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Abstract Background Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients’ recovery. Methods In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2–0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2–0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome. Results Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P 0.05). Conclusion Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin. Trial registration ChiCTR2200056891,first registered on 22/02/2022.

Abstract Rest–activity behavior clusters within individuals to form patterns are of significant importance to their intrinsic capacity (IC), yet they have rarely been studied. A total of 1253 community-dwelling older adults were recruited between July and December 2021 based on the baseline survey database of the Fujian Prospective Cohort Study on Aging. Latent profile analysis was used to identify profiles of participants based on rest–activity behaviors, whereas logistic regression analysis was carried out to investigate the relationship between profiles and IC. We identified three latent profiles including: (1) Profile 1—labeled “Gorillas”: High physical activity (PA), moderate sedentary behaviors (SB), screen time (ST) and sleep (n = 154, 12%), (2) Profile 2—labeled as “Zebras”: Moderate PA, low SB, ST and high sleep (n = 779, 62%), and (3) Profile 3—labeled as“Koalas”: High SB, ST, low PA and sleep (n = 320, 26%). Logistic regression revealed a negative correlation between low IC and the “Gorillas” profile (β = − 0.945, P

Abstract Background and purpose In the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC). Methods This real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI. Results 120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group. Conclusion The results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

Abstract The analysis of genomic variations in offspring after implantation has been infrequently studied. In this study, we aim to investigate the extent of de novo mutations in humans from developing fetus to birth. Using high-depth whole-genome sequencing, 443 parent-offspring trios were studied to compare the results of de novo mutations (DNMs) between different groups. The focus was on fetuses and newborns, with DNA samples obtained from the families’ blood and the aspirated embryonic tissues subjected to deep sequencing. It was observed that the average number of total DNMs in the newborns group was 56.26 (54.17–58.35), which appeared to be lower than that the multifetal reduction group, which was 76.05 (69.70–82.40) (F = 2.42, P = 0.12). However, after adjusting for parental age and maternal pre-pregnancy body mass index (BMI), significant differences were found between the two groups. The analysis was further divided into single nucleotide variants (SNVs) and insertion/deletion of a small number of bases (indels), and it was discovered that the average number of de novo SNVs associated with the multifetal reduction group and the newborn group was 49.89 (45.59–54.20) and 51.09 (49.22–52.96), respectively. No significant differences were noted between the groups (F = 1.01, P = 0.32). However, a significant difference was observed for de novo indels, with a higher average number found in the multifetal reduction group compared to the newborn group (F = 194.17, P

Abstract Background High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. Case presentation A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. Conclusions Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

Assembly buildings, in the context of the low-carbon transformation of the construction industry, achieve superior outcomes in terms of carbon emission reduction, enhancement of building uniformity, and optimization of resource utilization as compared to traditional buildings. However, the supply chain for assembly building is marked by a significant susceptibility to risk and a need for timely fulfillment of requirements. This paper examines the risk of disruption and capacity limitations in the assembly building supply chain resulting from supply disruptions. It establishes a three-tier supply chain for assembly buildings, including primary component suppliers, backup suppliers, assembly manufacturers, and retailers. The study compares the optimal decision-making and coordination strategies of the supply chain members under centralized, decentralized, and joint agreements. The supply chain dual-source procurement decision coordination model is constructed by incorporating capacity constraints and analyzing the effects of supply disruption probability, repurchase coefficient, revenue sharing coefficient, cost, and other parameters on the expected profits of the supply chain members using arithmetic simulation. Research has indicated that when the likelihood of a disturbance occurring rises, the anticipated financial gain for the main provider decreases, while the predicted financial gain for the secondary supplier increases. The implementation of a collaborative agreement between the assembly maker and the parts backup provider would result in much greater anticipated profits compared to the decentralized decision-making approach. The impact of the revenue sharing coefficient on the predicted earnings of retailers and assembly manufacturers is more significant compared to the repurchase coefficient. The selection bias between NA and NB techniques under capacity constraints mostly arises from the assertiveness of the wholesale asking prices of inexpensive component suppliers, leading assembly manufacturers to increasingly prefer the NA option. This paper's research successfully achieves the contractual coordination of the assembly building supply chain, enhances the resilience of the assembly building supply chain, and promotes the long-term sustainable development of the assembly building supply chain.

Abstract New coupling scheme substrate‐integrated waveguide (SIW) diplexers based on dual‐mode cavities are proposed for millimetre‐wave applications. Dual‐mode SIW cavities are simultaneously employed in common input and coupling cavity to produce filtering transmission poles and transmission zero (TZ). A common input SIW cavity with two orthogonal modes is employed instead of the traditional T‐junction for circuit miniaturisation, insertion‐loss reduction, and intrinsically high isolation. A critical dual‐mode SIW cavity with diagonally distributed modes has been employed in each channel to realise a controllable stopband TZ for high selectivity of passband's skirt. To further improve channel isolation and passbands' selectivity, a SIW diplexer based on dual‐ and single‐mode cavities is proposed, and four‐pole responses for each passband channel are designed. For the verification, two millimetre‐wave diplexers have been fabricated and tested.

Increasing customer apprehensions regarding the security and nutritional value of agricultural goods are compelling governments and industries to implement traceable, transparent, and reputable logistics management systems. Blockchain-based agricultural logistics management systems guarantee the permanence of data once it is uploaded but cannot cope with the risk of data being falsified before uploading to the blockchain. In this work, we developed a collaborative game model between government bodies and agricultural enterprises based on the evolutionary game theory and explored the influencing factors of enterprises following the rules to share the real traceability information through numerical simulation using MATLAB. The findings show that government incentives and penalties promote positive behavior, and consumer and media supervision contribute to supply chain transparency, but firms tend to share truthful information only when it benefits them. This study builds upon existing research on the impact of social variables on both members' decision-making behavior. It highlights the positive roles of consumers and the media in the supervision of agricultural product traceability, which can help to raise public awareness of social responsibility and thus promote positive interaction in the market.

Rorippa palustris Besser 1821, a species of Brassicaceae, is widely distributed around the world and used for both food and traditional Chinese medicinal purposes. Despite the plant’s significance, its genetic diversity must be better understood. In this study, we have successfully assembled and characterized a complete plastome of R. palustris, marking a significant advancement toward comprehending its genetic composition. The plastome is 154,674 bp long and harbors 128 genes, including 83 protein-coding genes, 37 tRNA genes, and eight rRNA genes. Our phylogenomic analysis indicated that R. palustris is closely related to R. curvipes. These findings are crucial for conserving and utilizing this important plant species. They also highlight the potential for future research into the evolution and preservation of R. palustris, which could be advantageous in pharmaceutical applications.

Background Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P

The resource utilization of calcium carbide residue (CCR) and rice husk ash (RHA) is helpful to save resources and alleviate environmental pollution. In this research, CCR and RHA were used to modify soft clay, and the resonant column test was conducted to explore its small-strain dynamic characteristics. The micro-mechanism of CCR-RHA modified soft clay (CRSC) was investigated by using scanning electron microscopy, X-ray diffraction and mercury intrusion tests. The findings demonstrated that the dynamic shear modulus of the CRSC increased with the increase of RHA content and confining pressure, but decreased with the increase of shear strain. In contrast, the damping ratio presents the opposite change law. The Hardin-Drnevich (H-D) model was used to fit the dynamic shear modulus/maximum dynamic shear modulus (G/Gmax)-shear strain γ and the damping ratio D-shear strain γ. As confining pressure increased, Gmax increased but Dmax dropped in CRSC specimens with the same RHA content. The changes of the fitted G/Gmax-γ curve could be divided into progressively decrease stage and rapid decrease stage, while the changes of the fitted D-γ curve could be separated into linear stage and slow stage, with the same turning point γ = 10−4. Microscopic tests revealed that the incorporation of CCR and RHA helped to promote the hydration reaction, and the generated hydration products such as calcium silicate hydrate were able to enhance the integrity and compactness of the CRSC. The results of this research putfward solid foundation for the application of CCR-RHA in the modification of soft soil.

In this study, Hypermesh and LS-DYNA numerical simulation software are used to build a multi domain coupling model of natural gas pipeline, including soil, pipeline, TNT explosive and air domain, and the non-reflection boundary conditions are set for the model. The TNT equivalent method is used to convert the physical explosion amount of natural gas pipeline into 1387.38 kg TNT explosive amount. The simulation results show that the physical explosion of pipeline forms an approximate elliptical crater with a width of 12.68 m and a depth of 4.12 m; the TNT equivalent of the model is corrected by comparing the crater simulation value and the size value of the crater calculated by the PRCI empirical formula under the same laying condition, and the correction coefficient is selected as 0.9, and the corrected TNT equivalent is 1248.64 kg; the modified model crater size is 3.72 m deep and 12.66 m wide, compared with the crater size obtained from the field test, the error of crater depth and width calculated by the modified model simulation is 5.7% and 15.5% respectively.

Abstract Hierarchical Bi2Fe4O9/BiOI S-scheme nanoflower heterostructures are prepared by hydrothermal method, which exhibit exceptional photo-piezoelectric catalytic performance. The tight binding between the sheets ensures the efficient electron transport, and provides a large interface area and adequate reaction sites for photo-piezoelectric catalytic reactions. At the same time, because the water flow in the water body produces hydraulic shear force on the material, the material produces piezoelectric effect. Bi2Fe4O9/BiOI exhibit a remarkable degradation efficiency of 99.4% for tetracycline and a hydrogen production rate of 4089.36 µmol h−1 g−1. The observed behavior can be explained by the combined influence of the formation of S-scheme structure and the process of photo-piezoelectric catalysis, confirmed by in-situ XPS, transient/steady-state fluorescence and piezoelectric response force test. The excellent stability of the material suggests its possible use in the sectors of energy and environment. This work introduces novel concepts for the future advancement of photo-piezoelectric synergistic catalysis.

Abstract Background Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. Methods Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. Results During 2006–2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. Conclusions Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.

Abstract Background Diabetic nephropathy (DN) is a common complication of diabetes mellitus, and Prolyl 4-Hydroxylase Subunit Beta (P4HB) expression is increased in high glucose (HG)-induced renal tubular epithelial cells (TECs). But it’s role in HG-induced TECs remains to be elucidated. Methods The HK-2 cells were induced using HG and transfected with SiRNA-P4HB. DCFH-DA staining was utilized for the detection of cellular levels of ROS. WB and immunofluorescence were utilized to detect the expression of P4HB, epithelial-mesenchymal transition (EMT), fibrosis, and TGFβ/SMAD3-related proteins in HK-2 cells. Online databases were utilized for predicting the interaction target of P4HB, and immunoprecipitation (IP) experiments were employed to validate the binding of P4HB with the target. SiRNA and overexpression vectors of target gene were used to verify the mechanism of action of P4HB. Results HG induced an increase in the expression of P4HB and TGFβ, p-SMAD3, and ROS in HK-2 cells. Furthermore, HG downregulated the expression of E-cadherin and upregulated the expression of N-cadherin, Vimentin, α-SMA, Fibronectin, Collagen IV, SNAIL, and SLUG in HK-2 cells. Interfering with P4HB significantly reversed the expression of these proteins. Database predictions and IP experiments showed that P4HB interacts with PRMT1, and the expression of PRMT1 was increased in HG-induced HK-2 cells. Interfering with PRMT1 inhibited the changes in expression of EMT and fibrosis related proteins induced by HG. However, overexpression of PRMT1 weakened the regulatory effect of P4HB interference on the EMT, fibrosis, and TGFβ/SMAD3-related proteins in HK-2 cells. Conclusion P4HB regulated the TGFβ/SMAD3 signaling pathway through PRMT1 and thus participates in HG-induced EMT and fibrosis in HK-2 cells.

Abstract This study investigated the influence of different temperatures (35℃ High temperature and average indoor ambient temperature of 25℃) and lactic acid bacterial additives (Lactiplantibacillus plantarym, Lentilactobacillus buchneri, or a combination of Lactiplantibacillus plantarym and Lentilactobacillus buchneri) on the chemical composition, fermentation quality, and microbial community of alfalfa silage feed. After a 60-day ensiling period, a significant interaction between temperature and additives was observed, affecting the dry matter (DM), crude protein (CP), acid detergent fiber (ADF), and neutral detergent fiber (NDF) of the silage feed (p < 0.05). Temperature had a highly significant impact on the pH value of the silage feed (p 0.05), while the inoculation of additives had a significant effect on lactic acid, acetic acid, and butyric acid (p > 0.05). As for the dynamic changes of microbial community after silage, the addition of three kinds of bacteria increased the abundance of lactobacillus. Among all treatment groups, the treatment group using complex bacteria had the best fermentation effect, indicating that the effect of complex lactic acid bacteria was better than that of single bacteria in high temperature fermentation. In summary, this study explained the effects of different temperatures and lactic acid bacterial additives on alfalfa fermentation quality and microbial community, and improved our understanding of the mechanism of alfalfa related silage at high temperatures.

Abstract The metaverse represents a transformative landscape for human interaction, promising an immersive digital ecosystem where users can create, share, and experience resources in novel ways. Within this context, the establishment of Beidou Navigation Satellite System (BDS) commons in the metaverse is an exciting prospect that could revolutionize knowledge sharing, governance, and sustainability. This paper explores the potential of the metaverse as a platform for building BDS commons, focusing on three key dimensions: resource sharing, collaborative governance, and sustainable development. We examine the current state of research, identify existing gaps, and propose directions for future inquiries to fully harness the potential of the metaverse for global resource sharing and collective action.

Abstract Objective This study aimed to evaluate the impact of adding 4 mg estradiol valerate to progesterone for luteal support on pregnancy rates in IVF cycles following a long protocol with reduced luteal serum estradiol levels post-hCG triggering. Design, setting, and participants The prospective randomized controlled trial was conducted at a public tertiary hospital reproductive center with 241 patients who experienced a significant decrease in serum estrogen levels post-oocyte retrieval. Interventions Participants received either a daily 4 mg dose of estradiol valerate in addition to standard progesterone or standard progesterone alone for luteal support. Results The ongoing pregnancy rate did not show a significant difference between the E2 group and the control group (56.6% vs. 52.2%, with an absolute rate difference (RD) of 4.4%, 95% CI -0.087 to 0.179, P = 0.262). Similarly, the live birth rate, implantation rate, clinical pregnancy rate, early abortion rate, and severe OHSS rate were comparable between the two groups. Notably, the E2 group had no biochemical miscarriages, contrasting significantly with the control group (0.0% vs. 10.7%, RD -10.7%, 95% CI -0.178 to -0.041, P = 0.000). In the blastocyst stage category, the clinical pregnancy rate was notably higher in the E2 group compared to the control group (75.6% vs. 60.8%, RD 14.9%, 95% CI 0.012 to 0.294, P = 0.016). Conclusion Adding 4 mg estradiol valerate to progesterone for luteal support does not affect the ongoing pregnancy rate in embryo transfer cycles using a long protocol with a significant decrease in serum estradiol levels after hCG triggering. However, it may reduce biochemical miscarriages and positively impact clinical pregnancy rates in blastocyst embryo transfer cycles. Trial registration ChiCTR1800020342.

Y2O3–Al2O3–ZrO2 composite ceramic powders are an important structural and functional material. The agglomeration problem in the ceramic powder drying process must be resolved to prepare high-quality ceramic powder, and choosing the right drying techniques can significantly lessen ceramic powder agglomeration. Y2O3–Al2O3–ZrO2 ceramic powder was dried using microwave drying. The drying kinetics of the powders were examined with their initial mass, moisture content, and microwave power. As microwave power, beginning moisture content, and initial mass rose, the average drying rate also increased, according to the experimental data. To better characterize the microwave drying process, the drying data were fitted and analyzed using four thin-layer drying kinetic models, namely Quadratic Model, Modified Page, Wang and Singh, and Two-term exponential. The outcomes demonstrate the good fitting effect of the Modified Page model and the compliance of the fitting parameters with the law. The samples before and after drying were characterized by Fourier transform infrared spectroscopy. Calculating the diffusion coefficient by Fick's second law shows that the effective diffusion coefficient of Y2O3–Al2O3–ZrO2 composite ceramic powder is 5.6 × 10−11 m2/s when the initial moisture content is 5%, the microwave heating power is 560 W, and the initial mass is 25 g. The activation energy for microwave drying of Y2O3–Al2O3–ZrO2 ceramic powders was calculated to be 22.83 W/g according to the Arrhenius formula. This paper aims to provide a theoretical basis and rich experimental data for the study of microwave drying of Y2O3–Al2O3–ZrO2 composite ceramic powder.

Abstract Background High Intensity Macro and Micro Focused Ultrasound ( HIFU) is a safe and effective method for the treatment of skin laxity. However, the application of high-intensity focused ultrasound energy on eyelids has been associated with potential ocular complications including traumatic cataract, iridocyclitis, and conjunctival hemorrhage, among others. Case presentation A 40-year-old female developed blurred vision in her left eye after receiving HIFU treatment on binocular eyelids, and her left far vision was 20/66. The examination revealed left eye iris depigmentation and conjunctival hemorrhage. Both eyes exhibited multiple white streaking or tadpole-shaped opacities in the lenses. Conclusion Excessive ultrasonic energy generated by HIFU can cause protein denaturation, leading to conditions such as traumatic cataract, visual impairment, injuries to the iris and conjunctiva when applied to the eyes. We recommend that individuals undergoing cosmetic treatment in the periorbital region should be highly aware of the possible ocular side effects.

Abstract We aimed to investigate the preventive effect of vitamin D2 on COVID-19 and the improvement of symptoms after COVID-19 infection. The study recruited 228 health care workers who tested negative PCR or antigen for COVID-19. Subjects were randomly allocated to vitamin D2 or non-intervention at a ratio 1:1. Subjects recorded PCR or antigen tests and the symptoms of COVID-19 twice a week during the follow-up visit. The concentration of serum 25-hydroxyvitamin D (25(OH)D), C-reaction protein (CRP), complement component C1q and inflammatory cytokines were measured. The rates of COVID-19 infection were 50.5% in the vitamin D2 group and 52.4% in the non-intervention group (P = 0.785). There was no difference in the COVID-19 symptoms between the two groups. The mean 25(OH)D level significantly increased from 14.1 to 31.1 ng/mL after administration (P 30 ng/mL) and deficient groups (

Abstract Bound states in the continuum (BICs), referring to spatially localized bound states with energies falling within the range of extended modes, have been extensively investigated in single-particle systems, leading to diverse applications in photonics, acoustics, and other classical-wave systems. Recently, there has been theoretical interest in exploring many-body BICs in interacting quantum systems, which necessitate the careful design of impurity potentials or spatial profiles of interaction. Here, we propose a type of many-body BICs localized at boundaries, which can be purely induced by the uniform onsite interaction without requiring any specific design of impurity potential or nonlocal interaction. We numerically show that three or more interacting bosons can concentrate on the boundary of a homogeneous one-dimensional lattice, which is absent at single- and two-particle counterparts. Moreover, the eigenenergy of multi-boson bound states can embed within the continuous energy spectra of extended scattering states, thereby giving rise to interaction-induced boundary many-body BICs. Furthermore, by mapping Fock states of three and four bosons to nonlinear circuit networks, we experimentally simulate boundary many-body BICs. Our findings enrich the comprehension of correlated BICs beyond the single-particle level, and have the potential to inspire future investigations on exploring many-body BICs.

Abstract Neovaginas are surgically constructed to correct uterovaginal agenesis in women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or as part of gender-affirming surgery for transfeminine individuals. Understanding the assembly of the neovaginal microbiota is crucial for guiding its management. To address this, we conducted a longitudinal study on MRKH patients following laparoscopic peritoneal vaginoplasty. Our findings reveal that the early microbial assemblage exhibited stochastic characteristics, accompanied with a notable bloom of Enterococcus faecalis and genital Mycoplasmas. While both the pre-surgery dimple microbiota and the fecal microbiota constituted the primary species pool, the neovaginal microbiota developed into a microbiota that resembled that of a normal vagina at 6–12 months post-surgery, albeit with a bacterial vaginosis (BV)-like structure. By 2–4 years post-surgery, the neovaginal microbiota had further evolved into a structure closely resembling with the homeostatic pre-surgery dimple microbiota. This concords with the development of the squamous epithelium in the neovagina and highlights the pivotal roles of progressive selective forces imposed by the evolving neovaginal environment and the colonization tropism of vaginal species. Notably, we observed that strains of Lactobacillus crispatus colonizing the neovagina primarily originated from the dimple. Since L. crispatus is generally associated with vaginal health, this finding suggests potential avenues for future research to promote its colonization.

Abstract Cobalt phthalocyanine immobilized on carbon nanotube has demonstrated appreciable selectivity and activity for methanol synthesis in electrocatalytic CO2/CO reduction. However, discrepancies in methanol production selectivity and activity between CO2 and CO reduction have been observed, leading to inconclusive mechanisms for methanol production in this system. Here, we discover that the interaction between cobalt phthalocyanine molecules and defects on carbon nanotube substrate plays a key role in methanol production during CO2/CO electroreduction. Through detailed operando X-ray absorption and infrared spectroscopies, we find that upon application of cathodic potential, this interaction induces the transformation of the planar CoN4 center in cobalt phthalocyanine to an out-of-plane distorted configuration. Consequently, this potential induced structural change promotes the transformation of linearly bonded *CO at the CoN4 center to bridge *CO, thereby facilitating methanol production. Overall, these comprehensive mechanistic investigations and the outstanding performance (methanol partial current density over 150 mA cm−2) provide valuable insights in guiding the activity and selectivity of immobilized cobalt phthalocyanine for methanol production in CO2/CO reduction.

Abstract Deep vein thrombosis (DVT) is a leading cause of morbidity and mortality after trauma. Here, we integrate plasma metabolomics and proteomics to evaluate the metabolic alterations and their function in up to 680 individuals with and without DVT after trauma (pt-DVT). We identify 28 metabolites and 2 clinical parameter clusters associated with pt-DVT. Then, we develop a panel of 9 metabolites (hexadecanedioic acid, pyruvic acid, L-Carnitine, serotonin, PE(P-18:1(11Z)/18:2(9Z,12Z)), 3-Hydroxycapric acid, 5,6-DHET, 3-Methoxybenzenepropanoic acid and pentanenitrile) that can predict pt-DVT with high performance, which can be verified in an independent cohort. Furthermore, the integration analysis of metabolomics and proteomics data indicates that the upregulation of glycolysis/gluconeogenesis-TCA cycle may promote thrombosis by regulating ROS levels in red blood cells, suggesting that interfering with this process might be potential therapeutic strategies for pt-DVT. Together, our study comprehensively delineates the metabolic and hematological dysregulations for pt-DVT, and provides potential biomarkers for early detection.

Abstract Background Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. Objective To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. Methods The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. Results The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P

Abstract Background Insulin resistance (IR) is prevalent in individuals undergoing peritoneal dialysis (PD) and is related to increased susceptibility to coronary artery disease and initial peritonitis. In recent investigations, correlations have been found between indices of IR and the incidence of all-cause mortality in various populations. However, such correlations have not been detected among individuals undergoing PD. Hence, the present study’s aim was to explore the connections between IR indices and the incidence of all-cause mortality in PD patients. Methods Peritoneal dialysis patients (n = 1736) were recruited from multiple PD centres between January 2010 and December 2021. Cox proportional hazards and restricted cubic spline regression models were used to evaluate the connections between the triglyceride–glucose (TyG) index, triglyceride–glucose/body mass index (TyG–BMI), and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and the occurrence of all-cause mortality. All three IR indices were integrated into the same model to assess the predictive stability. Furthermore, a forest plot was employed to display the findings of the subgroup analysis of PD patients. Results Overall, 378 mortality events were recorded during a median follow-up time of 2098 days. Among PD patients, a higher TyG index, TyG–BMI, and TG/HDL-C ratio were identified as independent risk factors for all-cause mortality according to Cox proportional hazards analyses (hazard ratio (HR) 1.588, 95% confidence interval (CI) 1.261–2.000; HR 1.428, 95% CI 1.067–1.910; HR 1.431, 95% CI 1.105–1.853, respectively). In a model integrating the three IR indices, the TyG index showed the highest predictive stability. According to the forest plot for the TyG index, no significant interactions were observed among the subgroups. Conclusion Significant associations were found between the TyG index, TyG–BMI, and TG/HDL-C ratio and the incidence of all-cause mortality among PD patients. The TyG index may be the most stable of the three surrogate IR markers. Finally, a correlation was identified between IR and the risk of all-cause mortality in patients undergoing PD.

Abstract Background The 15q11.2 BP1-BP2 microdeletion syndrome is associated with developmental delays, language impairments, neurobehavioral disorders, and psychiatric complications. The aim of the present study was to provide prenatal and postnatal clinical data for 16 additional fetuses diagnosed with the 15q11.2 BP1-BP2 microdeletion syndrome in the Chinese population. Methods A total of 5,789 pregnancy women that underwent amniocentesis were enrolled in the present study. Both karyotype analysis and chromosomal microarray analysis (CMA) were conducted on these subjects to detect chromosomal abnormalities and copy number variants (CNVs). Whole exome sequencing (WES) was performed to investigate sequence variants in subjects with clinical abnormalities after birth. Results Sixteen fetuses with 15q11.2 BP1-BP2 microdeletion were identified in the present study, with a detection rate of 0.28% (16/5,789). The 15q11.2 BP1-BP2 microdeletion fragments ranged from 311.8 kb to 849.7 kb, encompassing the NIPA1, NIPA2, CYFIP1, and TUBGCP5 genes. The follow-up results regarding pregnancy outcomes showed that five cases opted for pregnancy termination, while the remaining cases continued with their pregnancies. Subsequent postnatal follow-up indicated that only one case with the 15q11.2 BP1-BP2 microdeletion displayed neurodevelopmental disorders, demonstrating an incomplete penetrance rate of 9.09% (1/11). Conclusion The majority of fetuses with the 15q11.2 microdeletion exhibit typical features during early childhood, indicating a low penetrance and mild impact. Nonetheless, pregnancies involving fetuses with the 15q11.2 microdeletion require thorough prenatal counseling. Additionally, enhanced supervision and extended postnatal monitoring are warranted for those who choose to proceed with their pregnancies.

Abstract Background Breakthrough cancer pain (BTcP) has a negative impact on patients’ quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. Methods The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). Results A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p

Using Taraxacum kok-saghyz Rodin (TKS) roots as the raw material, the liquid-solid ratio, ultrasonic power, extraction temperature, and extraction time were selected as experimental factors. On the basis of single factor experiments, the response surface methodology was used to optimize the ultrasonic-assisted extraction process of polyphenols from the TKS roots. The in vitro antioxidant and hypoglycemic activity of the polyphenols extracted from TKS roots were measured. The results showed that the optimal extraction conditions were liquid-solid ratio of 33:1 mL/g, ultrasonic power of 270 W, extraction temperature of 61 ℃, and extraction time of 31 min. Under these conditions, the yield of polyphenols from TKS roots was 1.46%±0.03%. The in vitro activity test showed that the half inhibitory concentrations (IC50) of polyphenol extracts on DPPH and ABTS+ radicals were 54.06 and 39.27 µg/mL, respectively, the IC50 values for α-amylase and α-glucosidase were 133.26 and 50.22 µg/mL, respectively. This indicated that the polyphenols from TKS roots had strong antioxidant and hypoglycemic activities in vitro. This study can provide theoretical basis for the comprehensive development and utilization of TKS.

Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01–1.21, P-trend = 0.012; HR = 1.23 in the Kailuan cohort, 95% CI: 1.01–1.51, P-trend = 0.036). Elevated glucose (>7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07–2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02–1.27) in the UK Biobank cohort (P-heterogeneity = 0.014). Elevated glucose (>7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04–1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.

Background: As a physiological function of body, immunity can maintain health by identifying itself and excluding others. With economic development and increasingly fierce social competition, the number of sub-healthy population is gradually increasing, and the most basic problem exposed is human hypoimmunity. Hypoimmunity can be manifested as often feeling tired, catching colds, mental depression, etc. In order to enhance immunity, eating healthy foods with the effect of enhancing immunity may become an effective choice. KRG has pharmacological effects of enhancing immunity. Because the screening and evaluation method of immune population are not unified, there are relatively few KRG immunity tests for sub-health population. It is of great significance to study the effect of KRG on people with hypoimmunity to improve sub-health status. Methods: This was a 180-day, randomized, double-blind, placebo-controlled clinical trial. According to the trial scheme design, 119 qualified subjects were included and randomly divided into the test group taking KRG and the placebo control group. Subjects need to check safety indicators (blood pressure and heart rate, blood routine, liver and kidney function, urine routine and stool routine) and efficacy indicators (main and secondary) inspection at baseline, efficacy indicators inspection during the mid-term of the test (90th days of administration), safety and efficacy indicators inspection after the test (180th days of administration). Results: After the test, the safety indicators of placebo control group and KRG test group were basically within the normal range, and there is no significant difference in fireness score between the two groups. Through follow-up interviews, it was found that the subjects in the test group and the control group had no adverse reactions and allergic reactions such as nausea, flatulence, diarrhea, and abdominal pain during the test period. Self-comparison of the test group, the results of the main efficacy indicators: (1) immune related health scores were significantly improved in the mid-term and after the test (P

ABSTRACT: Streptococcus thermophilus is a common starter in yogurt production and plays an important role in the dairy industry. In this study, a galactose-positive (Gal+) mutant strain, IMAU20246Y, was produced using the chemical mutagen N-methyl-N′-nitro-N-nitrosoguanidine (NTG) from wild-type S. thermophilus IMAU20246, which is known to have good fermentation characteristics. The sugar content of milk fermented by either the mutant or the wild type was determined using HPLC; metabolism of lactose and galactose was significantly increased in the mutant strain. In addition, we used response surface methodology to optimize components of the basic M17 medium for survival ratio of the mutant strain. Under these optimal conditions, the viable counts of mutant S. thermophilus IMAU20246Y reached 4.15 × 108 cfu/mL and, following freeze-drying in the medium, retained cell viability of up to 67.42%. These results are conducive to production of a high-vitality starter culture and development of “low sugar, high sweetness” dairy products.

Background: Osteocytes are the main stress-sensing cells in bone. The substances secreted by osteocytes under mechanical loading play a crucial role in maintaining body homeostasis. Osteocytes have recently been found to release exosomes into the circulation, but whether they are affected by mechanical loading or participate in the regulation of systemic homeostasis remains unclear. Methods: We used a tail-suspension model to achieve mechanical unloading on osteocytes. Osteocyte-specific CD63 reporter mice were used for osteocyte exosome tracing. Exosome detection and inhibitor treatment were performed to confirm the effect of mechanical loading on exosome secretion by osteocytes. Co-culture, GW4869 and exosome treatment were used to investigate the biological functions of osteocyte-derived exosomes on brown adipose tissue (BAT) and primary brown adipocytes. Osteocyte-specific Dicer KO mice were used to screen for loading-sensitive miRNAs. Dual luciferase assay was performed to validate the selected target gene. Results: Firstly, we found the thermogenic activity was increased in BAT of mice subjected to tail suspension, which is due to the effect of unloaded bone on circulating exosomes. Further, we showed that the secretion of exosomes from osteocytes is regulated by mechanical loading, and osteocyte-derived exosomes can reach BAT and affect thermogenic activity. More importantly, we confirmed the effect of osteocyte exosomes on BAT both in vivo and in vitro. Finally, we discovered that let-7e-5p contained in exosomes is under regulation of mechanical loading and regulates thermogenic activity of BAT by targeting Ppargc1a. Conclusion: Exosomes derived from osteocytes are loading-sensitive, and play a vital role in regulation on BAT, suggesting that regulation of exosomes secretion can restore homeostasis. The translational potential of this article: This study provides a biological rationale for using osteocyte exosomes as potential agents to modulate BAT and even whole-body homeostasis. It also provides a new pathological basis and a new treatment approach for mechanical unloading conditions such as spaceflight.

In non-small cell lung cancer (NSCLC), as an improtant oncogenic driver gene, epidermal growth factor receptor exon 20 insertion (EGFR ex20ins) has a unique protein structure and is primarily drug-resistant to traditional EGFR-tyrosine kinase inhibitors (EGFR-TKIs). In recent years, exploration of targeted therapy for EGFR ex20ins has never stopped. Firstly Mobocertinib and Amivantamab obtained approval from U.S. Food and Drug Administration (FDA) for EGFR ex20ins mutant NSCLC patients, then other drugs, such as Sunvozertinib, made breakthroughs and combination therapies also obtained gains. Multi-pronged measures are hopeful to overcome EGFR ex20ins drug resistance. As mentioned above, it’s definitely important to gain deeper understanding of molecular mechanism of EGFR ex20ins and assess effect and difference between novel drugs. This review is devoted to make a summary about newest achievement so to provide valuable reference about precise therapy for patients with EGFR ex20ins.

Avian Pasteurella multocida infection, can cause serious economic losses to the poultry industry every year. The inactivated vaccines of avian Pasteurella multocida are used to prevent infection. Increasing the cell density of avian Pasteurella multocida is the key to the application of these inactivated vaccines. This can be achieved by controlling the feeding strategy. This study aimed to achieve high-cell-density cultivation of avian Pasteurella multocida by applying an appropriate medium and a rational feeding strategy based on viable cell growth and dissolved oxygen level variation during a fermentation process. An optimized medium suited for the growth of avian P. multocida was used. Meanwhile, besides the online real-time determination of viable cell density, the concentration of glucose was maintained at 1.5 g/L using a glucose-stat feeding strategy after 2 h. The selected nutrient mixture, including yeast extract, tryptone, betaine, VB1, and VH, was fed using a dissolved oxygen feedback feeding strategy after 4 h. As a result, the viable cell density and cell count of avian P. multocida under optimized conditions were increased to OD600: 9.38 and 4.58×1010 CFU/mL, which were higher by 7.27 and 7.26 times than those under the original conditions, respectively.

Abstract The occurrence of debris flow events in small-scale watersheds with dense vegetation in mountainous areas that result in significant loss of life and missing individuals challenges our understanding and expertise in investigating and preventing these disasters. This has raised concerns about the occurrence of large debris flow disasters from small watersheds. This study focused on a catastrophic debris flow that took place in Longtou Gully (0.45 km2) in Tianquan County, Ya’an City on 25 September 2021, which resulted in 14 deaths and missing individuals. Through comprehensive field investigations, high-precision remote sensing data analyses, and numerical simulations, we analyzed the triggering mechanisms and dynamic processes of this event. Our results indicate that the convergence hollow at the channel head exhibited higher hydraulic conditions during rainfall compared to gentle slopes and convex terrains, leading to the instability of colluvial soil due to the expansion of the saturated zone near the soil–bedrock interface. The entrainment of material eroded from the channel resulted in an approximately 4.7 times increase in volume, and the channel scarp with a height of about 200 m amplified the destructive power of the debris flow. We emphasize the need to take seriously the possibility of catastrophic debris flows in small-scale watersheds, with colluvial deposits in hollows at the channel head under vegetation cover that serve as precursor material sources, and the presence of channel scarps formed by changes in the incision rate of the main river, which is common in the small watershed on both sides. This study provides insights for risk assessment of debris flows in small-scale catchments with dense vegetation cover in mountainous areas, highlighting the importance of vigilance in addressing disasters in small-scale catchments, particularly in regions with increasing human–environment conflicts.

Abstract Background We evaluated the influence of different partial carbon dioxide pressure (PaCO2) levels on organ perfusion in patients with respiratory failure receiving pressure-support ventilation with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Methods In this twelve patients prospective study, ECMO gas-flow was decreased from baseline (PaCO2

Abstract Rapid diagnosis of human T-cell lymphotropic virus (HTLV) type-I and -II infections are essential for timely and cost-effective disease interventions. MP Diagnostics ASSURE HTLV-I/II Rapid Test was developed for the rapid detection of anti-HTLV-I/II antibodies in patients’ serum, plasma, and whole blood specimens. ASSURE HTLV-I/II Rapid Test employed MP Biomedicals’ proprietary HTLV-I/II Trifusion recombinant antigen conjugated with gold nanoparticles and HTLV-I / HTLV-II recombinant antigens immobilized on the nitrocellulose membrane to detect total HTLV-I and HTLV-II antibodies. The overall performance of the ASSURE HTLV-I/II Rapid Test was found to be 99.42% sensitivity (95% Confidence Interval, 98.32–99.88%) and 100% specificity (95% Confidence Interval, 99.58–100.00%) in the tested clinical samples, including a total of 518 HTLV-I/II positive specimens (396 HTLV-I infection, 97 HTLV-II infection and 25 HTLV-I/II dual infection) and 872 HTLV negative clinical specimens consisting of 691 healthy donor samples, 116 potentially cross-reactive samples, and 65 samples with interfering substances. The ASSURE HTLV-I/II Rapid Test can effectively be deployed as a screening tool in any prevalence studies, blood banks or organ transplant centres.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract This study aimed to investigate the current hope levels in patients with primary liver cancer by analyzing the risk indicators of hope levels, constructing and validating a novel hope score-based predictive model. A total of 206 patients with primary liver cancer admitted to the hepato-pancreato-biliary surgery department of a tertiary hospital from October 2020 to June 2021 were included. The Herth Hope Index was utilized to assess hope levels, and based on the questionnaire results, the patients were categorized into low-hope (≤ 30 points) and high-hope (> 30 points) groups. Single-factor analysis and logistic multivariate regression analysis were conducted to explore the factors influencing hope levels in patients with primary liver cancer. A nomogram was plotted, and a risk prediction model for hope levels in these patients was developed. The predictive performance of the nomogram model was evaluated using calibration plots, the Hosmer–Lemeshow test, and other relevant assessments. Total of 206 patients participated in the questionnaire survey, with 82 patients (39.81%) categorized as belonging to the low-hope group. The results of the single-factor analysis showed statistically significant differences (all P 0.05). The observed and expected values generated by the Hosmer–Lemeshow test were plotted as a scatter plot with a fitted linear trend, showing good consistency between the predictive model and actual risk. The constructed predictive model developed in this study exhibited good predictive capability for assessing the hope levels of patients with primary liver cancer. This model can assist clinical staff in rapidly identifying the psychological risk of low hope levels in patients, thereby providing valuable insights for the timely implementation of proactive management measures.

Abstract Muscle quality index (MQI) is a novel indicator reflecting the quality of skeletal muscles. The association between MQI and the development of advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is unknown. We investigated the association of low MQI with advanced fibrosis among adults with NAFLD using a nationally representative sample of the US population. Adults with NAFLD who participated in the National Health and Nutrition Examination Survey (NHANES) 2011–2014 were included. Sex-specific standard was used to define low and extremely low MQI. Univariate and multivariate logistic regressions were used to assess the association between MQI level and advanced fibrosis. In the study, 3758 participants with NAFLD were included. The prevalence of low and extremely low MQI was 11.7% (95% CI 10.4–13.0%) and 2.2% (95% CI 1.6–2.8%), respectively. Among these participants, 96 were assessed to have advanced fibrosis. Individuals with low [(odds ratio (OR) 2.45, 95% confidence interval (CI) 1.22–4.91)] and extremely low MQI (OR 10.48, 95% CI 3.20–34.27) were associated with advanced fibrosis in multivariable analysis. A linear trend relationship was also observed between MQI level and the risk of advanced fibrosis (P trend = 0.001). Subgroup and sensitivity analyses yielded similar results to the main analyses. Decreased MQI is highly prevalent, and is associated with an increased risk of advanced fibrosis in adult US population with NAFLD.

Abstract This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0–100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

Abstract In today’s globalized agricultural system, information leakage of agricultural biological risk factors can lead to business risks and public panic, jeopardizing corporate reputation. To solve the above problems, this study constructs a blockchain network for agricultural product biological risk traceability based on agricultural product biological risk factor data to achieve traceability of biological risk traceability data of agricultural product supply chain to meet the sustainability challenges. To guarantee the secure and flexible sharing of agricultural product biological risk privacy information and limit the scope of privacy information dissemination, the blockchain-based proxy re-encryption access control method (BBPR-AC) is designed. Aiming at the problems of proxy re-encryption technology, such as the third-party agent being prone to evil, the authorization judgment being cumbersome, and the authorization process not automated, we design the proxy re-encryption access control mechanism based on the traceability of agricultural products’ biological risk factors. Designing an attribute-based access control (ABAC) mechanism based on the traceability blockchain for agricultural products involves defining the attributes of each link in the agricultural supply chain, formulating policies, and evaluating and executing these policies, deployed in the blockchain system in the form of smart contracts. This approach achieves decentralization of authorization and automation of authority judgment. By analyzing the data characteristics within the agricultural product supply chain to avoid the malicious behavior of third-party agents, the decentralized blockchain system acts as a trusted third-party agent, and the proxy re-encryption is combined with symmetric encryption to improve the encryption efficiency. This ensures a efficient encryption process, making the system safe, transparent, and efficient. Finally, a prototype blockchain system for traceability of agricultural biological risk factors is built based on Hyperledger Fabric to verify this research method’s reliability, security, and efficiency. The experimental results show that this research scheme’s initial encryption, re-encryption, and decryption sessions exhibit lower computational overheads than traditional encryption methods. When the number of policies and the number of requests in the access control session is 100, the policy query latency is less than 400 ms, the request-response latency is slightly more than 360ms, and the data uploading throughput is 48.7 tx/s. The data query throughput is 81.8 tx/s, the system performance consumption is low and can meet the biological risk privacy protection needs of the agricultural supply chain. The BBPR-AC method proposed in this study provides ideas for achieving refined traceability management in the agricultural supply chain and promoting digital transformation in the agricultural industry.

Abstract A combined model was developed using contrast-enhanced CT-based radiomics features and clinical characteristics to predict liver fibrosis stages in patients with chronic liver disease (CLD). We retrospectively analyzed multiphase CT scans and biopsy-confirmed liver fibrosis. 160 CLD patients were randomly divided into 7:3 training/validation ratio. Clinical laboratory indicators associated with liver fibrosis were identified using Spearman's correlation and multivariate logistic regression correlation. Radiomic features were extracted after segmenting the entire liver from multiphase CT images. Feature dimensionality reduction was performed using RF-RFE, LASSO, and mRMR methods. Six radiomics-based models were developed in the training cohort of 112 patients. Internal validation was conducted on 48 randomly assigned patients. Receptor Operating Characteristic (ROC) curves and confusion matrices were constructed to evaluate model performance. The radiomics model exhibited robust performance, with AUC values of 0.810 to 1.000 for significant fibrosis, advanced fibrosis, and cirrhosis. The integrated clinical-radiomics model had superior diagnostic efficacy in the validation cohort, with AUC values of 0.836 to 0.997. Moreover, these models outperformed established biomarkers such as the aspartate aminotransferase to platelet ratio index (APRI) and the fibrosis 4 score (FIB-4), as well as the gamma glutamyl transpeptidase to platelet ratio (GPR), in predicting the fibrotic stages. The clinical-radiomics model holds considerable promise as a non-invasive diagnostic tool for the assessment and staging of liver fibrosis in the patients with CLD, potentially leading to better patient management and outcomes.

Abstract Purpose The most appropriate time of primary tumor radiotherapy in non-small cell lung cancer(NSCLC) with EGFR-TKIs remains unclear. The aim of this study was to investigate the effect of the time factor of primary tumor radiotherapy on long-term overall survival(OS)and provide a theoretical basis for further clinical research. Patients and methods In total, 238 patients with EGFR-TKIs and OS ≥ 12 months were statistically analysed. Patients were grouped: the D group without primary tumor radiotherapy and the R group with it.The R group were divided into three groups according to the interval between the start of EGFR-TKIs and the start of primary tumor radiotherapy: R0 − 30(

Abstract Colorectal cancer is one of the most common cancers around the world, which is a severe threat to people’s health. SMAD4 belongs to the dwarfin/SMAD family, which plays a crucial role in TGF-β and BMP signal pathways. As the molecular characterization of colon cancer patients following SMAD4 mutations remains unclear, we integrated multi-omics data of SMAD4 mutant patients to reveal the profile of molecular characterization of SMAD4 mutation. A missense mutation is the most common mutant type of SMAD4. Patients with SMAD4 mutation had worse survival. Tumor tissues from patients carrying the SMAD4 mutation showed a reduction in various immune cells, such as CD4 + memory T cells and memory B cells. Many differential genes were identified compared to the SMAD4 mutation-free group and could be significantly enriched for tumor- and immune-related signaling pathways. In addition, the mutant group had different drug sensitivities than the non-mutant group.

Abstract Halophyte shrubs, prevalent in arid regions globally, create saline fertile islands under their canopy. This study investigates the soil microbial communities and their energy utilization strategies associated with tamarisk shrubs in arid ecosystems. Shotgun sequencing revealed that high salinity in tamarisk islands reduces functional gene alpha-diversity and relative abundance compared to bare soils. However, organic matter accumulation within islands fosters key halophilic archaea taxa such as Halalkalicoccus, Halogeometricum, and Natronorubrum, linked to processes like organic carbon oxidation, nitrous oxide reduction, and sulfur oxidation, potentially strengthening the coupling of nutrient cycles. In contrast, bare soils harbor salt-tolerant microbes with genes for autotrophic energy acquisition, including carbon fixation, H2 or CH4 consumption, and anammox. Additionally, isotope analysis shows higher microbial carbon use efficiency, N mineralization, and denitrification activity in tamarisk islands. Our findings demonstrate that halophyte shrubs serve as hotspots for halophilic microbes, enhancing microbial nutrient transformation in saline soils.

Phosphorylation, the most extensive and pleiotropic form of protein posttranslation modification, is central to cellular signal transduction. Throughout the extensive co-evolution of plant hosts and viruses, modifications to phosphorylation have served multiple purposes. Such modifications highlight the evolutionary trajectories of viruses and their hosts, with pivotal roles in regulation and refinement of host-virus interactions. In plant hosts, protein phosphorylation orchestrates immune responses, enhancing the activities of defense-related proteins such as kinases and transcription factors, thereby strengthening pathogen resistance in plants. Moreover, phosphorylation influences the interactions between host and viral proteins, altering viral spread and replication within host plants. In the context of plant viruses, protein phosphorylation controls key aspects of the infection cycle, including viral protein functionality and the interplay between viruses and host plant cells, leading to effects on viral accumulation and dissemination within plant tissues. Explorations of the nuances of protein phosphorylation in plant hosts and their interactions with viruses are particularly important. This review provides a systematic summary of the biological roles of the proteins of plant viruses carrying diverse genomes in regulating infection and host responses through changes in the phosphorylation status. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background The dimerizable Cre recombinase system (DiCre) exhibits increased leaky activity in Cryptosporidium, leading to unintended gene editing in the absence of induction. Therefore, optimization of the current DiCre technique is necessary for functional studies of essential Cryptosporidium genes. Methods Based on the results of transcriptomic analysis of Cryptosporidium parvum stages, seven promoters with different transcriptional capabilities were screened to drive the expression of Cre fragments (FKBP-Cre59 and FRB-Cre60). Transient transfection was performed to assess the effect of promoter strength on leakage activity. In vitro and in vivo experiments were performed to evaluate the leaky activity and cleavage efficiency of the optimized DiCre system by polymerase chain reaction (PCR), nanoluciferase, and fluorescence analyses. Results The use of promoters with lower transcriptional activity, such as pcgd6_4110 and pcgd3_260, as opposed to strong promoters such as pActin, pα-Tubulin, and pEnolase, reduced the leakage rate of the system from 35–75% to nearly undetectable levels, as verified by transient transfection. Subsequent in vitro and in vivo experiments using stable lines further demonstrated that the optimized DiCre system had no detectable leaky activity. The system achieved 71% cleavage efficiency in vitro. In mice, a single dose of the inducer resulted in a 10% conditional gene knockout and fluorescent protein expression in oocysts. These fluorescently tagged transgenic oocysts could be enriched by flow sorting for further infection studies. Conclusions A DiCre conditional gene knockout system for Cryptosporidium with good cleavage efficiency and reduced leaky activity has been successfully established. Graphical Abstract