Prognostic significance of ß2-microglobulin decline index in multiple myeloma.

Purpose: To assess the prognostic significance of ß2-microglobulin decline index (ß2M DI) in multiple myeloma (MM). Methods: 150 MM patients diagnosed with MM were enrolled in this study. Cox proportional hazards model was used to analyze the uni- and multivariate prognosis in training cohort (n=105). A new combined prognostic model containing ß2M DI was built up based on the data in training cohort. The validation group was used to verify the model. Results: ß2M DI showed significant correlation with prognosis in both uni- and multivariate analyses and had a good correlation with complete response (CR) rate and deep remission rate. The ROC and calibration curves in validation cohort (n=45) indicated a good predictive performance of the new model. Based on the median risk score of the training group, we classified patients into high- and low- risk groups. In both training and validation groups, patients in the low-risk group had longer overall survival (OS) time than that in the high-risk group (p<0.05). Conclusion: ß2M DI is a good predictive index for predicting treatment response and survival time in MM patients. The prognostic model added with ß2M DI showed a better correlation with OS.

[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.

Association between pro-inflammatory diet and abdominal pain: Cross-sectional and case-control study from UK biobank and NHANES 2017-2020.

BACKGROUND: There is a close association between diet and abdominal pain, however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet. METHODS: This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q) which including abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain. RESULTS: In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02-1.24; p = 0.022), 1.05 (95% CI 1.00-1.09; p = 0.030), 1.26 (95% CI 1.17-1.36; p < 0.001), and 1.10 (95% CI 1.00-1.20; p = 0.044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20-1.77; p < 0.001), 1.75 (95% CI 1.20-2.60; p = 0.005), 1.45 (95% CI 1.14-1.87; p = 0.003), and 1.18 (95% CI 0.82-1.72; p = 0.380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (p nonlinear <0.001). CONCLUSION: Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.

Relationships among gut microbiota, plasma metabolites, and juvenile idiopathic arthritis: a mediation Mendelian randomization study.

Objective: The objective of this study is to investigate the causal relationship between gut microbiota and juvenile idiopathic arthritis, and to identify and quantify the potential role of plasma metabolites as mediators. Methods: Using summary-level data from genome-wide association studies, a two-sample Mendelian randomization was conducted involving 131 gut microbiota genus, 1,400 plasma metabolites, and juvenile idiopathic arthritis. Additionally, a two-step approach was employed to quantify the proportion of the effect of gut microbiota on juvenile idiopathic arthritis mediated by plasma metabolites. Effect estimation primarily utilized Inverse Variance Weighting, with further validation using Bayesian weighted Mendelian randomization. Results: In our MR analysis, a positive correlation was observed between Rikenellaceae and the risk of juvenile idiopathic arthritis, while Dorea showed a negative correlation with juvenile idiopathic arthritis risk. Mediation analysis indicated that Furaneol sulfate levels acted as a mediator between Dorea and juvenile idiopathic arthritis, with an indirect effect proportion of 19.94, 95% CI [8.86-31.03%]. Conclusion: Our study confirms a causal relationship between specific microbial genus and juvenile idiopathic arthritis, and computes the proportion of the effect mediated by plasma metabolites, offering novel insights for clinical interventions in juvenile idiopathic arthritis.

Linear optimal transport subspaces for point set classification.

Learning from point sets is an essential component in many computer vision and machine learning applications. Native, unordered, and permutation invariant set structure space is challenging to model, particularly for point set classification under spatial deformations. Here we propose a framework for classifying point sets experiencing certain types of spatial deformations, with a particular emphasis on datasets featuring affine deformations. Our approach employs the Linear Optimal Transport (LOT) transform to obtain a linear embedding of set-structured data. Utilizing the mathematical properties of the LOT transform, we demonstrate its capacity to accommodate variations in point sets by constructing a convex data space, effectively simplifying point set classification problems. Our method, which employs a nearest-subspace algorithm in the LOT space, demonstrates label efficiency, non-iterative behavior, and requires no hyper-parameter tuning. It achieves competitive accuracies compared to state-of-the-art methods across various point set classification tasks. Furthermore, our approach exhibits robustness in out-of-distribution scenarios where training and test distributions vary in terms of deformation magnitudes.

Risk analysis of air pollutants and types of anemia: a UK Biobank prospective cohort study.

Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.

Pentraxin 3 exacerbates psoriasiform dermatitis through regulation of macrophage polarization.

OBJECTIVE: To elucidate the mechanism of Pentraxin 3 (PTX3) in the pathogenesis of psoriasiform dermatitis using Ptx3-knockout (Ptx3-KO) background mice. METHODS: An Imiquimod (IMQ)-induced murine psoriatic model was created using Ptx3-KO (Ptx3-/-) and wild-type (Ptx3+/+) mice. Skin lesion severity and expression of inflammatory mediators (IL-6 and TNFα) were assessed using PASI score and ELISA, respectively. Cutaneous tissues from the two mice groups were subjected to histological analyses, including HE staining, Masson staining, and Immunohistochemistry (IHC). The PTX3, iNOS, COX2, and Arg1 expressions were quantified and compared between the two groups. We used RNA-seq to clarify the underlying mechanisms of the disease. Flow cytometry was used to analyze systemic Th17 cell differentiation and macrophage polarization. RESULT: The psoriatic region exhibited a higher PTX3 expression than the normal cutaneous area. Moreover, PTX3 was upregulated in HaCaT cells post-TNFα stimulation. Upon IMQ stimulation, Ptx3-/- mice displayed a lower degree of the psoriasiform dermatitis phenotype compared to Ptx3+/+ mice. Consistent with the RNA-seq results, further experiments confirmed that compared to the wild-type group, the PTX3-KO group exhibited a generally lower IL-6, TNFα, iNOS, and COX2 expression and a contrasting trend in macrophage polarization. However, no significant difference in Th17 cell activation was observed between the two groups. CONCLUSIONS: This study revealed that PTX3 was upregulated in psoriatic skin tissues and TNFα-stimulated HaCaT cells. We also discovered that PTX3 deficiency in mice ameliorated the psoriasiform dermatitis phenotype upon IMQ stimulation. Mechanistically, PTX3 exacerbates psoriasiform dermatitis by regulating macrophage polarization rather than Th17 cell differentiation.

Perfluorohexyloctane Ophthalmic Solution: A Review in Dry Eye Disease.

Perfluorohexyloctane ophthalmic solution (Miebo®) is a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane that is approved in the USA for the treatment of the signs and symptoms of dry eye disease (DED). DED is often linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution stabilizes the lipid layer of the tear film and inhibits tear evaporation by forming a monolayer at the air-liquid interface. In the phase III GOBI and MOJAVE trials in adults with DED associated with MGD, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks resulted in statistically significant and clinically meaningful improvements in the signs and symptoms of DED compared with hypotonic saline (0.6%). The agent was generally well tolerated, with most ocular adverse events being mild or moderate in severity. The efficacy and tolerability of perfluorohexyloctane ophthalmic solution was sustained for up to 52 weeks in an extension study (KALAHARI). As the first and currently the only prescription treatment approved in the USA directly addressing the pathophysiology of excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.

Dry eye disease (DED) is a common eye disorder caused by many factors. In most cases, DED is linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution (Miebo^®), a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane, is approved in the USA for the treatment of the signs and symptoms of DED. The agent stabilizes the lipid layer of the tear film and prevents the evaporation of tears by forming a layer on the surface of the tear film. In two phase III clinical trials in adults with MGD-associated DED, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks led to significant improvements in the signs and symptoms of DED when compared with hypotonic saline (0.6%). Perfluorohexyloctane ophthalmic solution was generally well tolerated, with most ocular adverse events being mild or moderate in severity. Thus, as the first and currently the only prescription treatment approved in the USA directly addressing excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.

Strain Engineering for Electrocatalytic Overall Water Splitting.

Strain engineering is a novel method that can achieve superior performance for different applications. The lattice strain can affect the performance of electrochemical catalysts by changing the binding energy between the surface-active sites and intermediates and can be affected by the thickness, surface defects and composition of the materials. In this review, we summarized the basic principle, characterization method, introduction strategy and application direction of lattice strain. The reactions on hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) are focused. Finally, the present challenges are summarized, and suggestions for the future development of lattice strain in electrocatalytic overall water splitting are put forward.

Single and mixed effects of multiple volatile organic compounds exposure on hematological parameters in the U.S. adult population.

BACKGROUND: Most research exploring the correlation between volatile organic compounds (VOCs) and hematological parameters have focused on single VOCs. Our study aimed to explore the single and combined effects of VOCs on hematological parameters through three statistical models. METHODS: Data from 4 cycles of the National Health and Nutrition Examination Survey (NHANES) were used in this study. The correlations between single exposure to 16 VOCs and hematological parameters in the general population were assessed by weighted multiple linear regression. Weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were used to explore the relationship between the combined important VOCs selected by the least absolute shrinkage and selection operator (LASSO) and hematological parameters, as well as the effects of smoking status on them. RESULTS: A total of 4089 adults were included in the study. We found that a variety of VOCs were significantly associated with hematological parameters. Among them, N-acetyl-S-(benzyl)-l-cysteine (BMA) was significantly negatively correlated with white blood cell (WBC), red blood cell (RBC), lymphocyte, and neutrophil counts. N-acetyl-S-(3-hydroxypropyl-1-methyl)-l-cysteine (HPMMA) was significantly positively correlated with WBC, monocyte, lymphocyte, and neutrophil counts. In the WQS analysis, the WQS index of the VOCs mixtures was positively correlated with WBC (ß: 0.031; P < 0.001), monocyte (0.023; P = 0.021), and neutrophil (0.040; P = 0.001) counts, while negatively associated with RBC (-0.013; P < 0.001) counts. The BKMR model revealed that combined exposure to VOCs levels ≥70th percentile was significantly associated with lower RBC counts, and BMA was identified as the dominant contributor. Smoking significantly influenced the relationship between VOCs and hematological parameters. CONCLUSIONS: Our study indicated the effects of single and overall VOCs exposure on hematological parameters and suggested the hematotoxicity as well as pro-inflammatory effects of VOCs, which had strong public health implications for reducing the potential health hazards of VOCs exposure to the hematologic system.

End-to-End Signal Classification in Signed Cumulative Distribution Transform Space.

This paper presents a new end-to-end signal classification method using the signed cumulative distribution transform (SCDT). We adopt a transport generative model to define the classification problem. We then make use of mathematical properties of the SCDT to render the problem easier in transform domain, and solve for the class of an unknown sample using a nearest local subspace (NLS) search algorithm in SCDT domain. Experiments show that the proposed method provides high accuracy classification results while being computationally cheap, data efficient, and robust to out-of-distribution samples with respect to the existing end-to-end classification methods. The implementation of the proposed method in Python language is integrated as a part of the software package PyTransKit.

Three-dimensional visualization of thyroid ultrasound images based on multi-scale features fusion and hierarchical attention.

BACKGROUND: Ultrasound three-dimensional visualization, a cutting-edge technology in medical imaging, enhances diagnostic accuracy by providing a more comprehensive and readable portrayal of anatomical structures compared to traditional two-dimensional ultrasound. Crucial to this visualization is the segmentation of multiple targets. However, challenges like noise interference, inaccurate boundaries, and difficulties in segmenting small structures exist in the multi-target segmentation of ultrasound images. This study, using neck ultrasound images, concentrates on researching multi-target segmentation methods for the thyroid and surrounding tissues. METHOD: We improved the Unet++ to propose PA-Unet++ to enhance the multi-target segmentation accuracy of the thyroid and its surrounding tissues by addressing ultrasound noise interference. This involves integrating multi-scale feature information using a pyramid pooling module to facilitate segmentation of structures of various sizes. Additionally, an attention gate mechanism is applied to each decoding layer to progressively highlight target tissues and suppress the impact of background pixels. RESULTS: Video data obtained from 2D ultrasound thyroid serial scans served as the dataset for this paper.4600 images containing 23,000 annotated regions were divided into training and test sets at a ratio of 9:1, the results showed that: compared with the results of U-net++, the Dice of our model increased from 78.78% to 81.88% (+ 3.10%), the mIOU increased from 73.44% to 80.35% (+ 6.91%), and the PA index increased from 92.95% to 94.79% (+ 1.84%). CONCLUSIONS: Accurate segmentation is fundamental for various clinical applications, including disease diagnosis, treatment planning, and monitoring. This study will have a positive impact on the improvement of 3D visualization capabilities and clinical decision-making and research in the context of ultrasound image.

Biomimetic Dual-Network Collagen Fibers with Porous and Mechanical Cues Reconstruct Neural Stem Cell Niche via AKT/YAP Mechanotransduction after Spinal Cord Injury.

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.

Aminopeptidase O Protein mediates the association between Lachnospiraceae and appendicular lean mass.

Objective: Investigating the causal relationship between Lachnospiraceae and Appendicular lean mass (ALM) and identifying and quantifying the role of Aminopeptidase O Protein (AOPEP) as a potential mediator. Methods: The summary statistics data of gut microbiota composition from the largest available genome-wide association study (GWAS) meta-analysis conducted by the MiBioGen Consortium (n = 13,266). Appendicular lean mass data were obtained from the UK-Biobank (n = 450,243). We conducted bidirectional two-sample Mendelian randomization (MR) analysis using summary-level data from GWAS to investigate the causal relationship between Lachnospiraceae and ALM. Additionally, we employed a drug-targeted MR approach to assess the causal relationship between AOPEP and ALM. Finally, a two-step MR was employed to quantitatively estimate the proportion of the effect of Lachnospiraceae on ALM that is mediated by AOPEP. Cochran's Q statistic was used to quantify heterogeneity among instrumental variable estimates. Results: In the MR analysis, it was found that an increase in genetically predicted Lachnospiraceae [OR = 1.031, 95% CI (1.011-1.051), P = 0.002] is associated with an increase in ALM. There is no strong evidence to suggest that genetically predicted ALM has an impact on Lachnospiraceae genus [OR = 1.437, 95% CI (0.785-2.269), P = 0.239]. The proportion of genetically predicted Lachnospiraceae mediated by AOPEP was 34.2% [95% CI (1.3%-67.1%)]. Conclusion: Our research reveals that increasing Lachnospiraceae abundance in the gut can directly enhance limb muscle mass and concurrently suppress AOPEP, consequently mitigating limb muscle loss. This supports the potential therapeutic modulation of gut microbiota for sarcopenia. Interventions such as drug treatments or microbiota transplantation, aimed at elevating Lachnospiraceae abundance and AOPEP inhibition, synergistically improve sarcopenia in the elderly, thereby enhancing the overall quality of life for older individuals.

[Mechanism about LMP1 of EB Virus Promoting Plasma Blast Differentiation of DLBCL Cell via mTORC1].

OBJECTIVE: To investigate possible mechanism on protien LMP1 expressed by EBV inducing plasmablast differentiation of DLBCL cell via the mTORC1 pathway. METHODS: The expression levels of LMP1 protein, CD38 and the phosphorylation levels of p70S6K in EBV+ and EBV- DLBCL cell lines were detected by Western blot. Cell lines overexpressing LMP1 gene stablely were constructed and LMP1 gene was silenced by RNAi. The expression of LMP1 gene was verified by RT-qPCR. The expression levels of LMP1 and CD38 and the phosphorylation levels of p70S6K in each group were detected by Western blot. RESULTS: Compared with EBV-DLBCL cells, the expression of LMP1 was detected on EBV +DLBCL cells (P =0.0008), EBV +DLBCL cells had higher phosphorylation levels of p70S6K (P =0.0072) and expression levels of CD38(P =0.0091). Compared with vector group, the cells of LMP1OE group had higher expression levels of LMP1 and CD38 (P =0.0353; P <0.0001), meanwhile molecular p70S6K was phosphorylated much more(P =0.0065); expression of LMP1 mRNA was verified(P <0.0001). Compared with si-NC group, expression level of LMP1 protein(P =0.0129) was not detected and phosphorylated p70S6K disappeared of LMP1KO group (P =0.0228); meanwhile, expression of CD38 decreased,although there was no significant difference (P =0.2377). CONCLUSION: LMP1 promotes DLBCL cells plasmablast differentiation via activating mTORC1 signal pathway.

Segmentation of pelvic structures in T2 MRI via MR-to-CT synthesis.

Segmentation of multiple pelvic structures in MRI volumes is a prerequisite for many clinical applications, such as sarcopenia assessment, bone density measurement, and muscle-to-fat volume ratio estimation. While many CT-specific datasets and automated CT-based multi-structure pelvis segmentation methods exist, there are few MRI-specific multi-structure segmentation methods in literature. In this pilot work, we propose a lightweight and annotation-free pipeline to synthetically translate T2 MRI volumes of the pelvis to CT, and subsequently leverage an existing CT-only tool called TotalSegmentator to segment 8 pelvic structures in the generated CT volumes. The predicted masks were then mapped back to the original MR volumes as segmentation masks. We compared the predicted masks against the expert annotations of the public TCGA-UCEC dataset and an internal dataset. Experiments demonstrated that the proposed pipeline achieved Dice measures ≥65% for 8 pelvic structures in T2 MRI. The proposed pipeline is an alternative method to obtain multi-organ and structure segmentations without being encumbered by time-consuming manual annotations. By exploiting the significant research progress in CTs, it is possible to extend the proposed pipeline to other MRI sequences in principle. Our research bridges the chasm between the current CT-based multi-structure segmentation and MRI-based segmentation. The manually segmented structures in the TCGA-UCEC dataset are publicly available.

Electronic Fingerprint of the Protonated Imidazole Dimer Probed by X-ray Absorption Spectroscopy.

Protons in low-barrier superstrong hydrogen bonds are typically delocalized between two electronegative atoms. Conventional methods to characterize such superstrong hydrogen bonds are vibrational spectroscopy and diffraction techniques. We introduce soft X-ray spectroscopy to uncover the electronic fingerprints for proton sharing in the protonated imidazole dimer, a prototypical building block enabling effective proton transport in biology and high-temperature fuel cells. Using nitrogen core excitations as a sensitive probe for the protonation status, we identify the X-ray signature of a shared proton in the solvated imidazole dimer in a combined experimental and theoretical approach. The degree of proton sharing is examined as a function of structural variations that modify the shape of the low-barrier potential in the superstrong hydrogen bond. We conclude by showing how the sensitivity to the quantum distribution of proton motion in the double-well potential is reflected in the spectral signature of the shared proton.

Deciphering the dynamics and driving mechanisms of high-risk antibiotic resistome in size-fractionated bacterial community during drinking water chlorination via metagenomic analysis.

To reveal the impact of chlorination on the high-risk resistome in size-fractionated bacterial community, we employed metagenomic approaches to decipher dynamics of high-risk antibiotic resistance genes (ARGs) and driving mechanisms in the free-living and particle-associated fractions within a full-scale drinking water treatment system. Our results revealed that chlorination significantly increased the relative abundance of high-risk ARGs in the free-living fraction to 0.33 ± 0.005 copies/cell (cpc), bacitracin and chloramphenicol resistance types were major contributors. Furthermore, chlorination significantly increased the relative abundance of mobile genetic elements (MGEs) in the free-living fraction, while decreasing it in the particle-associated fraction. During chlorination, size-fractionated bacterial communities varied considerably. Multiple statistical analyses highlighted the pivotal role of the bacterial community in altering high-risk ARGs in both the free-living and particle-associated fractions, while MGEs had a more pronounced impact on high-risk ARGs in the free-living fraction. Specifically, the enrichment of pathogenic hosts, such as Comamonas and Pseudomonas, led to an increase in the abundance of high-risk ARGs. Concurrently, MGEs exhibited significant correlations with high-risk ARGs, indicating the potential of horizontal transfer of high-risk ARGs. These findings provide novel insights for mitigating antibiotic resistance risk by considering different bacterial fractions and respective risk ranks in drinking water.

Application of Solvent-Assisted Dual-Network Hydrogel in Water-Based Drilling Fluid for Lost Circulation Treatment in Fractured Formation.

During oil and gas well construction, lost circulation caused substantial nonoperation time and extra costs, and hydrogel, resilient and environmentally friendly, was one of the major types of material for lost circulation treatment. To migrate the weak bonding and hydrothermal degradation of conventional single network hydrogels, dual network (DN) hydrogel was prepared and immersed in solvents of polyethylene glycol (PEG), ethylene glycol, and glycerol. The swelling of DN gels at different temperatures was studied with water content and swelling rate tests, and the gel structural and morphology was characterized with attenuated total reflectance infrared spectroscopy (ATR-IR) and scanning electron microscopy test. Then, the compression test and fracture plugging performance test were conducted to study the strength of the gel. The results show that compared to those in ethylene glycol and glycerin, DN gel after immersion in PEG (DN-PEG) exhibits greater compression strength and better plugging performance even at high temperatures. The compression strength of DN-PEG was twice that of DN hydrogel before immersion, and its fracture plug breaking pressure can reach over 10.0 MPa. After undergoing hydrothermal treatment at 90 °C, the compression strength of the DN-PEG was nearly 20 times that of the DN hydrogel, and the fracture plug breaking pressure was still 2.81 MPa. According to ATR-IR spectroscopy, as the molecular weight of the solvent increases, more hydroxyl groups in the PEG have better ability to bind with hydrogen bonds, which greatly inhibits the swelling and polymer chain breakage, thereby reducing hydrothermal degradation in the strength of the dual-network hydrogel. Our work proposed an effective method to reduce the degradation of hydrogel in water at high temperature, and the prepared DN-PEG hydrogel was a promising material for lost circulation treatments in fractured formation.

Unveiling protein corona composition: predicting with resampling embedding and machine learning.

Biomaterials with surface nanostructures effectively enhance protein secretion and stimulate tissue regeneration. When nanoparticles (NPs) enter the living system, they quickly interact with proteins in the body fluid, forming the protein corona (PC). The accurate prediction of the PC composition is critical for analyzing the osteoinductivity of biomaterials and guiding the reverse design of NPs. However, achieving accurate predictions remains a significant challenge. Although several machine learning (ML) models like Random Forest (RF) have been used for PC prediction, they often fail to consider the extreme values in the abundance region of PC absorption and struggle to improve accuracy due to the imbalanced data distribution. In this study, resampling embedding was introduced to resolve the issue of imbalanced distribution in PC data. Various ML models were evaluated, and RF model was finally used for prediction, and good correlation coefficient (R2) and root-mean-square deviation (RMSE) values were obtained. Our ablation experiments demonstrated that the proposed method achieved an R2 of 0.68, indicating an improvement of approximately 10%, and an RMSE of 0.90, representing a reduction of approximately 10%. Furthermore, through the verification of label-free quantification of four NPs: hydroxyapatite (HA), titanium dioxide (TiO2), silicon dioxide (SiO2) and silver (Ag), and we achieved a prediction performance with an R2 value >0.70 using Random Oversampling. Additionally, the feature analysis revealed that the composition of the PC is most significantly influenced by the incubation plasma concentration, PDI and surface modification.