Voxel-Wise Fusion of 3T and 7T Diffusion MRI Data to Extract more Accurate Fiber Orientations.

While 7T diffusion magnetic resonance imaging (dMRI) has high spatial resolution, its diffusion imaging quality is usually affected by signal loss due to B1 inhomogeneity, T2 decay, susceptibility, and chemical shift. In contrast, 3T dMRI has relative higher diffusion angular resolution, but lower spatial resolution. Combination of 3T and 7T dMRI, thus, may provide more detailed and accurate information about the voxel-wise fiber orientations to better understand the structural brain connectivity. However, this topic has not yet been thoroughly explored until now. In this study, we explored the feasibility of fusing 3T and 7T dMRI data to extract voxel-wise quantitative parameters at higher spatial resolution. After 3T and 7T dMRI data was preprocessed, respectively, 3T dMRI volumes were coregistered into 7T dMRI space. Then, 7T dMRI data was harmonized to the coregistered 3T dMRI B0 (b = 0) images. Last, harmonized 7T dMRI data was fused with 3T dMRI data according to four fusion rules proposed in this study. We employed high-quality 3T and 7T dMRI datasets (N = 24) from the Human Connectome Project to test our algorithms. The diffusion tensors (DTs) and orientation distribution functions (ODFs) estimated from the 3T-7T fused dMRI volumes were statistically analyzed. More voxels containing multiple fiber populations were found from the fused dMRI data than from 7T dMRI data set. Moreover, extra fiber directions were extracted in temporal brain regions from the fused dMRI data at Otsu's thresholds of quantitative anisotropy, but could not be extracted from 7T dMRI dataset. This study provides novel algorithms to fuse intra-subject 3T and 7T dMRI data for extracting more detailed information of voxel-wise quantitative parameters, and a new perspective to build more accurate structural brain networks.

[Effect of Erchen Decoction on liver mitochondrial function by inhibiting mTORC1/SREBP1/CAV1 pathway in mice with high-fat diet].

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.

Dual-core-component multiphasic bioceramic granules with selective-area porous structures facilitating bone tissue regeneration and repair.

Ca-phosphate/-silicate ceramic granules have been widely studied because their biodegradable fillers can enhance bone defect repair accompanied with bioactive ion release and material degradation; however, it is a challenge to endow bioceramic composites with time-dependent ion release and highly efficient osteogenesis in vivo. Herein, we prepared dual-core-type bioceramic granules with varying chemical compositions beneficial for controlling ion release and stimulating osteogenic capability. Core-shell-structured bioceramic granules (P8-Sr4@Zn3, P8-Sr4@TCP, and P8-Sr4@HAR) composed of 8% P- and 4% Sr-substituting wollastonite (P8, Sr4) dual core components and different shell components, such as 3% Zn-substituting wollastonite (Zn3), ß-tricalcium phosphate (ß-TCP), and hardystonite (HAR), were prepared by cutting extruded core-shell fibers through dual-core ternary nozzles, followed by high-temperature sintering post-treatment. The experimental results showed that nonstoichiometric wollastonite core components contributed to more biologically active ion release in Tris buffer in vitro, and the sparingly dissolvable shell component readily maintained the granule morphology in vivo; thus, such bioceramic implants can adjust new bone growth and material degradation over time. In particular, bioceramic granules encapsulated by the TCP shell exhibited the most appreciable osteogenic capacity and expected biodegradation, which was mostly favorable for bone repair in critical bone defects. It is reasonable to consider that this new multiphasic bioceramic granule design is versatile for developing next-generation implants for various bone damage repairs.

Effects of lipids on the rate-limiting steps in the dark-to-light transition of Photosystem II core complex of Thermostichus vulcanus.

In our earlier works, we have shown that the rate-limiting steps, associated with the dark-to-light transition of Photosystem II (PSII), reflecting the photochemical activity and structural dynamics of the reaction center complex, depend largely on the lipidic environment of the protein matrix. Using chlorophyll-a fluorescence transients (ChlF) elicited by single-turnover saturating flashes, it was shown that the half-waiting time (Δτ 1/2) between consecutive excitations, at which 50% of the fluorescence increment was reached, was considerably larger in isolated PSII complexes of Thermostichus (T.) vulcanus than in the native thylakoid membrane (TM). Further, it was shown that the addition of a TM lipid extract shortened Δτ 1/2 of isolated PSII, indicating that at least a fraction of the 'missing' lipid molecules, replaced by detergent molecules, caused the elongation of Δτ 1/2. Here, we performed systematic experiments to obtain information on the nature of TM lipids that are capable of decreasing Δτ 1/2. Our data show that while all lipid species shorten Δτ 1/2, the negatively charged lipid phosphatidylglycerol appears to be the most efficient species - suggesting its prominent role in determining the structural dynamics of PSII reaction center.

Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice.

INTRODUCTION: Inflammatory bowel disease (IBD) is a global disease with limited therapy. It is reported that sedanolide exerts anti-oxidative and anti-inflammatory effects as a natural phthalide, but its effects on IBD remain unclear. OBJECTIVES: In this study, we investigated the impacts of sedanolide on dextran sodium sulfate (DSS)-induced colitis in mice. METHODS: The mice were administered sedanolide or vehicle followed by DSS administration, after which colitis symptoms, inflammation levels, and intestinal barrier function were evaluated. Transcriptome analysis, 16S rRNA sequencing, and targeted metabolomics analysis of bile acids and lipids were performed. RESULTS: Sedanolide protected mice from DSS-induced colitis, suppressed the inflammation, restored the weakened epithelial barrier, and modified the gut microbiota by decreasing bile salt hydrolase (BSH)-expressing bacteria. The downregulation of BSH activity by sedanolide increased the ratio of conjugated/unconjugated bile acids (BAs), thereby inhibiting the intestinal farnesoid X receptor (FXR) pathway. The roles of the FXR pathway and gut microbiota were verified using an intestinal FXR-specific agonist (fexaramine) and germ-free mice, respectively. Furthermore, we identified the key effector ceramide, which is regulated by sphingomyelin phosphodiesterase 3 (SMPD3). The protective effects of ceramide (d18:1/16:0) against inflammation and the gut barrier were demonstrated in vitro using the human cell line Caco-2. CONCLUSION: Sedanolide could reshape the intestinal flora and influence BA composition, thus inhibiting the FXR-SMPD3 pathway to stimulate the synthesis of ceramide, which ultimately alleviated DSS-induced colitis in mice. Overall, our research revealed the protective effects of sedanolide against DSS-induced colitis in mice, which indicated that sedanolide may be a clinical treatment for colitis. Additionally, the key lipid ceramide (d18:1/16:0) was shown to mediate the protective effects of sedanolide, providing new insight into the associations between colitis and lipid metabolites.

Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.

In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice. CD4+ T cell-specific deletion of Bhlhe40 abrogates Th1 but augments Tfh differentiation. We also assessed an increase in germinal center B cells and Ab production, suggesting that deletion of Bhlhe40 in CD4+ T cells not only alters Tfh differentiation but also their capacity to provide help to B cells. To identify molecular mechanisms by which Bhlhe40 regulates Th1 versus Tfh lineage choice, we first performed epigenetic profiling in the virus specific Th1 and Tfh cells following LCMV infection, which revealed distinct promoter and enhancer activities between the two helper cell lineages. Furthermore, we identified that Bhlhe40 directly binds to cis-regulatory elements of Th1-related genes such as Tbx21 and Cxcr6 to activate their expression while simultaneously binding to regions of Tfh-related genes such as Bcl6 and Cxcr5 to repress their expression. Collectively, our data suggest that Bhlhe40 functions as a transcription activator to promote Th1 cell differentiation and a transcription repressor to suppress Tfh cell differentiation.

Gastric Cancer Immune Subtypes and Prognostic Modeling: Insights from Aging-Related Gene Analysis.

Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, ß-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. In vitro, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-ß-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.

A magnetic calcium phosphate for selective capture of multi-phosphopeptides.

The specific enrichment of multi-phosphopeptides in the presence of non-phosphopeptides and mono-phosphopeptides was still a challenge for phosphoproteomics research. Most of these enrichment materials relied on Zn, Ti, Sn, and other rare precious metals as the bonding center to enrich multi-phosphopeptides while ignoring the use of common metal elements. The addition of rare metals increased the cost of the experiment, which was not conducive to their large-scale application in biomedical proteomics laboratories. In addition, multiple high-speed centrifugation steps also resulted in the loss of low-abundance multi-phosphopeptides in the treatment procedure of biological samples. This study proposed the use of calcium, a common element, as the central bonding agent for synthesizing magnetic calcium phosphate materials (designated as CaP-Fe3O4). These materials aim to capture multi-phosphopeptides and identifying phosphorylation sites. The current results demonstrate that CaP-Fe3O4 exhibited excellent selection specificity, high sensitivity, and stability in the enrichment of multi-phosphopeptides and the identification of phosphorylation sites. Additionally, the introduction of magnetic separation not only reduced the time required for multi-phosphopeptides enrichment but also prevented the loss of these peptides during high-speed centrifugation. These findings contribute to the widespread application and advancement of phosphoproteomics research.

Methylomonas defluvii sp. nov., a type I methane-oxidizing bacterium from a secondary sedimentation tank of a wastewater treatment plant.

An aerobic methanotroph was isolated from a secondary sedimentation tank of a wastewater treatment plant and designated strain OY6T. Cells of OY6T were Gram-stain-negative, pink-pigmented, motile rods and contained an intracytoplasmic membrane structure typical of type I methanotrophs. OY6T could grow at a pH range of 4.5-7.5 (optimum pH 6.5) and at temperatures ranging from 20 °C to 37 °C (optimum 30 °C). The major cellular fatty acids were C14 : 0, C16 : 1ω7c/C16 : 1ω6c and C16 : 1ω5c; the predominant respiratory quinone was MQ-8. The genome size was 5.41 Mbp with a DNA G+C content of 51.7 mol%. OY6T represents a member of the family Methylococcaceae of the class Gammaproteobacteria and displayed 95.74-99.64 % 16S rRNA gene sequence similarity to the type strains of species of the genus Methylomonas. Whole-genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridisation (dDDH) confirmed that OY6T should be classified as representing a novel species. The most closely related type strain was Methylomonas fluvii EbBT, with 16S rRNA gene sequence similarity, ANI by blast (ANIb), ANI by MUMmer (ANIm) and dDDH values of 99.64, 90.46, 91.92 and 44.5 %, respectively. OY6T possessed genes encoding both the particulate methane monooxygenase enzyme and the soluble methane monooxygenase enzyme. It grew only on methane or methanol as carbon sources. On the basis of phenotypic, genetic and phylogenetic data, strain OY6T represents a novel species within the genus Methylomonas for which the name Methylomonas defluvii sp. nov. is proposed, with strain OY6T (=GDMCC 1.4114T=KCTC 8159T=LMG 33371T) as the type strain.

Development of calcium-modified biochar for enhanced phytoremediation of human-induced salt pollutants (HISPs).

Soil salinization is a major environmental hazard that limits land availability. Human-induced salt pollutants (HISPs) are regularly presented in large quantities on the contaminated site (such as brine leakages and salt-water spills), causing a devastating shock with high salt stress to the ecosystem. For instance, Saskatchewan resulted in a 48% drop in wheat production and a 0.3% decline in provincial GDP. As the calcium-modified biochar can potentially ameliorate the negative effects of HISPs on plants and improve the plant, phytoremediation with calcium-modified biochar can have increased detoxification of hazardous pollutants from sites. Therefore, the objective of our study was to develop a biochar-assisted phytoremediation employing diverse approaches to calcium modification for the sustainable removal of HISPs. The co-pyrolyzed calcium biochar achieved a remarkable removal rate of 18.06%, reducing salinity from 9.44 to 7.81 dS/m. During a 90-day long-term phytoremediation, the overall reduction rate of calcium-modified biochar stimulated the germination and growth of Thinopyrum ponticum. The result of post-treatment further indicated that co-pyrolyzed biochar with Ca transferred salt into the plant compared to Ca-coated biochar, which only immobilized HISPs on its surface. These results offer two different treatment approaches for diverse situations involving HISPs contamination, addressing current in-situ spills and providing a calcium-related biochar technology for further research in desalination.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

A lasso and random forest model using flow cytometry data identifies primary myelofibrosis.

Thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), prefibrotic/early (pre-PMF), and overt fibrotic PMF (overt PMF) are classical Philadelphia-Negative (Ph-negative) myeloproliferative neoplasms (MPNs). Differentiating between these types based on morphology and molecular markers is challenging. This study aims to clarify the application of flow cytometry in the diagnosis and differential diagnosis of classical MPNs. This study retrospectively analyzed the immunophenotypes, clinical characteristics, and laboratory findings of 211 Ph-negative MPN patients, including ET, PV, pre-PMF, overt PMF, and 47 controls. Compared to ET and PV, PMF differed in white blood cells, hemoglobin, blast cells in the peripheral blood, abnormal karyotype, and WT1 gene expression. PMF also differed from controls in CD34+ cells, granulocyte phenotype, monocyte phenotype, percentage of plasma cells, and dendritic cells. Notably, the PMF group had a significantly lower plasma cell percentage compared with other groups. A lasso and random forest model select five variables (CD34+CD19+cells and CD34+CD38- cells on CD34+cells, CD13dim+CD11b- cells in granulocytes, CD38str+CD19+/-plasma, and CD123+HLA-DR-basophils), which identify PMF with a sensitivity and specificity of 90%. Simultaneously, a classification and regression tree model was constructed using the percentage of CD34+CD38- on CD34+ cells and platelet counts to distinguish between ET and pre-PMF, with accuracies of 94.3% and 83.9%, respectively. Flow immunophenotyping aids in diagnosing PMF and differentiating between ET and PV. It also helps distinguish pre-PMF from ET and guides treatment decisions.

Molecular-level insight into the chlorofluorocarbons adsorption by defective covalent organic polymers.

Halocarbons have important industrial applications, however they contribute to global warming and the fact that they can cause ozone depletion. Hence, the techniques that can capture and recover the used halocarbons with energy efficiency methods have recently received greater attention. In this contribution, we report the capture of dichlorodifluoromethane (R12), which has high global warming and ozone depletion potential, using covalent organic polymers (COPs). The defect-engineered COPs were synthesized and demonstrated outstanding sorption capacities, ~226 wt% of R12 combined with linear-shaped adsorption isotherms. We further identified the plausible microscopic adsorption mechanism of the investigated COPs via grand canonical Monte Carlo simulations applied to non-defective and a collection of atomistic models of the defective COPs. The modeling work suggests that significant R12 adsorption is attributed to a gradual increment of porosities due to isolated/interconnected micro-/meso-pore channels and the change of the long-range ordering of both COPs. The successive hierarchical-pore-filling mechanism promotes R12 molecular adsorption via moderate van der Waals adsorbate-adsorbent interactions in the micropores of both COPs at low pressure followed by adsorbate-adsorbate interactions in the extra-voids created at moderate to high pressure ranges. This continuous pore-filling mechanism makes defective COPs as promising sorbents for halocarbon adsorption.

Reconstruction of the genome-scale metabolic network model of Sinorhizobium fredii CCBAU45436 for free-living and symbiotic states.

Sinorhizobium fredii CCBAU45436 is an excellent rhizobium that plays an important role in agricultural production. However, there still needs more comprehensive understanding of the metabolic system of S. fredii CCBAU45436, which hinders its application in agriculture. Therefore, based on the first-generation metabolic model iCC541 we developed a new genome-scale metabolic model iAQY970, which contains 970 genes, 1,052 reactions, 942 metabolites and is scored 89% in the MEMOTE test. Cell growth phenotype predicted by iAQY970 is 81.7% consistent with the experimental data. The results of mapping the proteome data under free-living and symbiosis conditions to the model showed that the biomass production rate in the logarithmic phase was faster than that in the stable phase, and the nitrogen fixation efficiency of rhizobia parasitized in cultivated soybean was higher than that in wild-type soybean, which was consistent with the actual situation. In the symbiotic condition, there are 184 genes that would affect growth, of which 94 are essential; In the free-living condition, there are 143 genes that influence growth, of which 78 are essential. Among them, 86 of the 94 essential genes in the symbiotic condition were consistent with the prediction of iCC541, and 44 essential genes were confirmed by literature information; meanwhile, 30 genes were identified by DEG and 33 genes were identified by Geptop. In addition, we extracted four key nitrogen fixation modules from the model and predicted that sulfite reductase (EC 1.8.7.1) and nitrogenase (EC 1.18.6.1) as the target enzymes to enhance nitrogen fixation by MOMA, which provided a potential focus for strain optimization. Through the comprehensive metabolic model, we can better understand the metabolic capabilities of S. fredii CCBAU45436 and make full use of it in the future.

microRNA-486-5p Regulates DNA Damage Inhibition and Cisplatin Resistance in Lung Adenocarcinoma by Targeting AURKB.

Lung adenocarcinoma (LUAD) severely affects human health, and cisplatin (DDP) resistance is the main obstacle in LUAD treatment, the mechanism of which is unknown. Bioinformatics methods were utilized to predict expression and related pathways of AURKB in LUAD tissues, as well as the upstream regulated microRNAs. qRT-PCR assayed expression of AURKB and microRNA-486-5p. RIP and dual-luciferase experiments verified the binding and interaction between the two genes. CCK-8 was used to detect cell proliferation ability and IC50 values. Flow cytometry was utilized to assess the cell cycle. Comet assay and western blot tested DNA damage and γ-H2AX protein expression, respectively. In LUAD, AURKB was upregulated, but microRNA-486-5p was downregulated. The targeted relationship between the two was confirmed by RIP and dual-luciferase experiments. Cell experiments showed that AURKB knock-down inhibited cell proliferation, reduced IC50 values, induced cell cycle arrest, and caused DNA damage. The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.

Coexistence of blaIMP-4 and blaSFO-1 in an IncHI5B plasmid harbored by tigecycline-non-susceptible Klebsiella variicola strain.

BACKGROUND: Klebsiella variicola is considered a newly emerging human pathogen. Clinical isolates of carbapenemase and broad-spectrum ß-lactamase-producing K. variicola remain relatively uncommon. A strain of K. variicola 4253 was isolated from a clinical sample, and was identified to carry the blaIMP-4 and blaSFO-1 genes. This study aims to discern its antibiotic resistance phenotype and genomic characteristics. METHODS: Species identification was conducted using MALDI-TOF/MS. PCR identification confirmed the presence of the blaIMP-4 and blaSFO-1 genes. Antibiotic resistance phenotype and genomic characteristics were detected by antimicrobial susceptibility testing and whole-genome sequencing. Plasmid characterization was carried out through S1-PFGE, conjugation experiments, Southern blot, and comparative genomic analysis. RESULTS: K. variicola 4253 belonged to ST347, and demonstrated resistance to broad-spectrum ß-lactamase drugs and tigecycline while being insensitive to imipenem and meropenem. The blaIMP-4 and blaSFO-1 genes harbored on the plasmid p4253-imp. The replicon type of p4253-imp was identified as IncHI5B, representing a multidrug-resistant plasmid capable of horizontal transfer and mediating the dissemination of drug resistance. The blaIMP-4 gene was located on the In809-like integrative element (Intl1-blaIMP-4-aacA4-catB3), which circulates in Acinetobacter and Enterobacteriaceae. CONCLUSIONS: This study reports the presence of a strain of K. variicola, which is insensitive to tigecycline, carrying a plasmid harboring blaIMP-4 and blaSFO-1. It is highly likely that the strain acquired this plasmid through horizontal transfer. The blaIMP-4 array (Intl1-blaIMP-4-aacA4-catB3) is also mobile in Acinetobacter and Enterobacteriaceae. So it is essential to enhance clinical awareness and conduct epidemiological surveillance on multidrug-resistant K. variicola, conjugative plasmids carrying blaIMP-4, and the In809 integrative element.

Mediator complex subunit 1 architects a tumorigenic Treg cell program independent of inflammation.

While immunotherapy has revolutionized cancer treatment, its safety has been hampered by immunotherapy-related adverse events. Unexpectedly, we show that Mediator complex subunit 1 (MED1) is required for T regulatory (Treg) cell function specifically in the tumor microenvironment. Treg cell-specific MED1 deletion does not predispose mice to autoimmunity or excessive inflammation. In contrast, MED1 is required for Treg cell promotion of tumor growth because MED1 is required for the terminal differentiation of effector Treg cells in the tumor. Suppression of these terminally differentiated Treg cells is sufficient for eliciting antitumor immunity. Both human and murine Treg cells experience divergent paths of differentiation in tumors and matched tissues with non-malignant inflammation. Collectively, we identify a pathway promoting the differentiation of a Treg cell effector subset specific to tumors and demonstrate that suppression of a subset of Treg cells is sufficient for promoting antitumor immunity in the absence of autoimmune consequences.

Ternary solid dispersions of lacidipine: Enhancing dissolution and supersaturation maintenance through strategic formulation optimization.

The study aimed to address the challenges related to insufficient dissolution and maintenance of supersaturation in binary solid dispersions. Lacidipine, categorized as a BCS class II drug, was employed as the model drug. A systematic screening of excipients was conducted to determine the most effective carriers for the formulations of the ternary solid dispersions, utilizing the solvent transfer method and equilibrium solubility measurements. Both binary and ternary solid dispersions were prepared via spray drying, and comprehensive physicochemical characterization confirmed the successful preparation of amorphous solid dispersions. In vitro dissolution tests, the ternary solid dispersion exhibited marked superiority over the binary solid dispersion in dissolution and maintenance of supersaturation. Furthermore, an exploration into the factors influencing the stability of ternary solid dispersions revealed their robust resistance under light-protected, room-temperature, and desiccated conditions. The formation of intermolecular hydrogen bonding within the molecules of the ternary solid dispersions significantly enhanced drug solubility and system stability. Strategic formulation optimization, coupled with judicious selection of suitable carrier types and ratios, may serve as a promising approach for designing supersaturated drug delivery systems.

A study on the effect of using the video teach-back method in continuous nursing care of stroke patients.

Objective: To explore the effect of a video teach-back method on continuous family nursing care of stroke patients. Methods: Stroke patients hospitalized in our hospital between March 2020 and March 2023 who met the inclusion criteria were randomly divided into an intervention group (n = 45), who received routine health education plus video teach-back training of caregivers, and a control group (n = 45), who received routine health education only. The effects on nursing-related variables were compared between the two groups. Results: Total scores representing the caring ability of caregivers in the intervention group increased significantly over time relative to baseline and were higher than those of the control group. Scores representing the care burden of caregivers in the intervention group decreased significantly over time and were lower than those of the control group. Conclusion: The teach-back method combined with video education improves the nursing ability of family caregivers and can improve the self-care ability of stroke patients.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.