The threshold of child protection notifications is higher in municipalities with a high level of risk factors - Is this evidence of the inverse intervention law?

BACKGROUND: Child protection notifications aim to secure the wellbeing of children. However, there is a large variation in the implementation of notifications across the municipalities in Finland. OBJECTIVE: This article explores whether the threshold of child protection notifications is higher in municipalities with a high level of socio-economic risk factors, as assumed by the inverse intervention law. PARTICIPANTS AND SETTING: The study is based on the system-level data of Finnish municipalities, and their socio-economic indicators for the period of 2010-2021. METHODS: A cluster analysis is used to group Finnish municipalities, based on the level of socio-economic risk factors, and a panel regression analysis, to verify whether these factors act as risk factors or as driving forces of inverse intervention law. RESULTS: The municipalities with a high level of risk factors have the higher threshold level for child protection notifications compared to other municipalities. In all municipalities, the share of single-parent families acts as a risk factor, while the share of residents with higher education acts as a driver of the inverse intervention law. Reduction of unemployment and income inequalities are also recognised as drivers of this law, but only in municipalities with a relatively higher level of risk factors. CONCLUSIONS: This study promotes the inverse intervention law, and contribute to the understanding of the driving forces of this law. Further, there is a difference in the threshold level of child protection notifications among municipalities which is based on their socio-economic context. Children are in an unequal position in relation to the municipality in which they live.

Possible role of a malfunctioning immune system in discordant lymphoma with peripheral T­cell lymphoma secondary to classical Hodgkin lymphoma: A case report.

The present case report investigated the clinicopathological features and potential mechanisms underlying the transformation to peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), following treatment for classical Hodgkin lymphoma (CHL) in a 73-year-old man. The patient was admitted to hospital in 2012 and underwent a left cervical lymph node biopsy, which confirmed CHL of the nodular sclerosing type, with evident bone marrow involvement. The patient received four cycles of doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy, after which they achieved complete remission. However, after 3 years, the patient presented with enlarged left inguinal lymph nodes and a biopsy revealed PTCL-NOS. Molecular studies indicated a T-cell receptor-γ gene rearrangement. A literature review, together with the current case, identified 11 patients with CHL that transformed into PTCL-NOS. Among these, nine patients (81.82%) were middle-aged or elderly (>45 years old), and eight (72.73%) experienced transformation within 3 years post-treatment of CHL. Among these eight patients, seven (87.50%) predominantly exhibited the nodular sclerosis subtype, with a median recurrence time of 26 months. Five (45.45%) patients died of the disease. The rare transformation of CHL to PTCL-NOS, primarily among men, underscores its clinical significance. Notably, nodular sclerosing-type CHL appears to be particularly prone to transformation into PTCL-NOS. The poor prognosis in such cases may be attributed to the complex tumor microenvironment of CHL.

Association between C-reactive protein/albumin ratio and all-cause mortality in patients with stroke: Evidence from NHANES cohort study.

BACKGROUND AND AIMS: The inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. METHODS AND RESULTS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. CONCLUSION: Elevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.

Hard X-ray imaging and tomography at the Biomedical Imaging and Therapy beamlines of Canadian Light Source.

The Biomedical Imaging and Therapy facility of the Canadian Light Source comprises two beamlines, which together cover a wide X-ray energy range from 13 keV up to 140 keV. The beamlines were designed with a focus on synchrotron applications in preclinical imaging and veterinary science as well as microbeam radiation therapy. While these remain a major part of the activities of both beamlines, a number of recent upgrades have enhanced the versatility and performance of the beamlines, particularly for high-resolution microtomography experiments. As a result, the user community has been quickly expanding to include researchers in advanced materials, batteries, fuel cells, agriculture, and environmental studies. This article summarizes the beam properties, describes the endstations together with the detector pool, and presents several application cases of the various X-ray imaging techniques available to users.

Nodal T follicular helper cell lymphoma with aberrant CD20 expression and monoclonal TCR, IG rearrangements secondary to Classical Hodgkin Lymphoma: a case report.

Classical Hodgkin Lymphoma (CHL) is a rare malignant neoplasm of the lymphatic system. While CHL typically responds well to conventional treatments, some cases may experience relapse to other subtypes, with the development of secondary peripheral T-cell lymphoma (PTCL) being relatively uncommon. Herein, we report a rare case of nodal T follicular helper cell lymphomas,nos (nTFHL-NOS) secondary to CHL, accompanied by aberrant CD20 expression and clonal rearrangements of T-cell receptor (TCR) and immunoglobulin (IG). A 74-year-old male, was diagnosed with CHL, leaning toward the mixed cell type, 6 years ago. He received six cycles of the Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD) regimen, achieving complete clinical remission. The patient was admitted to our hospital due to the appearance of multiple skin nodules 66 months later. Histopathological analysis revealed nTFHL-NOS, with aberrant CD20 expression and clonal rearrangements of TCR and IG. The patient underwent two cycles of chemotherapy with brentuximab vedotin and the Gemcitabine-Oxaliplatin (G-mox) regimen, resulting in a reduction of the skin lesions to 2 cm × 1 cm. We discuss this rare case and review related literature.

[Mechanism study of 6-shogaol alleviating cerebral ischemia/reperfusion injury by regulating microRNA-26a-5p/death-associated protein kinase 1].

OBJECTIVE: To investigate whether 6-shogaol (6-SH) alleviates oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neuronal autophagy and calcium overload by promoting the expression of microRNA-26a-5p (miR-26a-5p) and inhibiting death-associated protein kinase 1 (DAPK1), and to explore its potential mechanisms. METHODS: Primary cultured logarithmic growth phase mouse hippocampal neurons HT22 cells were taken and cell counting kit-8 (CCK-8) was used to detect cell viability, searching for the optimal concentration of Na2S2O4. HT22 cells were divided into blank control group (NC group), OGD/R group (sugar-free culture medium + 10 mmol/L Na2S2O4 treatment for 1.5 hours followed by normal culture medium for 4 hours), 6-SH intervention group (cultured with 10 µmol/L 6-SH for 4 hours after OGD), negative control inhibitor pretreatment group (transfected with negative control inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours), and miR-26a-5p inhibitor pretreatment group (transfected with miR-26a-5p inhibitor for 48 hours followed by OGD, then cultured with 6-SH for 4 hours). Cell viability of each group was detected by CCK-8 method; cell ultrastructure was observed under transmission electron microscopy; real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the gene expressions of DAPK1 and miR-26a-5p; molecular docking were used to verify the interaction between 6-SH and miR-26a-5p; dual-luciferase assay was used to verify the targeting relationship between DAPK1 and miR-26a-5p; flow cytometry was used to determine the levels of intracellular Ca2+; Western blotting was used to detect the protein expressions of phosphorylated-glutamate receptor 2B (p-NMDAR2B) Ser1303, DAPK1, autophagy related protein Beclin1, light chain 3 (LC3), and p-DAPK1 Ser308; immunofluorescence was used to detect the expression of LC3 and Beclin1. RESULTS: The results of the CCK-8 assay showed that the cell viability of the 6-SH intervention group was significantly increased compared to the OGD/R group, while the cell viability of the miR-26a-5p inhibitor pretreatment group was significantly decreased compared to the 6-SH intervention group. Transmission electron microscopy revealed that the number of autophagosomes in the 6-SH intervention group was significantly reduced compared to the OGD/R group, while the number of autophagosomes in the miR-26a-5p inhibitor pretreatment group was significantly increased compared to the 6-SH intervention group. RT-qPCR results showed that compared with the OGD/R group, the expression of miR-26a-5p was significantly upregulated and the expression of DAPK1 mRNA was significantly downregulated in the 6-SH intervention group; compared with the 6-SH intervention group, the expression of miR-26a-5p was significantly downregulated and the expression of DAPK1 mRNA was significantly upregulated in the miR-26a-5p inhibitor pretreatment group. Molecular docking verified the interaction between 6-SH and miR-26a-5p. Dual-luciferase reporter gene assay showed that compared with the negative control group, mmu-miR-26a-5p significantly downregulated the luciferase expression of m-DAPK1-3UTR-WT, indicating a binding interaction between them. Flow cytometry results showed that compared with the OGD/R group, the level of intracellular Ca2+; was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the level of Ca2+ was significantly increased in the miR-26a-5p inhibitor pretreatment group. Western blotting results showed that compared with the OGD/R group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly decreased in the 6-SH intervention group (p-NMDAR2B Ser1303/ß-actin: 2.34±0.27 vs. 4.78±0.39, DAPK1/ß-actin: 1.40±0.13 vs. 2.37±0.21, Beclin1/ß-actin: 2.61±0.32 vs. 4.32±0.29, LC3/ß-actin: 2.52±0.45 vs. 5.09±0.18, all P < 0.05), while the protein expression of p-DAPK1 Ser308 was significantly increased (p-DAPK1 Ser308/ß-actin: 0.66±0.09 vs. 0.40±0.02, P < 0.05); compared with the 6-SH intervention group, the protein expressions of p-NMDAR2B Ser1303, DAPK1, Beclin1, and LC3 were significantly increased in the miR-26a-5p inhibitor pretreatment group (p-NMDAR2B Ser1303/ß-actin: 4.08±0.14 vs. 2.34±0.27, DAPK1/ß-actin: 1.96±0.15 vs. 1.40±0.13, Beclin1/ß-actin: 3.92±0.31 vs. 2.61±0.32, LC3/ß-actin: 4.33±0.33 vs. 2.52±0.45, all P < 0.05), while the expression of p-DAPK1 Ser308 protein was significantly decreased (p-DAPK1 Ser308/ß-actin: 0.33±0.12 vs. 0.66±0.09, P < 0.05); immunofluorescence staining showed that compared with the OGD/R group, the fluorescence intensity of LC3 and Beclin1 was significantly decreased in the 6-SH intervention group; compared with the 6-SH intervention group, the fluorescence intensity of LC3 and Beclin1 was significantly increased in the miR-26a-5p inhibitor pretreatment group. CONCLUSIONS: 6-SH can alleviate neuronal damage by regulating miR-26a-5p/DAPK1 to reduce autophagy and calcium overload in cells.

Loss-of-function mutation of REV1 (p.R704Q) mediates cetuximab primary resistance by activating autophagy in RAS-wild type metastatic colorectal cancer.

Cetuximab in combination with FOLFIRI/FOLFOX is the standard first-line treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, some patients experience rapid tumor progression after treatment with cetuximab (primary resistance). Our previous research identified a gene mutation, REV1 p.R704Q, which may be a key biomarker for primary cetuximab resistance. This study aimed to study the mechanism of cetuximab resistance caused by REV1 p.R704Q mutation and reveal a novel mechanism to induce cetuximab resistance. Sanger sequencing and multivariate clinical prognostic analysis of 208 patients with mCRC showed that REV1 p.R704Q mutation is an independent risk factor for tumor progression after treatment with cetuximab in patients with RAS wild-type mCRC (Hazard ratio = 2.481, 95 % Confidence interval: 1.389-4.431, P = 0.002). The sensitivity of REV1 p.R704Q mutant cell lines to cetuximab decreased in vitro Cell Counting Kit-8 assay and in vivo subcutaneous tumor model. In vitro, we observed that decreased stability and accelerated degradation of REV1 mutant protein results in REV1 dysfunction, which activated autophagy and mediated cetuximab resistance. These findings suggested that REV1 p.R704Q mutation could predict cetuximab primary resistance in mCRC. REV1 p.R704Q mutation caused decreased stability and degradation of REV1 protein, as well as dysfunction of p.R704Q protein. REV1 p.R704Q mutation activates autophagy and mediates cetuximab resistance; further, inhibition of autophagy could reverse cetuximab resistance.

Role of cspA on the Preparation of Escherichia coli Competent Cells by Calcium Chloride Method.

One of the fundamental techniques in genetic engineering is the creation of Escherichia coli competent cells using the CaCl2 method. However, little is known about the mechanism of E. coli competence formation. We have previously found that the cspA gene may play an indispensable role in the preparation of E. coli DH5α competent cells through multiomics analysis. In the present study, the cellular localization, physicochemical properties, and function of the protein expressed by the cspA gene were analyzed. To investigate the role of the cspA gene in E. coli transformation, cspA-deficient mutant was constructed by red homologous recombination. The growth, transformation efficiency, and cell morphology of the cspA-deficient strain and E. coli were compared. It was found that there were no noticeable differences in growth and morphology between E. coli and the cspA-deficient strain cultured at 37°C, but the mutant exhibited increased transformation efficiencies compared to E. coli DH5α for plasmids pUC19, pET-32a, and p1304, with enhancements of 2.23, 2.24, and 3.46 times, respectively. It was proved that cspA gene is an important negative regulatory gene in the CaCl2 preparation of competent cells.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia.

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model. Based upon the rapid reduction of bone formation and initial elevation of resorption caused by GCs, we hypothesized that the rate of advance (longitudinal erosion rate; LER) of cortical BMUs would be increased. To test this hypothesis we divided 20 female New Zealand White rabbits into four experimental groups: ovariohysterectomy (OVH), glucocorticoid (GC), OVH + GC and SHAM controls (n = 5 animals each). Ten weeks post-surgery (OVH or sham), and two weeks after the initiation of dosing (daily subcutaneous injections of 1.5 mg/kg of methylprednisolone sodium succinate in the GC-treated groups and 1 ml of saline for the others), the right tibiae were scanned in vivo using Synchrotron Radiation (SR) in-line phase contrast micro-CT at the Canadian Light Source. After an additional 2 weeks of dosing, the rabbits were euthanized and ex vivo images were collected using desktop micro-CT. The datasets were co-registered in 3D and LER was calculated as the distance traversed by BMU cutting-cones in the 14-day interval between scans. Counter to our hypothesis, LER was greatly reduced in GC-treated rabbits. Mean LER was lower in GC (4.27 µm/d; p < 0.001) and OVH + GC (4.19 µm/d; p < 0.001), while similar in OVH (40.13 µm/d; p = 0.990), compared to SHAM (40.44 µm/d). This approximately 90 % reduction in LER with GCs was also associated with an overall disruption of BMU progression, with radial expansion of the remodeling space occurring in all directions. This unexpected outcome suggests that GCs do not simply uncouple formation and resorption within cortical BMUs and highlights the value of the time-lapsed 4D approach employed.

Secure optical communication system based on polarization regulation of the data fragmentation multipath transmission technology.

We propose and demonstrate a data fragment multipath transmission scheme to achieve a secure optical communication based on polarization regulation. A dual-polarization Mach-Zehnder modulator (DPMZM) is driven by digital signals which are scattered by field-programmable gate array (FPGA) and transmitted in multiple paths. By utilizing two orthogonal polarization states, we have achieved a signal transmission under different optical parameters, and the transmission rate of the two paths can reach over 10 Gbps through a 20 km fiber with 2.5 Gbps hopping rate. In addition, we establish a theoretical model to analyze the security of the system and simulate brute force cracking; the probability of cracking the minimum information unit is 1.53 × 10-53. This proves that it is difficult to obtain a user data even using the fastest computers. Our scheme has provided, to our knowledge, a new approach for physical layer security.

Non-uniform line-of-sight measurements of nitric oxide using mid-infrared Faraday rotation spectroscopy.

Traditional absorption spectroscopy relies on detecting intensity variations along the line-of-sight to gauge average concentration and temperature. While methods like profile fitting and temperature binning offer insights into the non-uniformity of the path, they fall short of accurately capturing the precise spatial distribution with a single line-of-sight measurement. We propose a novel measurement scheme for non-uniformly distributed concentration of nitric oxide (NO) along the line-of-sight utilizing a single laser and path, by incorporating Faraday rotation spectroscopy with magnetic fields changing over time and space. We validate the proposed scheme by measuring a path of two regions in series with different NO concentrations, and comparing the measurement results with direct absorption spectroscopy of each respective region. In this work, the tuning range of the interband cascade laser used is from 1899.42 to 1900.97 cm-1, encompassing two sets of spectral lines corresponding to the 2Π1/2 and 2Π3/2 transitions of NO's R(6.5). The average relative uncertainty in the concentration measurement for each region is estimated to be within 1.5%, with the concentration for individual absorption cells ranging from 0.2% to 0.8%.

Measurement and spatio-temporal heterogeneity analysis of coupling coordination between development of digital economy and agricultural carbon emission performance.

The new development pattern has identified two key avenues for the sustained advancement of high-quality agricultural and rural development: digitalisation and low-carbon development. The measurement of the digital economy and the agricultural carbon emission performance, and their spatial and temporal heterogeneity, is a crucial step in promoting the spatial coordination and sustainable development of digitalisation and low-carbon agriculture. This paper employs the entropy value method, SBM model, and coupling coordination degree model to investigate the coupling coordination measurement and spatial-temporal heterogeneity of the performance of the digital economy and agricultural carbon emissions. The data used are provincial panel data from 2013 to 2021. The simulation results demonstrate that, between 2013 and 2021, the digital economy of all provinces exhibited varying degrees of growth, yet the development of the digital economy between provinces exhibited a more pronounced tendency to diverge. Concurrently, the agricultural carbon emission efficiency in China exhibited a fluctuating upward trend. The development of the digital economy and the efficiency of agricultural carbon emission were found to be highly coupled. Their coupling and coordination relationship showed a downward trend followed by an upward trend. In general, it is suggested that we should increase investment in digital economy infrastructure and technology, promote digital agricultural applications, strengthen policy guidance and financial support, establish a coupling coordination mechanism and strengthen farmers' digital literacy and environmental awareness.

Magnetic covalent organic frameworks as sorbents in the chromatographic analysis of environmental organic pollutants.

Covalent organic frameworks (COFs) are featured with large specific surface areas, good thermal stability, and abundant pores. These properties are exactly what the sorbents used for extraction or adsorption of interest substances are desired with. While, the low density and hydrophobicity of COFs often makes them difficult to be dispersed evenly and recovered from the aqueous solution. Magnetic covalent organic frameworks (MCOFs) inherit magnetic property of the magnetic particles and porous structure of COFs. They have improved dispersity in aqueous solution and phase separation can be rapidly achieved via external magnetic fields. This review summarized the synthesis strategies for MCOFs, and their application in trace environmental organic pollutants analysis by chromatography techniques. The selection of COFs types and modification with active groups for a certain adsorption purpose is discussed, along with the exploration of adsorption mechanisms, which is beneficial for the design and synthesis of MCOFs.

Exploratory analysis on the association of dietary live microbe and non-dietary prebiotic/probiotic intake with serum cotinine levels in the general adult population.

Background: Previous research has indicated the potential involvement of the microbiota in smoking-related processes. The present study seeks to examine the relationship between dietary live microbes, as well as probiotic or prebiotic consumption, and serum cotinine levels. Methods: This study used data from the National Health and Nutrition Examination Survey 1999-2018. Dietary intake information and probiotic/prebiotic intake data was collected through self-reported questionnaires. Participants were stratified into low, medium, and high intake groups according to their consumption of foods with varying microbial content. Multiple linear models were applied to explore the relationships of dietary live microbes, probiotic or prebiotic use with the serum cotinine level. Results: A total of 42,000 eligible participants were included in the final analysis. The weighted median serum cotinine level was 0.05 (0.01, 10.90) ng/ml. Participants with low, medium, and high dietary microbe intake represented 35.4, 43.6, and 21.0% of the cohort, respectively. Furthermore, participants were stratified into three groups based on their overall consumption of foods with variable microbe contents. The association between dietary live microbe intake and serum cotinine levels remained robust across all models, with medium intake as the reference (Model 2: ß = -0.14, 95% CI: -0.20, -0.07; High: ß = -0.31, 95% CI: -0.39, -0.22). Moreover, both prebiotic and probiotic use exhibited an inverse relationship with serum cotinine levels (Prebiotic: ß = -0.19, 95% CI: -0.37, -0.01; Probiotic: ß = -0.47, 95% CI: -0.64, -0.30). Subgroup analyses revealed no discernible interactions between dietary live microbe, prebiotic, probiotic use, and serum cotinine levels. Conclusion: Our findings suggest a negative correlation between dietary live microbe intake, as well as non-dietary prebiotic/probiotic consumption, and serum cotinine levels.

Association between blood pressure control during aneurysm clipping and functional outcomes in patients with aneurysmal subarachnoid hemorrhage.

Objectives: We explored the relationship between blood pressure variability (BPV) during craniotomy aneurysm clipping and short-term prognosis in patients with aneurysmal subarachnoid hemorrhage to provide a new method to improve prognosis of these patients. Methods: We retrospectively analyzed the differences between patient groups with favorable modified Rankin Scale (mRS ≤ 2) and unfavorable (mRS > 2) prognosis, and examined the association between intraoperative BPV and short-term prognosis. Results: The intraoperative maximum systolic blood pressure (SBPmax, p = 0.005) and the coefficient of variation of diastolic blood pressure (DBPCV, p = 0.029) were significantly higher in the favorable prognosis group. SBPmax (OR 0.88, 95%CI 0.80-0.98) and Neu% (OR 1.22, 95%CI 1.03-1.46) were independent influence factors on prognosis. Patients with higher standard deviations of SBP (82.7% vs. 56.7%; p = 0.030), DBP (82.7% vs. 56.7%; p = 0.030), and DBPCV (82.7% vs. 56.7%; p = 0.030) had more favorable prognosis. Conclusion: Higher SBPmax (≤180 mmHg) during the clipping is an independent protective factor for a 90-day prognosis. These results highlight the importance of blood pressure (BP) control for improved prognosis; higher short-term BPV during clipping may be a precondition for a favorable prognosis.

Soil Organic Matter and Total Nitrogen Reshaped Root-Associated Bacteria Community and Synergistic Change the Stress Resistance of Codonopsis pilosula.

The stress resistance of medicinal plants is essential to the accumulation of pharmacological active ingredients, but the regulation mechanism of biological factors and abiotic factors on medicinal plants is still unclear. To investigate the mechanism of soil nutrient and microecology on the stress resistance of C. pilosula, rhizosphere soil and roots were collected across the four seasons in Minxian, Gansu, and their physicochemical properties, as well as root-associated microorganisms, were examined. The results showed that the bacterial α-diversity indexes increased in the endosphere and rhizosphere from summer to autumn. At the same time, the community composition and function changed considerably. The stability of the endophytic bacterial community was higher than that rhizospheric bacteria, and the complexity of the endophytic bacterial community was lower than rhizospheric bacteria. Soil organic matter (OM), water content (WC), total potassium (TK), and total nitrogen (TN) have been identified as the key factors affecting bacterial community diversity and stress resistance of C. pilosula. WC, TN, and OM showed significant differences from summer to autumn (P < 0.5). Four key soil physiochemical factors changed significantly between seasons (P < 0.01). TN and OM change the stress resistance of C. pilosula mainly by changing the activity of antioxidant enzymes. Changes of OM and endophytic bacterial diversity affect the accumulation of soluble sugars to alter stress resistance. These four key soil physicochemical factors significantly influenced the diversity of endophytic bacteria. WC and OM were identified as the most important factors for endophytic and rhizospheric bacteria, respectively. This study provided the research basis for the scientific planting of C. pilosula.

HighFold: accurately predicting structures of cyclic peptides and complexes with head-to-tail and disulfide bridge constraints.

In recent years, cyclic peptides have emerged as a promising therapeutic modality due to their diverse biological activities. Understanding the structures of these cyclic peptides and their complexes is crucial for unlocking invaluable insights about protein target-cyclic peptide interaction, which can facilitate the development of novel-related drugs. However, conducting experimental observations is time-consuming and expensive. Computer-aided drug design methods are not practical enough in real-world applications. To tackles this challenge, we introduce HighFold, an AlphaFold-derived model in this study. By integrating specific details about the head-to-tail circle and disulfide bridge structures, the HighFold model can accurately predict the structures of cyclic peptides and their complexes. Our model demonstrates superior predictive performance compared to other existing approaches, representing a significant advancement in structure-activity research. The HighFold model is openly accessible at https://github.com/hongliangduan/HighFold.

Exploring the mechanisms underlying effects of bisphenol a on cardiovascular disease by network toxicology and molecular docking.

Background: Globally, cardiovascular disease (CVD) has emerged as a leading cause of mortality. Bisphenol A (BPA), recognized as one of the most prevalent and widely distributed endocrine-disrupting chemicals (EDCs), has been consistently linked to the progression of CVD. This research centers on unraveling the molecular mechanisms responsible for the toxic effects of BPA exposure on CVD. Key targets and pathways involved in action of BPA on CVD were investigated by network toxicology. Binding abilities of BPA to core targets were evaluated by molecular docking. Methods and results: Based on information retrieved from ChEMBL, DrugBank, and OMIM databases, a total of 27 potential targets were found to be associated with the influence of BPA on CVD. Furthermore, the STRING and Cytoscape software were employed to identify three central genes-ESR1, PPARG, and PTGS2-and to construct both the protein-protein interaction network and an interaction diagram of potential targets. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) pathway enrichment analyses via WebGestalt revealed key biological processes (BP), cellular components (CC), molecular functions (MF), and pathways, such as the calcium signaling pathway, inflammatory mediator regulation of TRP channels, gap junction, adrenergic signaling in cardiomyocytes, cGMP-PKG signaling pathway, and cAMP signaling pathway, predominantly involved in BPA-induced CVD toxicity. By using molecular docking investigations, it proved that BPA binds to ESR1, PPARG, and PTGS2 steadily and strongly. Conclusion: This study not only establishes a theoretical framework for understanding the molecular toxicity mechanism of BPA in cardiovascular disease (CVD) but also introduces an innovative network toxicology approach to methodically investigate the influence of environmental contaminants on CVD. This methodology sets the stage for drug discovery efforts targeting CVD linked to exposure to endocrine-disrupting chemicals (EDCs).

Degradation of petroleum hydrocarbon contaminants by Rhodococcus erythropolis KB1 synergistic with alfalfa (Medicago sativa L.).

Petroleum hydrocarbons are a stubborn pollutant that is difficult to degrade globally, and plant-microbial degradation is the main way to solve this type of pollutant. In this study, the physiological and ecological responses of alfalfa to petroleum hydrocarbons in different concentrations of petroleum hydrocarbon-contaminated soil with KB1 (Rhodococcus erythropolis) were analyzed and determined by laboratory potting techniques. The growth of alfalfa (CK) and alfalfa with KB1 (JZ) in different concentrations of petroleum hydrocarbons contaminated soil was compared and analyzed. The results of the CK group showed that petroleum hydrocarbons could significantly affect the activity of alfalfa antioxidant enzyme system, inhibit the development of alfalfa roots and the normal growth of plants, especially in the high-concentration group. KB1 strain had the ability to produce IAA, form biofilm, fix nitrogen, produce betaine and ACC deaminase, and the addition of KB1 could improve the growth traits of alfalfa in the soil contaminated with different concentrations of petroleum hydrocarbons, the content of soluble sugars in roots, and the stress resistance and antioxidant enzyme activities of alfalfa. In addition, the degradation kinetics of the strain showed that the degradation rate of petroleum could reach 75.2% after soaking with KB1. Furthermore, KB1 can efficiently degrade petroleum hydrocarbons in advance and significantly alleviate the damage of high concentration of petroleum hydrocarbons to plant roots. The results showed that KB1 strains and alfalfa plants could effectively enhance the degradation of petroleum hydrocarbons, which provided new ideas for improving bioremediation strategies.