indicated by increased LVEF (MD = 6.81, 95% CI: 5.71 to 7.91, P < 0.00001), reduced LVEDD (MD = −4.37, 95% CI: −5.42 to −3.33, P < 0.00001), and decreased LVESD (MD = −4.48, 95% CI: −5.42 to −3.58, P < 0.00001). Additionally, SRRI effectively reduced inflammatory mediators, including TNF-α (MD = −10.37, 95% CI: −12.96 to −7.78, P < 0.00001), IL-6 (MD = −6.99, 95% CI: −8.88 to −5.11, P < 0.00001), and hs-CRP (MD = −2.58, 95% CI: −3.37 to −1.79, P < 0.00001). SRRI also significantly reduced BNP (MD = −105.10, 95% CI: −132.29 to −77.90, P < 0.00001) and NT-pro BNP (MD = −415.95, 95% CI: −553.00 to −278.89, P < 0.00001). Clinical effectiveness was improved, with no significant increase in adverse reactions (RR = 0.86, 95% CI: 0.59 to 1.25, P = 0.44). Sensitivity analyses confirmed the robustness of these findings, and no significant publication bias was detected.ConclusionSRRI appears to effectively enhance LVR, reduce inflammatory mediators, and improve clinical effectiveness in HFrEF patients while maintaining a favorable safety profile. However, the current evidence is limited by methodological shortcomings, and further well-designed, multicenter RCTs are needed to validate these findings, especially in diverse populations and over long-term treatment durations.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=603884, Identifier CRD42024603884.

High-entropy alloy/graphene composites (HEA/Gr) have shown significant potential in various applications due to their exceptional mechanical properties, particularly their high strength. However, a comprehensive understanding of their strengthening mechanisms is still lacking, which hinders the design of their structures and optimization of their performance. This study systematically investigates the tensile behavior of the equiatomic CoCrFeMnNi HEA and HEA/Gr composite using molecular dynamics simulations, focusing on the microscopic strengthening mechanisms of the reinforcing phase and the low-temperature hardening behavior of the HEA/Gr composite. The results show that the yield strength and elastic modulus of the composite increased by 57.5 % and 19 %, respectively, compared to the HEA. The graphene interface effectively hinders dislocation propagation and enhances dislocation interactions, playing a crucial role in stress transfer and resulting in distinct stress and strain distributions within the matrix. Moreover, the low-temperature hardening mechanisms of the composite were explored. The study reveals that local BCC atomic clusters formed by FCC-BCC phase transition accelerate dislocation nucleation. The compatibility between the FCC and BCC lattice structures facilitates dislocation slip and promotes the interaction of intrinsic stacking faults (ISFs), leading to local stress concentration and increased dislocation entanglement.

Introduction: Pseudomyxoma Peritonei (PMP) is an extremely rare disease characterized by progressive accumulation of mucinous ascites and implants in the peritoneum. We investigated the prognostic value for response to cytoreductive surgery (CRS) or hyperthermic intraperitoneal chemotherapy (HIPEC) and dissected potential beneficial targeted therapy utilizing genomic characteristics. Methods: Whole-exome sequencing (WES) was performed on tissue specimens and matched white blood cells from 81 patients with PMP. The study investigated mutational signatures, profiling, and their correlation with progression-free survival (PFS) and overall survival (OS). Results: Signature 3 (HRD) and signature 15 (dMMR) were dominant. NMF cluster 1, characterized by signature 4, exhibited a worse prognosis. The p53 and TGF-β signaling pathways may contribute as risk factors for worse OS and PFS, respectively. MUC16-mutated patients had worse PFS (P = 0.016) and OS (P = 0.004) compared to wild-type patients. Patients with tumor mutational burden (TMB) > 1(P = 0.026) or alterations in TP53 (P = 0.006) or SMAD4 (P = 0.013) had significantly worse OS compared to those with a TMB < 1 or normal genes. Patients with homologous recombination deficiency (HRD) positivity (P = 0.003) or alterations in TGFBR2 (P = 0.037) experienced worse PFS compared to their respective control groups. Furthermore, NMF cluster1 (P = 0.020), TP53 (P = 0.004), and MUC16 (P = 0.013) were identified as independent prognostic factors for OS, while HRD status (P = 0.003) was independent predictors for PFS in PMP. Conclusions: The study reveals that genomic profiling can serve as a robust tool for identifying prognostic markers in PMP. The identified genomic mutations and signaling pathway offer new avenues for targeted therapies.

Dysfunctional cholesterol metabolism is highly prevalent in patients with hyperuricemia. Both uric acid and cholesterol are independent risk factors for atherosclerosis, contributing to an increased incidence of cardiovascular disease in hyperuricemia. Investigating the pathological mechanisms underlying cholesterol metabolism dysfunction in hyperuricemia is essential. This study identified adenosine and inosine, two major purine metabolites, as key regulators of cholesterol biosynthesis. These metabolites upregulate 3-hydroxy-3-methylglutaryl-CoA. Further mechanistic studies revealed that adenosine/inosine up-regulated the expression of 3-hydroxy-3-methylglutaryl-CoA by activating adenosine A2A receptor via the Srebp-2/Creb axis in hyperuricemia. Additionally, we found that taurine deficiency contributes to cholesterol metabolism dysfunction in hyperuricemia. Taurine administration in hyperuricemia mice significantly reduced cholesterol elevation by inhibiting adenosine A2A receptor. This study provides a promising strategy for treating comorbid hypercholesterolemia and hyperuricemia.

Animal models are indispensable for unraveling the mechanisms underlying post-acute sequelae of COVID-19 (PASC). This review evaluates recent research on PASC-related perturbations in animal models, drawing comparisons with clinical findings. Despite the limited number of studies on post-COVID conditions, particularly those extending beyond three months, these studies provide valuable insights. Three hallmark features of PASC—lung fibrosis, hyperglycemia, and neurological sequelae—have been successfully replicated in animal models, paving the way for mechanistic discoveries and future medical interventions. Although most studies have reported post-COVID conditions within 14–60 days post-infection, they still offer critical reference for future long-term research. This review also explores potential mechanisms of persisting immune misfiring, a key factor in the chronicity of PASC symptoms. Moreover, challenges in modeling PASC are also discussed, including the limited genetic diversity in inbred animal strains and difficulties in accurately identifying PASC-affected individuals. To address these issues, we propose methodological improvements, such as comparing individual animal parameters with control averages and incorporating genetically diverse populations like collaborative cross models. These strategies will enhance the identification and characterization of PASC endotypes in animal studies. By integrating findings from animal models with clinical manifestations of PASC, future research can provide more valuable insights into its mechanisms and support the development of effective therapeutic strategies. Finally, we emphasize the urgent need for longitudinal studies in animal models to fully uncover the mechanisms driving PASC and guide interventions to mitigate its public health impact.

ABSTRACT This study aimed to evaluate the effects of the concomitant administration of TPN171 and alcohol on hemodynamic and pharmacokinetic characteristics in healthy Chinese male subjects. Fifteen eligible subjects were randomly assigned to one of three sequences, each comprising three treatments: Treatment A (placebo +0.5 g/kg alcohol), Treatment B (TPN171 + 0.5 g/kg alcohol), and Treatment C (TPN171 + placebo). Enrolled subjects were administered with 10 mg TPN171 and/or 0.5 g/kg alcohol in fasting state in a randomized crossover design. Blood pressure, pulse rate (PR), blood samples, and breath alcohol test were measured at designated time points for hemodynamic and pharmacokinetic analyses. Compared with 10 mg TPN171 alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol significantly lowered the area under the effect–time curve from 0 to 4 h (AUEC0‐4h) of systolic blood pressure (95% confidence interval [CI]: −29.75 to −0.83, p = 0.039) and significantly increased AUEC0–4h of PR (95% CI: 7.47–28.92, p = 0.003). Compared with 0.5 g/kg alcohol alone, administration of 10 mg TPN171 + 0.5 g/kg alcohol contributed to significantly higher maximal increase of PR (95% CI: 2.78–9.44, p = 0.002) and AUEC0‐4h of PR (95% CI: 1.08–24.52, p = 0.035). Alcohol had no influence on the pharmacokinetics of TPN171, and vice versa. Though the concomitant administration of TPN171 and alcohol induced a more pronounced increase in PR, this did not result in clinical symptoms or heart rate increase‐related adverse events, indicating that the combined use was generally safe and well‐tolerated.

AimsWhether the intraprocedural anticoagulation regimen and activated clotting time (ACT) in pulsed field ablation (PFA) for atrial fibrillation (AF) are the same as those for radiofrequency catheter ablation (RFCA) is currently unknown.Methods and resultsOur retrospective study included 51 paroxysmal AF patients who underwent PFA (PFA group) and were matched with paroxysmal AF patients who underwent RFCA. Nearest-neighbor propensity score matching was performed at a 1:1 ratio (no tolerance to anticoagulant regimens and a tolerance of 0.02 on the CHA2DS2-VASc score, left atrial diameter, and left ventricular ejection fraction). Compared with the RFCA group, the PFA group had a significantly shorter procedure time but a longer fluoroscopy time. In both groups, an initial heparin dose of 110 U/kg was given. The 30-min ACT in the PFA group (240 ± 95.5 s) was shorter than that in the RFCA group (294.4 ± 82.3 s, P = 0.003). The 60-, 90-, and 120-min ACTs were significantly longer in the PFA group. The percentage of 30 min-ACTs in the therapeutic range in the RFCA group (33.3%) was greater than that in the PFA group (15.7%, P = 0.038). The time to achieve the target ACT was longer in the PFA group. There were no differences in the incidence of periprocedural thromboembolism or bleeding events between the two groups.ConclusionsCompared with RFCA, PFA was associated with longer intraprocedural ACTs, shorter initial ACTs, fewer initial ACTs in the therapeutic range, and longer times to achieve the target ACT.

Abstract Aqueous‐phase phosphors are of utmost importance for a myriad of applications. However, the emission wavelengths of the current aqueous organic room‐temperature phosphorescent (RTP) materials are limited to green and red bands, while the blue part is rarely reported, thus limiting the development of a full‐color RTP system. Theoretically, carboxylated benzene is expected to be blue phosphorescence‐emissive, but only green phosphorescence is observed in solid, due to the strong intermolecular π–π stacking that decreases the energy gap. Herein, the use of water‐dispersible layered double hydroxide (ZnAl‐LDH) is proposed for isolating Ph‐(COOH)n and the distance between the adjacent chromophores is confirmed to be larger (≈7.0 Å) than the threshold of π–π interaction. Deep‐blue phosphorescence with a lifetime over 0.1 s, and a maximum luminescence quantum yield of 42%, is harvested in the aqueous phase. The long‐lived deep‐blue phosphorescence is successfully explored for high‐temperature display and luminescent dyes.

BackgroundMild cognitive impairment (MCI) is associated with an increased risk of dementia in older adults. Olfactory impairment may indicate prodromal dementia, yet its underlying mechanisms are not fully understood. This study aimed to investigate the alterations in functional connectivity (FC) of odor-induced olfactory neural circuits in MCI patients.MethodsThe study included 39 MCI patients and 42 normal controls (NCs). All subjects underwent cognitive assessments, olfactory behavior tests, and odor-based functional magnetic resonance imaging (fMRI). Differences in FC within olfactory circuits were analyzed using the generalized psychophysiological interaction (gPPI) method.ResultsMild cognitive impairment patients showed significant cognitive deficits, including lower scores on the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), alongside impairments in episodic memory, visuospatial memory, executive function, language, attention, olfactory threshold, and total olfactory function. Compared to NCs, MCI patients exhibited reduced activation in the bilateral primary olfactory cortex (bPOC) during olfactory stimulation. Odor-induced bPOC activation correlated with olfactory thresholds across the cohort. During odor stimulation, MCI patients showed increased FC from the bPOC to the right anterior frontal lobe, particularly the middle frontal gyrus (MFG) and superior frontal gyrus (SFG). Conversely, FC from the right anterior frontal lobe to the medial temporal cortex, including the fusiform and parahippocampal gyri, was reduced in MCI patients. Increased FC from the bPOC to the right SFG/MFG negatively correlated with episodic memory, while decreased FC to the right fusiform/parahippocampal gyri positively correlated with attention, language ability, and olfactory identification.ConclusionThis study indicates that impaired FC within the primary olfactory cortex (POC)-anterior frontal cortex-medial temporal cortex circuit is a sensitive neuroimaging marker for early MCI identification. The primary dysfunction appears in the POC, suggesting that FC alterations from this region may provide novel diagnostic and therapeutic avenues for early intervention.

BackgroundRapid population aging has prompted most emerging economies to consider introducing long-term care insurance (LTCI) as part of a comprehensive social health protection scheme. China is also in the process of establishing its own LTCI framework. However, the details of the scheme are still being explored in pilot cities, and a long-term solution has yet to be finalized. This study aims to examine the insurance preferences of potential enrollees, providing insights to inform further adjustments to the existing framework.MethodsWe examine discrete choice experiment (DCE) evidence from LTCI and evaluate several relevant attributes, including the elimination period, maximum monthly benefit, out-of-pocket rate, and annual premium. The study uses a mixed logit model to elicit respondents’ preferences and willingness to pay (WTP) for these attributes of LTCI and uses physical health status to assess heterogeneity in responses to insurance choice.ResultsWe found that most respondents would consider purchasing LTCI, with respondents most preferring the following attributes: (1) an out-of-pocket rate of 25%, (2) a maximum monthly benefit level of 2000 CNY (about 296 USD), and (3) a three-month elimination period. In addition, among the control variables, marital status, personal self-rated health, and the number of children were significant to varying degrees.ConclusionThe study can provide a reference for further adjustments to the existing scheme, increasing residents’ willingness to participate in insurance and promoting the sustainable development of long-term care insurance.

Abstract Kawasaki disease (KD) is a severe acute febrile illness and systemic vasculitis that causes coronary artery aneurysms in young children. Platelet hyperreactivity and an aberrant immune response are key indicators of KD; however, the mechanism by which hyperactive platelets contribute to inflammation and vasculopathy in KD remains unclear. A cytokine‐mediated positive feedback loop between KD platelets and monocytes is identified. KD platelet–monocyte aggregates (MPAs) are mediated by an initial interaction of P‐selectin (cluster of differentiation 62P, CD62p) and its glycoprotein ligand 1 (PSGL‐1). This is followed by a coordinated interaction of platelet glycoprotein (GP)Ibα with monocyte CD11b. Monocyte‐activated platelets initiate transforming growth factor (TGF)β1 release, which results in nuclear localization of nuclear factor kappaB in monocytes, therefore, driving the phenotypic conversion of classical monocytes (CD14+CD16−) into proinflammatory monocytes (CD14+CD16+). The platelet‐activated monocytes release interleukin‐1 and tissue necrotic factor‐α, which promote further platelet activation. KD‐induced inflammation and vasculopathy are prevented by inhibiting the components of this positive feedback loop. Notably, mice deficient in platelet TGFβ1 show less MPA and CD14+CD16+ monocytes, along with reduced inflammation and vasculopathy. These findings reveal that platelet–monocyte interactive proteins (CD62p/PSGL‐1 and (GP)Ibα/CD11b) and cytokine mediators (platelet TGFβ1) are potential biomarkers and therapeutic targets for KD vasculopathy.