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Abstract A new control approach based on fuzzy sliding mode control (FSMC) is proposed to regulate the chaotic vibration of an axial string. Hamilton’s principle is used to formulate the nonlinear equation of motion of the axial translation string, and the von Kármán equations are used to analyse the geometric nonlinearity. The governing equations are nondimensionalized as partial differential equations and transformed into a nonlinear 3-dimensional system via the third-order Galerkin approach. An active control technique based on the FSMC approach is suggested for the derived dynamic system. By using a recurrent neural network model, we can accurately predict and effectively apply a control strategy to suppress chaotic movements. The necessity of the suggested active control method in the regulation of the nonlinear axial translation string system is proven using different chaotic vibrations. The results show that the study of the chaotic vibrations of axially translating strings requires nonlinear multidimensional dynamic systems of axially moving strings; the validity of the proposed control strategy in controlling the chaotic vibration of axially moving strings in a multidimensional form is demonstrated.

Abstract The aim of this study was to investigate whether triglyceride glucose-body mass index (TyG-BMI) plays a mediating role between obstructive sleep apnoea syndrome (OSAS) and hypertension. The study analyzed clinical data from a total of 840 OSAS patients at Wuhan Union Hospital between January 2020 to December 2023. The association between TyG-BMI and hypertension was examined using restricted cubic spline regression and logistic regression. Mediation effect analysis was conducted to explore the relationship between OSAS, TyG-BMI, and the risk of hypertension. Severe OSAS was associated with a significantly increased risk of hypertension compared to mild OSAS (OR = 1.752, p = 0.013). There was a positive linear relationship between TyG-BMI and the risk of hypertension (P-non-linear = 0.535). The risk of hypertension increased with increasing TyG-BMI, with a significantly higher risk of hypertension in the fourth quartile (OR = 3.407, p

Abstract UVB radiation induces oxidative stress, DNA damage, and inflammation, leading to skin wrinkling, compromised barrier function, and an increased risk of carcinogenesis. Addressing or preventing photoaging may offer a promising therapeutic avenue for these conditions. Recent research indicated that mesenchymal stem cells (MSCs) exhibit significant therapeutic potential for various skin diseases. Given that extracellular vesicles (EV) can deliver diverse cargo to recipient cells and elicit similar therapeutic effects, we investigated the roles and underlying mechanisms of both adipose-derived MSC-derived EV (AMSC-EV) and umbilical cord-derived MSC-derived EV (HUMSC-EV) in photoaging. Our findings indicated that in vivo, treatment with AMSC-EV and HUMSC-EV resulted in improvements in wrinkles and skin hydration while also mitigating skin inflammation and thickness alterations in both the epidermis and dermis. Additionally, in vitro studies using human keratinocytes (HaCaTs), human dermal fibroblast cells (HDFs), and T-Skin models revealed that AMSC-EV and HUMSC-EV attenuated senescence, reduced levels of reactive oxygen species (ROS) and DNA damage, and alleviated inflammation induced by UVB. Furthermore, EV treatment enhanced cell viability and migration capacity in the epidermis and promoted extracellular matrix (ECM) remodeling in the dermis in photoaged cell models. Mechanistically, proteomics results showed that TIMP1 was highly expressed in both AMSC-EV and HUMSC-EV and could exert similar effects as MSC-EV. In addition, we found that EV and TIMP1 could inhibit Notch1 and downstream targets Hes1, P16, P21, and P53. Collectively, our data suggests that both AMSC-EV and HUMSC-EV attenuate skin photoaging through TIMP1/Notch1.

Abstract The major crop, soybean, forms root nodules with symbiotic rhizobia, providing energy and carbon to the bacteria in exchange for bioavailable nitrogen. The relationship is host-specific and highly host-regulated to maximize energy efficiency. Symbiotic nitrogen fixation (SNF) is greener than synthetic fertilizer for replenishing soil fertility, contributing to yield increase. Nodulation Outer Protein P (NopP) and NopI of the type 3 secretion system (T3SS) of the rhizobium determine host specificity. Sinorhizobium fredii CCBAU25509 (R2) and CCBAU45436 (R4) have different NopP and NopI variants, affecting their respective symbiotic compatibilities with the cultivated soybean C08 and the wild soybean W05. Swapping the NopP variants between R2 and R4 has been shown to switch their compatibility with C08 with the rj2/Rfg1 genotype. To understand the effects of Nops on host compatibility, analyses on the transcriptomic data of W05 roots and nodules inoculated with S. fredii strains containing Nop variants uncovered many differentially expressed genes related to nodulation and nodule functions, providing important information on the effects of Nops on hosts and nodules.

Abstract This article delves into a hybrid galloping energy harvester featuring a longitudinally aligned triangular-shaped bluff body. Numerically, it analyzes how the position of a lumped mass influences the average output power of the harvester under concurrent base excitation and galloping. In comparison with traditional hybrid energy harvesters, the impact of three factors—low airflow velocity, small base excitation amplitude, and low frequency—is examined for each case of lumped mass deployment. The findings reveal that optimal mass positioning markedly enhances the harvester’s average power output when there are low airflow velocities, small base excitation amplitudes, and low frequencies, constituting a novel contribution to the field. Through numerous numerical simulations, it is determined that the optimal position for deploying the lumped mass is approximately 60–70% along the length of the cantilever beam substrate.

Abstract This study aimed to evaluate the correlation between mental health status and arterial stiffness. A Symptom Checklist 90 (SCL-90) score was conducted for 10,688 employees of Kailuan Group Co., Ltd., of which 4936 participants received baPWV measurement. Of these, 4424 met the inclusion criteria. Based on the SCL-90 score, the study subjects were divided into normal mental health group (SCL-90 score

Abstract Background Apocrine carcinoma associated with Paget’s disease is a rare malignancy that typically manifests in elderly individuals, predominantly affecting the geriatric population. It commonly arises in regions rich in apocrine glands and often exhibits an insidious onset, potentially requiring several years to be diagnosed. Case presentation An 80-year-old male was simultaneously diagnosed with scrotal apocrine carcinoma (showing Paget changes) and early-stage gastric cancer. Whole-genome exome sequencing confirmed these as independent malignancies with minimal genetic overlap, indicating that they were two primary tumors. The patient initially underwent successful surgery but experienced recurrence and metastasis. Treatment with capecitabine and paclitaxel showed promising responses, highlighting similarities between breast and apocrine carcinomas. Challenges were noted in the use of genetic testing and drug susceptibility assessments for treatment guidance. Notably, HER-2 expression in metastatic lesions, a trait of apocrine carcinoma, has remained unexplored due to negative HER-2 FISH results and a lack of available targeted therapies in China. Conclusion Elderly patients often exhibit a lesser degree of aggressiveness toward treatment following a diagnosis of malignant tumors. It is imperative to carefully consider how to strike a balance between effective treatment and maintaining a satisfactory quality of life for these patients. This case underscores the complexity of treating coexisting rare cancers in older adults and emphasizes the need for personalized treatments and continued innovation in cancer therapy. The insights gained offer significant value in understanding and managing such rare cancer cases.

Objectives: This study explores the correlation between serum cholesterol, interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and post-intracerebral hemorrhage (post-ICH) depression in patients with acute ICH. Methods: 35 patients with acute primary supratentorial ICH were recruited. Serum cholesterol, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDLC), IL-10, and MIF were measured in the first morning after admission. Additionally, a 24-item Hamilton Depression Scale (HAMD-24) was used to detect depressive symptoms one week after admission. HAMD scores ≥ 8 indicated a diagnosis of post-ICH depression. Results: The levels of TC were significantly lower in ICH patients with depression compared to those without [169.26(139.23–215.67) mg/dL vs. 200.46(182.81–224.74) mg/dL, P = 0.010]. Similarly, levels of LDLC [102.18(78.39–137.28) mg/dL vs. 135.14(120.22–170.63) mg/dL, P = 0.001] and IL-10 [17.56(16.03–22.52) pg/mL vs. 31.17(23.42–37.53) pg/mL, P = 0.001] were also lower in patients with post-ICH depression. Furthermore, the levels of TC (r = -0.433, P = 0.009), TG (r = -0.345, P = 0.043), LDLC (r = -0.549, P = 0.001), and IL-10 levels (r = -0.603, P

Abstract Background Cancer patients’ health-related quality of life (HRQoL) has always been a hot discussion spot. Loneliness and psychological resilience are considered to be significant psychosocial factors impacting the HRQoL of the cancer population. However, there is a lack of studies on the interrelationship among loneliness, resilience, and HRQoL in patients with nasopharyngeal carcinoma (NPC). This study aims to explore the relationship between resilience and HRQoL among NPC patients and to recognize the potential mediating role of loneliness in this relationship. Methods A cross-sectional study was performed in this study. A convenience sampling method was conducted to recruit participants. A total of 155 patients with nasopharyngeal carcinoma were required to complete the socio-demographic questionnaire, the Cancer Loneliness Scale (CLS), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the European Organization for Research and Treatment of Quality of Life Questionnaire C-30 (EORTC QLQ-C30) from April 2022 to August 2022 in a tertiary grade A hospital in Guangzhou, China. The multiple linear regression analysis was used to identify influencing factors, and structural equation modeling with the bootstrap method was performed to test the mediating role of loneliness. This study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Results HRQoL was at a median level among NPC patients, with a mean score of 64.19 (24.38) on the Global health status/quality of life (GHS/QoL) scale. Monthly household income (B = 4.973, P

Abstract Background Myelocytomatosis (MYC) transcription factors are crucial mediators of the response of plants to environmental stresses through via binding to DNA regulatory regions. However, few systematic characterizations of MYC genes are available in Cucurbitaceae species. Results In this study, we identified 10, 8, 12, and 10 MYC genes in Cucumis sativus, Cucumis melo, Citrullus lanatus, and Benincasa hispida, respectively. Characterization revealed that all of the MYC proteins contain a highly conserved H4-V5-E6-E8-R9-R11-R12 sequence, which is essential for the binding of DNA regulatory regions. Evolutionary analysis enabled us to categorize 40 predicted MYC proteins from seven species into five distinct groups and revealed that the expansion of the MYC genes occurred before the divergence of monocots and dicots. The upstream promoter regions of the MYC genes contain a variety of developmental, stress, and hormone-responsive regulatory elements. The expression of cucumber MYC genes varies significantly across organs, with particularly high expression of CsaV3_3G001710 observed across all organs. Transcriptomic analysis revealed that certain cucumber MYC genes undergo specific upregulation or downregulation in response to both biotic and abiotic stressors. In particular, under temperature stress, the cucumber genes CsaV3_3G007980 and CsaV3_3G001710 were significantly upregulated. Interestingly, the homologs of these two genes in C. lanatus presented a similar expression pattern to that in C. sativus, whereas in B. hispida, they presented the opposite pattern, i.e., significant downregulation. These findings indicated that these two genes indeed respond to temperature stress but with different expression patterns, highlighting the divergent functions of homologous genes across different species. Conclusions This study analyzed the size and composition of the MYC gene family in four Cucurbitaceae species and investigated stress-responsive expression profiles, especially under temperature stress. All the results showed that MYC genes play important roles in development and stress responses, laying a theoretical foundation for further investigations of these response mechanisms.

Abstract Evidence for the treatment of patients with mild-to-moderate chronic obstructive pulmonary disease (COPD) is limited. The efficacy of N-acetylcysteine (an antioxidant and mucolytic agent) for patients with mild-to-moderate COPD is uncertain. In this multicentre, randomised, double-blind, placebo-controlled trial, we randomly assigned 968 patients with mild-to-moderate COPD to treatment with N-acetylcysteine (600 mg, twice daily) or matched placebo for two years. Eligible participants were 40-80 years of age and had mild-to-moderate COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity ratio

Abstract Mobile genetic elements (MGEs) enable bacteria to acquire novel genes and traits. However, the functions of cargo genes within MGEs remain poorly understood. The cadmium resistance operon cadDX is present in many gram-positive bacteria. Although cadDX has been reported to be involved in metal detoxification, its regulatory mechanisms and functions in bacterial pathogenesis are poorly understood. This study revealed that cadDX contributes to cadmium resistance, oxidative stress resistance, and virulence in Streptococcus suis, an important zoonotic pathogen in pigs and humans. CadX represses cadD expression by binding to the cadDX promoter. Notably, cadX responds to H2O2 stress through an additional promoter within the cadDX operon, mitigating the harmful effect of excessive cadD expression during oxidative stress. cadDX resides within an 11 K integrative and mobilizable element that can autonomously form circular structures. Moreover, cadDX is found in diverse MGEs, accounting for its widespread distribution across various bacteria, especially among pathogenic streptococci. Transferring cadDX into another zoonotic pathogen, Streptococcus agalactiae, results in similar phenotypes, including resistance to cadmium and oxidative stresses and increased virulence of S. agalactiae in mice. The new functions and regulatory mechanisms of cadDX shed light on the importance of the cadDX system in driving evolutionary adaptations and survival strategies across diverse gram-positive bacteria.

High-performance grinding wheels are critical tools for precision surface generation. In precision grinding processes, the coolant supply at the wheel-workpiece interface is critical for reducing grinding temperature and detrimental friction. For better lubrication and chip removal performance, the cavities or pores need to be generated throughout the grinding wheel. The ideal morphology of pores in grinding wheels should be inter-connected and capable of providing sufficient coolant. Conventional grinding wheel design and fabrication methods can only passively generate closed circular pores by using pore-forming agents. Increasing the percentage of pores in this way generally leads to an uncontrollable reduction in mechanical strength, while the closed pores are insufficient in cooling performance. In this paper, the grinding wheels with triply periodic minimal surface lattice structure are designed and fabricated, which achieves the regulable and inter-connected internal structure of grinding wheels. Meanwhile, to balance the relationship between the structural properties and performance indicators of porous grinding wheels, an optimal design method for the porous structure of grinding wheels is proposed. Finally, the grinding performance of the novel grinding wheels in comparison to electroplated diamond grinding wheels is investigated in terms of grinding force, specific grinding energy and ground surface roughness.

Abstract The neighborhood effect has become an important framework with which to study the mechanisms that maintain the coexistence of tree species. Phylogenetic relatedness among neighboring plants directly affects species coexistence and the maintenance of tree diversity. And some studies have reported that seedling performance is negatively correlated with phylogenetic relatedness, which termed phylogenetic negative density dependence. Soil-borne fungal pathogens affected seedling performance of phylogenetically related host species, i.e., phylogenetic Janzen–Connell effect. Seedlings may be particularly vulnerable to habitat and neighbor characteristics. Although previous studies have demonstrated the influence of neighborhood effects, phylogenetic relatedness, and habitat filtering on seedling survival, growth, and mortality, the effect of variation in these factors on seedling abundance remains unclear. To address this question, we used a 4-ha (200 m × 200 m) and monitored four-year (2020–2023) seedling dataset from a mid-montane humid evergreen broad-leaved subtropical forest in the Gaoligong Mountains, Yunnan, Southwestern China, and which consisted of 916 seedlings belonging to 56 species. The results of generalized linear mixed models showed no significant effect of conspecific adult neighbors on seedling abundance at any of the intervals evaluated. In contrast, we found evidence of phylogenetic distance density dependence in the forests of the Gaoligong Mountains. Specifically, there was a significant positive effect of the relative average phylogenetic distance between heterospecific adult neighbors and focal seedlings on focal seedling abundance in 2020; however, the relative average phylogenetic distance between heterospecific seedling neighbors and focal seedlings had a significant negative effect on seedling abundance over the four-year period (2020–2023). Among the habitat factors, only light (canopy opening) had a negative effect on seedling abundance in all four years. Light resources may be a limiting factor for seedlings, and determine seedling dynamics in subtropical forests. Overall, our results demonstrated that phylogenetic density dependence and habitat filtering affected subtropical seedling abundance. Our findings provide new evidence of the impact of phylogenetic density dependence on seedling abundance in a subtropical mid-montane humid evergreen broad-leaved forest and highlight the need to incorporate the neighborhood effect, phylogenetic relatedness, and habitat factors in models assessing seedling abundance.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Objective To investigate the serological characteristics and gene mutation mechanism of RhD variant blood donors in Zhengzhou. Methods From January 2023 to December 2023, 1 619 RhD-negative blood donors sent to our laboratory were selected for the study, and RhD negative confirmation test and RhCE phenotype detection were applied by tube method and microcolumn gel indirect antiglobulin test method. RHD gene amplification and Sanger sequencing were used to detect RhD variant sample genotypes. Results A total of 69 cases of RhD variants were detected in the RhD negative confirmation test, with a proportion of 4.26%(69/1 619).The RhCE phenotypes were ccEe, Ccee, CcEe and CCee.There were 17 genotypes and 15 phenotypes of the D variant.The RHD*weak partial 15 allele was the most frequent(33 cases), with a frequency of 47.83%(33/69), and the main phenotype was the ccEe. This was followed by the RHD*DVI.3 allele in 20 cases with a frequency of 28.99%(20/69) and the predominant phenotype was Ccee. The RHD*weak partial 15/RHD*01EL.01 heterozygote was found in 3 cases with a frequency of 4.35%(3/69), all with the CcEe phenotype. Other rare genotypes were present in 13 cases with a frequency of 18.84%(13/69). Antibody screening was positive in 3 cases with a frequency of 4.35%(3/69). Two cases of female blood donors, both with history of pregnancy and childbirth, were identified as anti-D; one case of male donor was anti-M. Conclusion The RHD*weak partial 15 genotype was the most common among the RhD variants in blood donors in Zhengzhou, followed by the RHD*DVI.3 genotype. It plays an important role in guaranteeing the safety of blood supply and guiding precision transfusion.

A suitable irrigation pattern is of great significance for reducing greenhouse gas emissions. In this study, field experiments and a denitrification-decomposition (DNDC) model were used to study the global warming potential based on CH4, N2O and CO2 fluxes under flooding irrigation and controlled irrigation in paddy fields in the Erhai Lake basin. The results showed that the average value of CH4 flux under controlled irrigation was lower than that under flooding irrigation, with a reduction range of 43.21% to 48.88%, however, the average value of the N2O and CO2 fluxes from paddy field under controlled irrigation were higher than those under flooding irrigation. Controlled irrigation patterns can significantly reduce the global warming potential in paddy fields based on CH4, N2O and CO2 fluxes. Controlled irrigation can effectively reduce the global warming potential per unit yield. For water management in the Erhai Lake basin, it is recommended the controlled irrigation treatment of soil moisture with an upper limit of 100% and a lower limit of 75-85% with irrigation, and a maximum surface water depth of 150-200 mm lasting for five days after precipitation from the jointing-booting stage to the milk stage.

The effect of germination degree (shoot length) on the content of nutritional and bioactive components, antioxidant activity was investigated in tartary buckwheat whole grain powder (TBWGP). The findings demonstrated that as germination degree increased, the absolute contents of total starch, protein and fat fractions as well as the ratio of straight-chain starch to total starch in TBWGP decreased, and the content of dietary fiber (IDF, SDF, TDF) elevated (P

Abstract Background This study is to propose a clinically applicable 2-echelon (2e) diagnostic criteria for the analysis of thyroid nodules such that low-risk nodules are screened off while only suspicious or indeterminate ones are further examined by histopathology, and to explore whether artificial intelligence (AI) can provide precise assistance for clinical decision-making in the real-world prospective scenario. Methods In this prospective study, we enrolled 1036 patients with a total of 2296 thyroid nodules from three medical centers. The diagnostic performance of the AI system, radiologists with different levels of experience, and AI-assisted radiologists with different levels of experience in diagnosing thyroid nodules were evaluated against our proposed 2e diagnostic criteria, with the first being an arbitration committee consisting of 3 senior specialists and the second being cyto- or histopathology. Results According to the 2e diagnostic criteria, 1543 nodules were classified by the arbitration committee, and the benign and malignant nature of 753 nodules was determined by pathological examinations. Taking pathological results as the evaluation standard, the sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) of the AI systems were 0.826, 0.815, 0.821, and 0.821. For those cases where diagnosis by the Arbitration Committee were taken as the evaluation standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.946, 0.966, 0.964, and 0.956. Taking the global 2e diagnostic criteria as the gold standard, the sensitivity, specificity, accuracy, and AUC of the AI system were 0.868, 0.934, 0.917, and 0.901, respectively. Under different criteria, AI was comparable to the diagnostic performance of senior radiologists and outperformed junior radiologists (all P 0.05). Conclusions The proposed 2e diagnostic criteria are consistent with real-world clinical evaluations and affirm the applicability of the AI system. Under the 2e criteria, the diagnostic performance of the AI system is comparable to that of senior radiologists and significantly improves the diagnostic capabilities of junior radiologists. This has the potential to reduce unnecessary invasive diagnostic procedures in real-world clinical practice.

Abstract The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.

Abstract Biological ion channels exhibit high selectivity and permeability of ions because of their asymmetrical pore structures and surface chemistries. Here, we demonstrate a biomimetic nanofluidic channel (BNC) with an asymmetrical structure and glycyl-L-proline (GLP) -functionalization for ultrafast, selective, and unidirectional Dy3+ extraction over other lanthanide (Ln3+) ions with very similar electronic configurations. The selective extraction mainly depends on the amplified chemical affinity differences between the Ln3+ ions and GLPs in nanoconfinement. In particular, the conductivities of Ln3+ ions across the BNC even reach up to two orders of magnitude higher than in a bulk solution, and a high Dy3+/Nd3+ selectivity of approximately 60 could be achieved. The designed BNC can effectively extract Dy3+ ions with ultralow concentrations and thereby purify Nd3+ ions to an ultimate content of 99.8 wt.%, which contribute to the recycling of rare earth resources and environmental protection. Theoretical simulations reveal that the BNC preferentially binds to Dy3+ ion due to its highest affinity among Ln3+ ions in nanoconfinement, which attributes to the coupling of ion radius and coordination matching. These findings suggest that BNC-based ion selectivity system provides alternative routes to achieving highly efficient lanthanide separation.

In order to study the effects of reverse transcriptase inhibitors, protease inhibitors and flavonoids on two target cells infected by HIV in a heterogeneous environment, an HIV mathematical model at the cellular level was established. Research shows that infected cells can be categorized into immature infected cells, latent infected cells, and mature infected cells based on the infection process. The basic reproduction number $ R_{0} $ was established, and it is proved that $ R_{0} $ serves as a threshold parameter: When $ R_{0} < 1 $, the disease-free steady state is globally asymptotically stable, and the disease is extinct; when $ R_{0} > 1 $, the solution of the system is uniformly persistent, and the virus exists. Considering the huge advantages of drug intervention in controlling HIV infection, the optimal control problem was proposed under the condition that the constant diffusion coefficient is positive, so as to minimize the total number of HIV-infected cells and the cost of drug treatment. To illustrate our theoretical results, we performed numerical simulations in which the model parameters were obtained with reference to some medical studies. The results showed that: (1) as $ R_{0} $ increases, the risk of HIV transmission increases; (2) pharmacological interventions are important in early treatment of HIV spread and control of viral load in the body; (3) the treatment process must consider the heterogeneity of medication, otherwise it will not be conducive to suppressing the spread of the virus and will increase costs.

Objective To analyze the application of serological test results in the diagnosis and treatment of anti-M-induced hemolytic disease of the fetus and newborn(HDFN), and to explore HDFN prevention strategies. Methods The serological test results of 12 cases of HDFN caused by anti-M diagnosed in our laboratory from January 2017 to December 2023 were retrospectively analyzed, including blood group identification of mothers and children, serum total bilirubin/hemoglobin/antibody titer test, and three hemolysis tests in newborns. Clinical data of the children and mothers were collected, including pregnancy history, blood transfusion history, prenatal antibody testing, history of intrauterine blood transfusion and gestational week of delivery, and the prognosis of the children was followed up. Results All 12 cases of fetal neonatal hemolytic disease due to anti-M were RhD+ MN phenotype newborn born to RhD+ NN mother, with maternal- fetal incompatiblility in MN blood groups. In the ABO blood group system, ABO incompatibility between mother and child accounted for 41.7%(5/12).None of the mothers had a history of blood transfusion, and the median titer of the test at 4℃ was 32, and the median titer at 37℃ was 4. The mothers of 3 cases had a history of multiple intrauterine blood transfusions, with an incidence of 25%(3/12). One case had an abnormal first pregnancy, with an incidence of 8.3%(1/12), and seven cases had an abnormal pregnancy with a miscarriage, with an incidence of abnormal pregnancy and birth history of 58.3%(7/12). There were 6 cases of premature labor, with an incidence of 50%(6/12). The mothers in three cases underwent regular obstetric examination and the specificity of the antibodies was determined, accounting for 25%(3/12). Twelve children had free antibodies with a median titer of 6 at 4℃ and 2 at 37℃. Two children had anti-M antibodies that were not reactive at 37℃, with a negative rate of 16.7%(2/12). The positive rate of DAT and elution test was respectively 8.3%(1/12) and 16.7%(2/12) in the children. The median minimum hemoglobin value was 75 g/L, and all 12 children received blood transfusions. The median peak total bilirubin value was 157.5 μmol/L, and none of them reached the threshold for blood exchange. The rate of delayed anemia was 16.7%(2/12), the postnatal mortality rate was 8.3%(1/12), and 11 children was free of growth and neurodevelopmental delay in prognosis. Conclusion Anti-M can cause severe HDFN, which can also occur in primigravida. The intensity of antibody titer does not correlate with the severity of the disease, and it is prone to cause delayed anemia, which should be monitored regularly according to the serological characteristics of anti-M and clinical symptoms, and should be treated timely.

Abstract Background Malignant pleural effusion (MPE) is frequently observed in patients with advanced lung adenocarcinoma (LUAD). Pleural fluid cytology is a less invasive procedure compared to pleural biopsy. Therefore, it is crucial to identify novel effective biomarkers for LUAD-associated pleural fluid cytology. Methods The RNA sequencing (RNA-Seq) and clinical data of LUAD cases were downloaded from TCGA and OncoSG databases. Differential gene expression analysis, survival analysis and immune cell infiltration analysis were performed on the LUAD datasets. The expression levels of FAM83A, TFF-1, and NapsinA in 94 paired LUAD and adjacent normal tissues, and in the pleural effusion specimens of 40 LUAD and 21 non-neoplastic patients were evaluated by immunohistochemistry. Results FAM83A expression levels were significantly different between the LUAD and normal tissue datasets, and correlated with overall or disease-free survival, and histological grade of the tumors. Furthermore, the in-situ expression of FAM83A was higher in 89/94 LUAD tissues compared to the paired normal tissues. FAM83A expression was significantly correlated with immune cell infiltration, and showed a positive association with macrophage infiltration. In addition, FAM83A staining was positive in 37 LUAD pleural effusion samples, and negative in 20 non-neoplastic pleural effusion samples. The expression pattern of FAM83A in the pleural effusion of LUAD patients was relatively consistent with that of TFF-1 and NapsinA, and even stronger in some specimens that were weakly positive or negative for TTF1/NapsinA. Conclusions FAM83A is a promising immune-related biomarker in LUAD biopsy specimens and pleural fluid, and can distinguish between malignant and benign pleural effusion.

Abstract Migratory birds are important vectors for virus transmission, how migratory birds recognize viruses and viruses are sustained in birds is still enigmatic. As an animal model for waterfowl among migratory birds, studying and dissecting the antiviral immunity and viral evasion in duck cells may pave a path to deciphering these puzzles. Here, we studied the mechanism of antiviral autophagy mediated by duck STING in DEF cells. The results collaborated that duck STING could significantly enhance LC3B-II/I turnover, LC3B-EGFP puncta formation, and mCherry/EGFP ratio, indicating that duck STING could induce autophagy. The autophagy induced by duck STING is not affected by shRNA knockdown of ATG5 expression, deletion of the C-terminal tail of STING, or TBK1 inhibitor BX795 treatment, indicating that duck STING activated non-classical selective autophagy is independent of interaction with TBK1, TBK1 phosphorylation, and interferon (IFN) signaling. The STING R235A mutant and Sar1A/B kinase mutant abolished duck STING induced autophagy, suggesting binding with cGAMP and COPII complex mediated transport are the critical prerequisite. Duck STING interacted with LC3B through LIR motifs to induce autophagy, the LIR 4/7 motif mutants of duck STING abolished the interaction with LC3B, and neither activated autophagy nor IFN expression, indicating that duck STING associates with LC3B directed autophagy and dictated innate immunity activation. Finally, we found that duck STING mediated autophagy significantly inhibited duck plague virus (DPV) infection via ubiquitously degraded viral proteins. Our study may shed light on one scenario about the control and evasion of diseases transmitted by migratory birds.

This is an article in the field of mining engineering. Fly ash is not only a large amount of solid waste discharged from coal-fired power plants, but also a potential secondary resource. At present, although the resource utilization of fly ash covers a wide range of fields, the high value utilization rate is low. The main chemical components of fly ash are silicon and alumina. Making full use of aluminum and silicon resources is one of the important ways to improve its resource utilization. In this article, the application of fly ash in the extraction of metallurgical grade alumina, preparation of non-metallurgical grade alumina, silica, silica aerogels, silicon-aluminum composites and other high value-added products are reviewed. The existing problems of high value utilization are analyzed and the future development trend is pointed out.

Abstract Background Glioblastoma (GBM) is a highly heterogeneous, recurrent and aggressively invasive primary malignant brain tumor. The heterogeneity of GBM results in poor targeted therapy. Therefore, the aim of this study is to depict the cellular landscape of GBM and its peritumor from a single-cell perspective. Discovering new cell subtypes and biomarkers, and providing a theoretical basis for precision therapy. Methods We collected 8 tissue samples from 4 GBM patients to perform 10 × single-cell transcriptome sequencing. Quality control and filtering of data by Seurat package for clustering. Inferring copy number variations to identify malignant cells via the infercnv package. Functional enrichment analysis was performed by GSVA and clusterProfiler packages. STRING database and Cytoscape software were used to construct protein interaction networks. Inferring transcription factors by pySCENIC. Building cell differentiation trajectories via the monocle package. To infer intercellular communication networks by CellPhoneDB software. Results We observed that the tumor microenvironment (TME) varies among different locations and different GBM patients. We identified a proliferative cluster of oligodendrocytes with high expression of mitochondrial genes. We also identified two clusters of myeloid cells, one primarily located in the peritumor exhibiting an M1 phenotype with elevated TNFAIP8L3 expression, and another in the tumor and peritumor showing a proliferative tendency towards an M2 phenotype with increased DTL expression. We identified XIST, KCNH7, SYT1 and DIAPH3 as potential factors associated with the proliferation of malignant cells in GBM. Conclusions These biomarkers and cell clusters we discovered may serve as targets for treatment. Targeted drugs developed against these biomarkers and cell clusters may enhance treatment efficacy, optimize immune therapy strategies, and improve the response rates of GBM patients to immunotherapy. Our findings provide a theoretical basis for the development of individualized treatment and precision medicine for GBM, which may be used to improve the survival of GBM patients.

Background First‐pass successful reperfusion (FPSR), defined as a successful/complete reperfusion achieved after a single thrombectomy pass, is predictive of favorable outcome in patients with acute ischemic stroke with large‐vessel occlusion. It is unknown whether intravenous tirofiban is effective in increasing the rate of FPSR in acute anterior large‐vessel occlusion stroke. Methods and Results Patients who had acute large‐vessel occlusion stroke presenting within 24 hours and underwent endovascular thrombectomy were analyzed from the RESCUE BT (Intravenous Tirofiban for Patients With Large Vessel Occlusion Stroke) clinical trial, of which the main analysis was neutral. The RESCUE BT trial randomized patients to receive either intravenous tirofiban or placebo before endovascular thrombectomy. The primary end point was FPSR, defined as successful reperfusion (extended thrombolysis in cerebral infarction scale 2b50, 2c, or 3) at first thrombectomy attempt. A modified Poisson regression analysis assessed the association between intravenous tirofiban treatment and FPSR. Of 948 enrolled patients, 463 patients were randomized to the tirofiban group and 485 to the placebo group. The mean age was 67 years, and 41.0% of the patients were women. FPSR was achieved more often in the tirofiban group (30.5% versus 23.5%; adjusted risk ratio, 1.24 [95% CI, 1.01–1.51]; P=0.04). FPSR was associated with a favorable shift to lower modified Rankin Scale disability levels at 90 days (common odds ratio, 1.42 [95% CI, 1.08–1.86]; P=0.01). Conclusions In this post hoc analysis of the RESCUE BT trial, treatment with intravenous tirofiban before endovascular thrombectomy was associated with increased FPSR in patients with acute ischemic stroke due to large‐vessel occlusion in the anterior circulation. FPSR was associated with reduced 90‐day levels of disability. Registration URL: http://chictr.org; Unique Identifier: ChiCTR‐INR‐17014167.

This case describes a patient with anaphylaxis caused by traditional Chinese medicine. Skin prick test with the traditional Chinese medicine decoction indicates that he was allergic to Suan Zao Ren. The patient had pollinosis and had never taken Suan Zao Ren before, thus we need to think the possibility of pollen food allergy syndrome. This paper also proposes a procedure for doctors to identify the specific culprit of traditional Chinese medicine decoction.

BackgroundBy using meta-analysis to evaluate the effects of exercise on adolescent body mass index (BMI), standing long jump, sit ups, lung capacity, sitting forward bending, 50 m running, and 800 m running, a large amount of literature will be reviewed to reveal the key role of exercise in the healthy development of adolescents. This study aims to promote the development of adolescent physical health and solve the common problem of declining physical fitness, comprehensively improve the physical fitness of adolescents, and provide decision-making support for policymakers. The research results will provide methodological references for precise and effective intervention practices, further improve adolescent physical fitness, and lay a solid physiological foundation for their comprehensive development.MethodsA literature search was conducted on China National Knowledge Infrastructure (CNKI) and PubMed, collecting randomized controlled trials (RCTs) that investigated the effects of physical activity on adolescent physical fitness according to predefined criteria. The quality of these studies was assessed, and their outcome data were analyzed using RevMan 5.4 software. The analysis encompassed 13 articles with a total of 4,633 participants, examining measures such as mean difference (MD) and heterogeneity, followed by subgroup analyses.ResultsThe meta-analysis revealed that physical activity had a moderate to high effect on adolescent performance in sit-ups (MD = 4.91, 95% CI = 3.41–6.41), vital capacity (MD = 120.66, 95% CI = 48.67–194.46), sit-and-reach test (MD = 0.82, 95% CI = 0.09–1.56), 50-meter dash (MD = −1.05, 95% CI = −1.48 to −0.62), and 800-meter run (MD = −18.48, 95% CI = −24.98 to −11.97). Conversely, its influence on BMI (MD = −0.31, 95% CI = −1.87 to 1.24) and standing long jump (MD = 0.1, 95% CI = 0.05–0.15) was relatively low.ConclusionEngaging in physical activities significantly improves adolescent physical fitness. The most effective regimen involves a combination of aerobic and anaerobic exercises, with each session lasting 30 min, performed three times per week for at least 2 months. The extent of improvement in various fitness indicators, reflecting different aspects of physical fitness, is influenced by factors such as the nature of the physical activity, intervention duration, exercise frequency, and age.Systematic Review RegistrationPROSPERO, identifier CRD42024568197

BackgroundRecurrent pregnancy loss (RPL) affects women's reproductive health seriously, with immune dysfunction playing a key role in its cause, yet the exact mechanisms remain elusive. We aim to investigate potential mechanisms and identify biomarkers linked to RPL.MethodsImmune cytokine testing and metabolomic profiling were conducted on the serum of 34 RPL patients and 30 healthy individuals. The metabolic pathways of the differential metabolites were analyzed, and specific metabolites were validated through targeted profiling. Potential biomarkers were identified, and the relationships between immune cytokines and differential metabolites were explored.ResultsIn the RPL group, serum interleukin-6 and interleukin-10 levels were significantly higher, while interleukin-2 and interferon-γ were significantly lower. A total of 296 differential metabolites were detected by untargeted metabolomic profiling between the RPL and control groups, with most linked to amino acid metabolism. Targeted metabolomic profiling of amino acid metabolism revealed upregulation of indole-3-acetic acid, tyrosine, glycine, isoleucine, tryptophan, lysine, aspartic acid, arginine, leucine, threonine, glutamic acid, cystine, and phenylpyruvic acid (PPA) in the RPL group. Moreover, PPA and 5-hydroxy-L-tryptophan showed great potential in predicting RPL in a diagnostic model. Cystine and tyrosine were associated with immune cytokines in correlation analysis.ConclusionThe study highlights the role of amino acid metabolism in RPL pathogenesis, suggesting that PPA and 5-HTP may be potential predictive indicators, while cystine and tyrosine may potentially regulate immune responses related to RPL. Further investigation into the molecular mechanisms underlying these findings could potentially result in the creation of novel diagnostic and therapeutic approaches for RPL.

Summary: Hypervirulent Klebsiella pneumoniae (hvKp) is a significant causative agent of invasive hepatic abscess syndrome in Asia, presenting substantial clinical challenges due to its intricate pathogenesis. This study revealed the crucial role of the gut microbiota in fortifying the host’s defense against hvKp infection by enhancing interleukin-22 (IL-22), probably through regulating downstream antimicrobial peptides such as Reg3β. In antibiotic-treated mice, we observed that gut microbiota disruption impaired the transformation of tryptophan to indole, a key ligand for the aryl hydrocarbon receptor (AhR), consequently affecting the regulatory functions of IL-22. Our experimental findings revealed that administering rIL-22 or indole propionic acid notably diminished the translocation of hvKp from the intestine to the liver. This research not only underscores the pivotal role of the gut microbiome in modulating tryptophan metabolism and the IL-22 pathway but also highlights its critical function in preventing hvKp migration from the colon to the liver.

Arsenic (As) is a widespread global pollutant, and there is significant controversy surrounding its complex relationship with obesity, primarily focused on short-term exposure. Recognizing the prolonged nature of dietary arsenic exposure, this study involved feeding mice with arsenic-contained food for 14 months. The results showed that mice exposed to arsenic developed a non-alcoholic fatty liver condition, characterized by a light-yellow hue on the liver surface and various pathological alterations in the liver cells, including enlarged nuclei, cellular necrosis, inflammatory infiltration, dysfunctional mitochondria, and endoplasmic reticulum disorganization. There were also disruptions in biochemistry indices, with a significant increase in total cholesterol (TC) level and a decrease in high-density lipoprotein (HDL) level. However, some contradictory observations occurred, such as a significant decrease in body weight, triglyceride (TG) level, and the numbers of lipid droplets. Several genes related to lipid metabolism were tested, and a model was used to explain these discrepancies. Besides, examinations of the colon revealed compromised intestinal barrier function and signs of inflammation. Fecal 16S rRNA sequencing and pseudo-targeted metabolomics revealed disruptions in internal homeostasis, such as modules, nodes, connections, and lipid-related KEGG pathways. Fecal targeted metabolomics analyses of short-chain fatty acids (SCFAs) and bile acids (BAs) demonstrated a significant upregulation in three primary bile acids (CA, CDCA, TCDCA), four secondary bile acids (TUDCA, DCA, LCA, GUDCA), and total SCFAs level. Oxidative stress and inflammation were also evident. Additionally, based on correlation analysis and mediation analysis, it was assumed that changes in the microbiota (e.g., Dubosiella) can impact the liver metabolites (e.g., TGs) through alterations in fecal metabolites (e.g., LPCs). These findings provide a theoretical reference for the long-term effect of arsenic exposure on liver lipid metabolism.

The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.

Chronic predator stress (CPS) is an important and ecologically relevant tool for inducing anhedonia in animals, but the neural circuits underlying the associated neurobiological changes remain to be identified. Using cell-type-specific manipulations, we found that corticotropin-releasing hormone (CRH) neurons in the medial subthalamic nucleus (mSTN) enhance struggle behaviors in inescapable situations and lead to anhedonia, predominately through projections to the external globus pallidus (GPe). Recordings of in vivo neuronal activity revealed that CPS distorted mSTN-CRH neuronal responsivity to negative and positive stimuli, which may underlie CPS-induced behavioral despair and anhedonia. Furthermore, we discovered presynaptic inputs from the bed nucleus of the stria terminalis (BNST) to mSTN-CRH neurons projecting to the GPe that were enhanced following CPS, and these inputs may mediate such behaviors. This study identifies a neurocircuitry that co-regulates escape response and anhedonia in response to predator stress. This new understanding of the neural basis of defensive behavior in response to predator stress will likely benefit our understanding of neuropsychiatric diseases.

The loss of nitrogen in soil damages the environment. Clarifying the mechanism of ammonium nitrogen (NH4+-N) transport in soil and increasing the fixation of NH4+-N after N application are effective methods for improving N use efficiency. However, the main factors are not easily identified because of the complicated transport and retardation factors in different soils. This study employed machine learning (ML) to identify the main influencing factors that contribute to the retardation factor (Rf) of NH4+-N in soil. First, NH4+-N transport in the soil was investigated using column experiments and a transport model. The Rf (1.29 – 17.42) was calculated and used as a proxy for the efficacy of NH4+-N transport. Second, the physicochemical parameters of the soil were determined and screened using lasso and ridge regressions as inputs for the ML model. Third, six machine learning models were evaluated: Adaptive Boosting, Extreme Gradient Boosting (XGB), Random Forest, Gradient Boosting Regression, Multilayer Perceptron, and Support Vector Regression. The optimal ML model of the XGB model with a low mean absolute error (0.81), mean squared error (0.50), and high test r2 (0.97) was obtained by random sampling and five-fold cross-validation. Finally, SHapely Additive exPlanations, entropy-based feature importance, and permutation characteristic importance were used for global interpretation. The cation exchange capacity (CEC), total organic carbon (TOC), and Kaolin had the greatest effects on NH4+-N transport in the soil. The accumulated local effect offered a fundamental insight: When CEC > 6 cmol+ kg−1, and TOC > 40 g kg−1, the maximum resistance to NH4+-N transport within the soil was observed. This study provides a novel approach for predicting the impact of the soil environment on NH4+-N transport and guiding the establishment of an early-warning system of nutrient loss.

IntroductionHemorrhagic Fever with Renal Syndrome (HFRS) is the most commonly diagnosed zoonosis in Asia. Despite taking various preventive measures, HFRS remains prevalent across multiple regions in China. This study aims to investigate the impact of climatic and environmental factors on the prevalence of HFRS in Anhui Province, China, utilizing satellite and reanalysis data.MethodsWe collect monthly HFRS data from Anhui Province spanning 2005 to 2019 and integrated MODIS satellite datasets and ERA5 reanalysis data, including variables such as precipitation, temperature, humidity, solar radiation, aerosol optical depth (AOD), and Normalized Difference Vegetation Index (NDVI). Continuous wavelet transform, Spearman correlation analysis, and Poisson regression analysis are employed to assess the association between climatic and environmental factors and HFRS cases.ResultsOur findings reveal that HFRS cases predominantly occur during the spring and winter seasons, with the highest peak intensity observed in a 9-year cycle. Notably, the monthly average relative humidity exhibits a Spearman correlation coefficient of 0.404 at a 4-month lag, taking precedence over other contributing factors. Poisson regression analysis elucidates that NDVI at a 2-month lag, mean temperature (T) and solar radiation (SR) at a 4-month lag, precipitation (P), relative humidity (RH), and AOD at a 5-month lag exhibit the most robust explanatory power for HFRS occurrence. Moreover, the developed predictive model exhibiting commendable accuracy.DiscussionThis study provides key evidence for understanding how climatic and environmental factors influence the transmission of HFRS at the provincial scale. Insights from this research are critical for formulating effective preventive strategies and serving as a resource for HFRS prevention and control efforts.

Prokaryotes play a crucial role in marine ecosystem health and drive biogeochemical processes. The northern Ninety East Ridge (NER) of the Indian Ocean, a pivotal yet understudied area for these cycles, has been the focus of our study. We employed high-throughput 16S rRNA gene sequencing to analyze 35 water samples from five stations along the ridge, categorized into three depth- and dissolved oxygen-level-based groups. Our approach uncovered a clear stratification of microbial communities, with key bioindicators such as Prochlorococcus MIT9313, Sva0996 marine group, and Candidatus Actinomarina in the upper layer; Ketobacter, Pseudophaeobacter, Nitrospina, and SAR324 clade in the middle layer; and Methylobacterium-Methylorubrum, Sphingomonas, Sphingobium, and Erythrobacter in the deep layer. Methylobacterium-Methylorubrum emerged as the most abundant bacterial genus, while Nitrosopumilaceae predominated among archaeal communities. The spatial and depth-wise distribution patterns revealed that Ketobacter was unique to the northern NER, whereas Methylobacterium-Methylorubrum, UBA10353, SAR324 clade, SAR406, Sva0996_marine_group, Candidatus Actinomarina were ubiquitous across various marine regions, exhibiting niche differentiation at the OTU level. Environmental factors, especially dissolved oxygen (DO), silicate, nitrate, and salinity, significantly influence community structure. These findings not only reveal the novelty and adaptability of the microbial ecosystem in the northern NER but also contribute to the broader understanding of marine microbial diversity and its response to environmental heterogeneity.

Developmental defects of enamel are common due to genetic and environmental factors before and after birth. Cdc42, a Rho family small GTPase, regulates prenatal tooth development in mice. However, its role in postnatal tooth development, especially enamel formation, remains elusive. Here, we investigated Cdc42 functions in mouse enamel development and tooth repair after birth. Cdc42 showed highly dynamic temporospatial patterns in the developing incisors, with robust expression in ameloblast and odontoblast layers. Strikingly, epithelium-specific Cdc42 deletion resulted in enamel defects in incisors. Ameloblast differentiation was inhibited, and hypomineralization of enamel was observed upon epithelial Cdc42 deletion. Proteomic analysis showed that abnormal mitochondrial components, phosphotransferase activity, and ion channel regulator activity occurred in the Cdc42 mutant dental epithelium. Reactive oxygen species accumulation was detected in the mutant mice, suggesting that abnormal oxidative stress occurred after Cdc42 depletion. Moreover, Cdc42 mutant mice showed delayed tooth repair and generated less calcified enamel. Mitochondrial dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression, increased Atp5j2 levels, and reactive oxygen species overproduction in the mutant repair epithelium. Epithelium-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical loop. Aberrant Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth repair. These findings suggested that mitochondrial dysfunction, up-regulated oxidative stress, and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant incisors. Overall, Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

SUMMARY: The administration of drugs via the oral route is challenging due to the presence of physiologic barrier. BCRP, which can actively transport substrates from intra- to extracellular environment, has an important functional role in the composition of physiologic barrier. Therefore, overcoming BCRP efflux is a strategy to improve the absorption of substrate drugs. Curcumin is a natural feed additive for poultry health and production. However, it is unknown whether curcumin affects the expression of BCRP. The purpose of this study was to investigate the role of curcumin in the regulation of BCRP and its influences on pharmacokinetics of BCRP substrate florfenicol. Results showed that curcumin (60 μM) inhibited the expression of BCRP mRNA by 58% and BCRP protein by 52% in primary chicken hepatocytes. Moreover, intracellular mitoxantrone (a selective BCRP substrate) fluorescence was 1.58-fold higher in cells pretreated with 60 μM curcumin than in untreated cells, indicating that curcumin inhibited the transport function of BCRP. In vivo experiments showed that curcumin reduced BCRP expression in the liver, kidney, duodenum, jejunum and ileum of chicken. Coadministration of curcumin (150 mg/kg) significantly changed the pharmacokinetic behavior of orally administered florfenicol (substrate of chicken BCRP), with a higher area under the curve (35.51 vs. 25.81 h·ug/L) and a higher Cmax values (9.94 vs. 7.61 μg/mL). The bioavailability of orally administered florfenicol was increased from 51.6 to 72.8% by curcumin. Together, our results indicate that curcumin inhibited the expression and efflux function of BCRP in chicken and improved the bioavailability of BCRP substrate florfenicol.

Biochar has demonstrated potential for stabilising high yields and sequestering carbon in dryland farmland, but it is unclear whether biochar affects the carbon sequestration capacity and carbon balance of annual farmland ecosystems. For this purpose, we conducted a plot control trial in salinised farmland in 2019-2021, where we set three treatments, control, and two biochar rates, 0 (CK), 15 (B15), and 30 t/ha (B30). The results showed that biochar application decreased soil organic carbon stocks in the early part of the experiment (first freeze and freeze period); these increased in the later part, and overall, the biochar treatments increased soil organic carbon storage by 3-6% compared with the control. Compared with the control (CK), biochar inhibited the total soil respiration rate and microbial respiration rate significantly (P < 0.05) during the crop growing period compared with the freeze-thaw period. After two years of freeze-thaw cycling, biochar application increased sunflower plant carbon sequestration and net primary productivity and suppressed total soil microbial respiration, thereby increasing net ecosystem productivity. Therefore, the application of biochar is conducive to carbon sequestration in farmland ecosystems and presents a carbon sink effect, thus being a good choice for improving the soil carbon pool and reducing emissions in the northern dry zone.

Abstract Background The lateral habenula (LHb) is an epithalamus nucleus that is evolutionarily conserved and involved in various physiological functions, such as encoding value signals, integrating emotional information, and regulating related behaviors. The cells in the LHb are predominantly glutamatergic and have heterogeneous functions in response to different stimuli. The circuitry connections of the LHb glutamatergic neurons play a crucial role in integrating a wide range of events. However, the circuitry connections of LHb glutamatergic neurons in both sexes have not been thoroughly investigated. Methods In this study, we injected Cre-dependent retrograde trace virus and anterograde synaptophysin-labeling virus into the LHb of adult male and female Vglut2-ires-Cre mice, respectively. We then quantitatively analyzed the input and output of the LHb glutamatergic connections in both the ipsilateral and contralateral whole brain. Results Our findings showed that the inputs to LHbvGlut2 neurons come from more than 30 brain subregions, including the cortex, striatum, pallidum, thalamus, hypothalamus, midbrain, pons, medulla, and cerebellum with no significant differences between males and females. The outputs of LHbvGlut2 neurons targeted eight large brain regions, primarily focusing on the midbrain and pons nuclei, with distinct features in presynaptic bouton across different brain subregions. While correlation and cluster analysis revealed differences in input and collateral projection features, the input-output connection pattern of LHbvGlut2 neurons in both sexes was highly similar. Conclusions This study provides a systematic and comprehensive analysis of the input and output connections of LHbvGlut2 neurons in male and female mice, shedding light on the anatomical architecture of these specific cell types in the mouse LHb. This structural understanding can help guide further investigations into the complex functions of the LHb.

Abstract Periodontitis is a highly prevalent disease characterized by inflammation and destruction of tooth-supporting tissues that leads to tooth loss in extreme situations. Elucidating the underlying mechanisms of periodontitis pathogenesis and progression will establish the groundwork for developing effective treatment strategies. Recently, evidence concerning the role of ferroptosis in periodontitis progression has emerged. Osteogenic lineage cells are key regulators of bone remodeling. Osteogenic cell death, as observed in experimental periodontitis models, disrupts the balance between bone resorption and bone formation. However, whether the osteogenic lineage undergoes ferroptosis during periodontitis and the corresponding effect on periodontitis progression remain elusive. Here, we investigated cell-specific ferroptosis within the alveolar bone in a murine periodontitis model. Through immunofluorescence double staining and immunohistochemistry, we identified ferroptotic osteocytes and osteoblasts in inflammatory alveolar bone. Next, in vivo administration of erastin or liproxstatin-1 was conducted to either induce or inhibit ferroptosis, respectively. Severe bone resorption and inflammation, accompanied by increased osteoclast formation and impaired osteogenic potential were detected following ferroptosis activation. Subsequently, we carried out in vitro experiments on osteocytes and further verified that ferroptosis enhanced the osteocytic expression of RANKL and IL-6. These findings suggest that ferroptosis occurring within the osteogenic lineage acts as a catalyst in the progression of periodontitis by stimulating osteoclastogenesis through the secretion of inflammatory cytokines and inhibiting osteoblastic function, providing insights into ferroptosis-induced alterations in microenvironment-based intercellular communication. Ferroptosis is a promising target for controlling inflammation and preventing bone resorption in periodontitis.

Abstract Background The gibberellic acid (GA) inhibitor, uniconazole, is a plant growth regulator commonly used in banana cultivation to promote dwarfing but also enhances the cold resistance in plants. However, the mechanism of this induced cold resistance remains unclear. Results We confirmed that uniconazole induced cold tolerance in bananas and that the activities of Superoxide dismutase and Peroxidase were increased in the uniconazole-treated bananas under cold stress when compared with the control groups. The transcriptome and metabolome of bananas treated with or without uniconazole were analyzed at different time points under cold stress. Compared to the control group, differentially expressed genes (DEGs) between adjacent time points in each uniconazole-treated group were enriched in plant-pathogen interactions, MAPK signaling pathway, and plant hormone signal transduction, which were closely related to stimulus-functional responses. Furthermore, the differentially abundant metabolites (DAMs) between adjacent time points were enriched in flavone and flavonol biosynthesis and linoleic acid metabolism pathways in the uniconazole-treated group than those in the control group. Temporal analysis of DEGs and DAMs in uniconazole-treated and control groups during cold stress showed that the different expression patterns in the two groups were enriched in the linoleic acid metabolism pathway. In addition to strengthening the antioxidant system and complex hormonal changes caused by GA inhibition, an enhanced linoleic acid metabolism can protect cell membrane stability, which may also be an important part of the cold resistance mechanism of uniconazole treatment in banana plants. Conclusions This study provides information for understanding the mechanisms underlying inducible cold resistance in banana, which will benefit the production of this economically important crop.

Abstract Lymphatic invasion (LI) is extremely aggressive and induces worse prognosis among patients with colorectal cancer (CRC). Thus, it is critical to characterize the cellular and molecular mechanisms underlying LI in order to establish novel and efficacious therapeutic targets that enhance the prognosis of CRC patients. RNA-seq data, clinical and survival information of colon adenocarcinoma (COAD) patients were obtained from the TCGA database. In addition, three scRNA-seq datasets of CRC patients were acquired from the GEO database. Data analyses were conducted with the R packages. We assessed the tumor microenvironment (TME) differences between LI+ and LI− based scRNA-seq data, LI+ cells exhibited augmented abundance of immunosuppression and invasive subset. Marked extracellular matrix network activation was also observed in LI+ cells within SPP1+ macrophages. We revealed that an immunosuppressive and pro-angiogenic TME strongly enhanced LI, as was evidenced by the CD4+ Tregs, CD8+ GZMK+, SPP1+ macrophages, e-myCAFs, and w-myCAFs subcluster infiltrations. Furthermore, we identified potential LI targets that influenced tumor development, metastasis, and immunotherapeutic response. Finally, a novel LIRS model was established based on the expression of 14 LI-related signatures, and in the two testing cohorts, LIRS was also proved to have accurate prognostic predictive ability. In this report, we provided a valuable resource and extensive insights into the LI of CRC. Our conclusions can potentially benefit the establishment of highly efficacious therapeutic targets as well as diagnostic biomarkers that improve patient outcomes.

ABSTRACTThis study prepared ultralow electron-loss perovskites with spinel-like structures via a solid-state reaction. The (Mg0.95Co0.05)2(Ti0.95Sn0.05)O4 (MCTS) ceramic exhibited approximate values for ultrahigh quality factor, permittivity, and negative temperature coefficient (τf) of 310,000 GHz, 14.25, and −48.1 ppm/oC, respectively. To bring the τf closer to zero, a trace amount of (Ca0.95Sr0.05)(Ti0.97Sn0.03)O3 (CSTS) perovskite was added to MCTS during ceramic manufacturing. CSTS exhibited a permittivity of 92 and a large positive τf value of 810 ppm/°C. A 0.92MCTS–0.08CSTS hybrid ceramic sintered at 1325°C achieved remarkable microwave dielectric properties of εr ~18.42, Q×f ~ 237,000 GHz and τf ~3.72 ppm/°C. This mixed ceramic has significant potential for applications in manufacturing microwave devices.

Abstract Background This study aimed to investigate the turnover intention among nurses in eastern China and explore the association between turnover intention and personal characteristics, family factors, and work-related factors. Methods A total of 2504 nurses participated in a cross-sectional survey administered in 26 hospitals in Eastern China from October to November 2017. In December 2021, a survey was conducted on nurses who resigned between December 2017 and November 2021. Results The turnover intention score of in-service nurses was 15 (12–17), and 43% of nurses had a high turnover intention, which was mainly due to the following reasons: age 1 child, low income, involuntary career selection, frequent night shifts, informal employment, part-time, and high job stress are significant factors associated with nurses’ willingness to leave. Government and hospital administrators should consider ways to address these factors to retain nurses in hospitals in eastern China and improve the quality of nursing services.

Objective To analyze the serological characteristics and molecular mechanism of a novel B subtype allele 803delC. Methods ABO blood group was detected by serological method. Sequence-specific primer polymerase chain reaction (PCR-SSP) was used to detect ABO blood group genes. The coding region of exon 1-7 of ABO gene was detected by Sanger sequencing to determine the mutation site. Results Serological identification of patients was with forward O-type and reverse B-type. The result of PCR-SSP genotyping was A/O. There was A gene, which was not consistent with serological results. Further Sanger double-strand sequencing revealed that the C-base was deleted at position 803 of exon 7 on the basis of ABO*B. 01/ABO*O. 01.01. The mutation eventually leads to the amino acid substitution of p. Ala268Gly and p. Phe269Ser and the production of new open reading frame starting at position 269, with the new open reading frame No.20 amino acid being stop codon, resulted in the termination of B gene expression. Further single-strand sequencing of the ABO gene revealed that the mutation was located in the ABO*B. 01 gene. The mutation was submitted to the NCBI database with the number OR343908. Conclusion A new ABO allele leading to B variant has been found in Chinese population. Genetic detection can be used to identify the ambiguous blood group with discrepancy between forward and reverse blood grouping.

【Objective】The study was conducted to screen plant growth regulators that could shorten the plant height of banana without affecting the yield, and explore the dwarfing effects of their application times on banana plants. Furthermore, appropriate concentrations of uniconazole were detected for identifying the changes in the activities of several defensive antioxidant enzymes, and the contents of soluble protein, potassium, calcium, magnesium and phosphorus in banana leaves, to further analyze the positive auxiliary effect of uniconazole on banana plant growth in addition to dwarfing effect, which would provide references for the safe and rational use of plant growth regulators in banana production.【Method】The dwarfing effects of several plant growth regulators including uniconazole (XX), paclobutrazol (DX), chlormequat chloride (AZ), mepiquat (JP), compound agents 0802 and 0501 on banana plants were evaluated by root spraying method. The contents of polyphenol oxidase (PPO), superoxide dismutase (SOD), catalase (CAT), phenylalanine ammonia lyase (PAL), soluble protein, potassium, calcium, magnesium and phosphorus in banana leaves were determined after 15, 20 and 25 days of 0.3 g/plant XX treatment.【Result】According to the evaluation standard of dwarfing effect, banana plant could grow normally in the 3-5 level of internode distance after dwarfing. Under one dwarfing treatment, the banana plant heights of XX1, DX1, 0501, XX3, JP2, 0802, AZ1 and JP4 treatments were decreased by 11.67-24.00 cm. The banana plant heights of JP2, DX1, JP4, 0802, AZ1, 0501 and XX3 under two dwarfing treatments were decreased by 29.67-39.00 cm with normal growth. It found that the banana plant height was shortened with the increase of the concentrations and application times of these grow regulators. XX3, 0802 and 0501 treatments could promote the early bud shooting of banana, and the duration periods were 8-19 days earlier than that of the control; The plant shooting was neat. The shooting rate of XX3 under two drarfing and 0802 treatment was 62.01% and 89.32%. The yield per plant showed decreasing trends with the increase of XX concentration. The plant yields of banana were 27.26, 25.62 and 23.45 kg for the one time treatment of XX1, XX3 and XX5, respectively. Of which, the yields per plant of XX3 and XX5 treatment were significantly decreased compared with that of the control (27.45 kg). The yields per plant of banana treated with 0802 and 0501 were 27.37 and 26.99 kg, respectively, and there was no significant difference with that of the control. It was found that the yield performance of banana plants was similar under the two dwarfing treatments of different plant grow regulators. Under the treatment with low concentrations of chlormequat chloride and paclobutrazol, the early shooting of banana could be promoted. Whereas the shooting of banana was delayed when the treating concentration was above 0.2 g per plant, and the plant yield was greatly affected or even reduced. The uniconazole treatment could increase the activities of PPO, CAT and PAL in banana leaves as well as the contents of soluble protein, calcium, magnesium, phosphorus and potassium, and enhance plant resistance.【Conclusion】It is recommended to use uniconazole, compound agents 0802 and 0501 as banana dwarfing agents with concentration ranging of 0.2-0.3 g/plant in banana production, and the newly planted banana could be dwarfed once. Banana is more susceptible to paclobutrazol (DX) and chlormequat chloride (AZ), which are not recommended.

Objective To reveal the sources and ecological risks of heavy metals in a typical lead-zinc mining area in Hebei Province, 156 soil samples were collected around a zinc mining area in Hebei Province through a systematic field sampling method. Methods The sources of heavy metals in the area were analysed via principal component analysis(PCA) and a positive matrix factorization(PMF) model. The risk assessment was carried out according to the index of geoaccumulation method and potential ecological risk index method. Results The results show that the mean values of Cr, Ni, Cu, Zn, As, Cd, Pb and Hg are 53.6, 25.7, 62.7, 692, 10.6, 1.75, 142, 0.129 mg/kg, respectively. Except for Cr, Ni and As, the other 5 elements present at different pollution levels. Above the background values of the soils in Hebei Province, the coefficient of variation of Hg, Cd, Zn, Pb and Cu is more than 1.75, and the coefficient of variation of As exceeds 0.5, indicating the high variability of these 6 elements. The results of the source analysis reveal that the main sources of soil heavy metals include mining activities, natural sources, agricultural activities, and gold smelting. Zn, Cd and Pb were mainly derived from mining activities; Cr and Ni were influenced by natural parent materials and were derived from natural sources; Cu was mainly derived from agricultural activities and mining activities; As was controlled by natural sources, mining activities and agricultural activities; and Hg was originated from mainly gold smelting and mining activities. The combination of PCA and the PMF model to corroborate each other facilitates the reliability of the heavy metal source analysis results. Conclusion There is anthropogenic Hg and Cd contamination in this area, as indicated by the high geoaccumulation indices and potential ecological risk indices. In addition, the ecological risk in general was found to be very high, and attention needs to be given to and management work to be carried out.