Electrochemical Detection of Myoglobin Using an Ultrasensitive Label-free Sensor Derived from Cubic-ZIF67@Au-rGOF-NH2 Composite of MOF and GOF.

Markers of myocardial injury, such as myoglobin (Mb), are substances swiftly released into the peripheral bloodstream upon myocardial cell injury or altered cardiac activity. During the onset of acute myocardial infarction, patients experience a significant surge in serum Mb levels. Given this, precise detection of Mb is essential, necessitating the development of innovative assays to optimize detection capabilities. This study introduces the synthesis of a three-dimensional hierarchical nanocomposite, Cubic-ZIF67@Au-rGOF-NH2, utilizing aminated reduced graphene oxide and zeolite imidazolium ester framework-67 (ZIF67) as foundational structures. Notably, this novel material, applied in a label-free electrochemical immunosensor, presents a groundbreaking approach for detecting myocardial injury markers. Experimental outcomes revealed ZIF67 and AuNPs exhibit enhanced affinity and growth on the 3D-rGOF-NH2 matrix, thus amplifying electrical conductivity while preserving the inherent electrochemical attributes of ZIF67. As a result, the Cubic-ZIF67@Au-rGOF-NH2 label-free electrochemical immunosensor exhibited a broad detection range and high sensitivity for Mb. The derived standard curve was ΔIp=16.67552lgC+275.245 (R=0.993) with a detection threshold of 3.47 fg/ml. Moreover, recoveries of standards spiked into samples ranged between 96.3% to 108.7%. Importantly, the devised immunosensor retained notable selectivity against non-target proteins, proving its potential clinical utility based on exemplary sample analysis performance.

Synthesis of ß,ß-Dithioketones by Merging C-C and C-S Bond Cleavage in [1 + 1 + 1 + 1 + 1 + 1] Annulation.

An unconventional [1 + 1 + 1 + 1 + 1 + 1] annulation process was developed for the construction of ß,ß-dithioketones by merging C-C and C-S bond cleavage. In this reaction, rongalite concurrently served as triple C1 units, dual sulfur(II) synthons, and a reductant for the first time. Mechanism investigation indicated that the reaction involved the self-mediated valence state change of rongalite. By performing this step-economical method, the challenging construction of C5-substituted 1,3-dithiane can be achieved under mild and simple conditions.

Biochar reduces antibiotic transport by altering soil hydrology and enhancing antibiotic sorption.

The performance of biochar (BC) in reducing the transport of antibiotics under field conditions has not been sufficiently explored. In repacked sloping boxes of a calcareous soil, the effects of different BC treatments on the discharge of three relatively weakly sorbing antibiotics (sulfadiazine, sulfamethazine, and florfenicol) via runoff and drainage were monitored for three natural rain events. Surface application of 1 % BC (1 %BC-SA) led to the most effective reduction in runoff discharge of the two sulfonamide antibiotics, which can be partly ascribed to the enhanced water infiltration. The construction of 5 % BC amended permeable reactive wall (5 %BC-PRW) at the lower end of soil box was more effective than the 1 %BC-SA treatment in reducing the leaching of the most weakly sorbing antibiotic (florfenicol), which can be mainly ascribed to the much higher plant available and drainable water contents in the 5 %BC-PRW soil than in the unamended soil. The results of this study highlight the importance of BC's ability to regulate flow pattern by modifying soil hydraulic properties, which can make a significant contribution to the achieved reduction in the transport of antibiotics offsite or to groundwater.

Predicting therapeutic response to neoadjuvant immunotherapy based on an integration model in resectable stage IIIA (N2) non-small cell lung cancer.

OBJECTIVE: Accurately predicting response during neoadjuvant chemoimmunotherapy for resectable non-small cell lung cancer (NSCLC) remains clinically challenging. In this study, we investigate the effectiveness of blood-based tumor mutational burden (bTMB) and a deep learning (DL) model in predicting major pathologic response (MPR) and survival from a phase II trial. METHODS: Blood samples were prospectively collected from 45 stage IIIA (N2) NSCLC patients undergoing neoadjuvant chemoimmunotherapy. An integrated model, combining the CT-based DL score, bTMB, and clinical factors, was developed to predict tumor response to neoadjuvant chemoimmunotherapy. RESULTS: At baseline, bTMB were detected in 77.8% (35 of 45) of patients. Baseline bTMB ≥11 Muts/Mb was associated with significantly higher MPR rates (77.8% vs. 38.5%, p = 0.042), and longer disease-free survival (DFS, p = 0.043), but not overall survival (p = 0.131), compared to bTMB < 11 Muts/Mb in 35 patients with bTMB available. The developed DL model achieved an area under the curve (AUC) of 0.703 in all patients. Importantly, the predictive performance of the integrated model improved to an AUC of 0.820 when combining the DL score with bTMB and clinical factors. Baseline circulating tumor DNA (ctDNA) status was not associated with pathological response and survival. Compared to ctDNA residual, ctDNA clearance before surgery was associated with significantly higher MPR rates (88.2% vs. 11.1%, p < 0.001) and improved DFS (p = 0.010). CONCLUSIONS: The integrated model shows promise as a predictor of tumor response to neoadjuvant chemoimmunotherapy. Serial ctDNA dynamics provide a reliable tool for monitoring tumor response.

A case of iatrogenic acute spinal cord injury with tetraplegia following thyroid surgery.

AIM: Iatrogenic acute spinal cord injury with tetraplegia is a serious consequence of non-spinal surgery.We report a case of acute spinal cord injury with tetraplegia after thyroid surgery. METHOD: The patient was pathologically diagnosed with papillary carcinoma, underwent left thyroidectomy, and developed tetraplegia after surgery. RESULT: The patient was diagnosed with acute spinal cord injury with tetraplegia and cured after anti-inflammatory and dehydrating treatment. CONCLUSION: Iatrogenic spinal cord injuries after elective non-spinal surgery can have catastrophic consequences, and clinicians must be alert to this possibility in clinical practice.

Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.

Metabolic crosstalk of the major nutrients glucose, amino acids and fatty acids (FAs) ensures systemic metabolic homeostasis. The coordination between the supply of glucose and FAs to meet various physiological demands is especially important as improper nutrient levels lead to metabolic disorders, such as diabetes and metabolic dysfunction-associated steatohepatitis (MASH). In response to the oscillations in blood glucose levels, lipolysis is thought to be mainly regulated hormonally to control FA liberation from lipid droplets by insulin, catecholamine and glucagon. However, whether general cell-intrinsic mechanisms exist to directly modulate lipolysis via glucose sensing remains largely unknown. Here we report the identification of such an intrinsic mechanism, which involves Golgi PtdIns4P-mediated regulation of adipose triglyceride lipase (ATGL)-driven lipolysis via intracellular glucose sensing. Mechanistically, depletion of intracellular glucose results in lower Golgi PtdIns4P levels, and thus reduced assembly of the E3 ligase complex CUL7FBXW8 in the Golgi apparatus. Decreased levels of the E3 ligase complex lead to reduced polyubiquitylation of ATGL in the Golgi and enhancement of ATGL-driven lipolysis. This cell-intrinsic mechanism regulates both the pool of intracellular FAs and their extracellular release to meet physiological demands during fasting and glucose deprivation. Moreover, genetic and pharmacological manipulation of the Golgi PtdIns4P-CUL7FBXW8-ATGL axis in mouse models of simple hepatic steatosis and MASH, as well as during ex vivo perfusion of a human steatotic liver graft leads to the amelioration of steatosis, suggesting that this pathway might be a promising target for metabolic dysfunction-associated steatotic liver disease and possibly MASH.

Prediction of embryo euploidy and pregnancy outcome by blastocyst morphology and development speed for women receiving single embryo transfer.

BACKGROUND: Selection of high-quality blastocysts is the most important factor determining the success of assisted reproductive technology. The objective of this study is to assess the values of blastocyst morphological quality and development speed for predicting euploidy and clinical pregnancy outcome. METHODS: A total of 155 preimplantation genetic testing cycles including 959 blastocysts and 154 euploid blastocyst transfer cycles conducted between January 2018 and December 2019 were retrospectively analysed. The associations of blastocyst morphological quality and development speed (D) with chromosomal status, clinical pregnancy rate, early miscarriage rate, and ongoing pregnancy rate were evaluated by univariate and multivariate regression. RESULTS: The euploidy rate of development speed D5 blastocysts was significantly greater than that of D6 blastocysts (61.4% vs. 38.1%, P < 0.001), and the euploid rate of morphologically high-grade blastocysts was significantly greater than that of non-high-grade blastocysts. Development speed D5 (OR = 1.6, 95% CI 1.2-2.2, P = 0.02) and high-grade morphology (OR = 2.1, 95% CI 1.5-2.9, P = 0.01) were independent predictors of euploidy. The ongoing pregnancy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (62.3% vs. 43.8%, P = 0.04). Transfer of euploid blastocysts with high-grade morphology resulted in a greater ongoing pregnancy rate than transfer of non-high-grade euploid blastocysts (60.7% vs. 43.2%, P = 0.049). Alternatively, D6 development speed was an independent risk factor for early pregnancy loss after euploid blastocyst transfer. Multivariate regression analysis adjusting for confounding factors identified maternal age, blastocyst development speed, and blastocyst morphological grade as independent predictors of euploidy but not of clinical pregnancy. CONCLUSION: The recommended sequence of embryo transfer based on the present study is D5 high-grade > D6 high-grade > D5 non-high-grade > D6 non-high-grade.

Assisted reproductive technology physicians are actively exploring methods to improve the accuracy of embryo selection for successful pregnancy. We evaluated the associations of embryo morphological grade and development speed with chromosomal status and clinical outcome for couples without a history of infertility, in vitro fertilisation failure, or recurrent miscarriage receiving euploid embryo transfer. Blastocysts from females younger than 35 years, of high morphological grade, and demonstrating faster development speed were most likely to be euploid (least likely to have chromosomal abnormalities). Alternatively, patients implanted with slower developing euploid blastocysts were at higher risk of early pregnancy loss. To maximise the probability of implanting euploid embryos and minimise the risk of pregnancy loss, the selection order of embryo transferred should be based on embryo development speed followed by morphological grades.

Nitrogen fertilization modulates rice phyllosphere functional genes and pathogens through fungal communities.

The phyllosphere is a vital yet often neglected habitat hosting diverse microorganisms with various functions. However, studies regarding how the composition and functions of the phyllosphere microbiome respond to agricultural practices, like nitrogen fertilization, are limited. This study investigated the effects of long-term nitrogen fertilization with different levels (CK, N90, N210, N330) on the functional genes and pathogens of the rice phyllosphere microbiome. Results showed that the relative abundance of many microbial functional genes in the rice phyllosphere was significantly affected by nitrogen fertilization, especially those involved in C fixation and denitrification genes. Different nitrogen fertilization levels have greater effects on fungal communities than bacteria communities in the rice phyllosphere, and network analysis and structural equation models further elucidate that fungal communities not only changed bacterial-fungal inter-kingdom interactions in the phyllosphere but also contributed to the variation of biogeochemical cycle potential. Besides, the moderate nitrogen fertilization level (N210) was associated with an enrichment of beneficial microbes in the phyllosphere, while also resulting in the lowest abundance of pathogenic fungi (1.14 %). In contrast, the highest abundance of pathogenic fungi (1.64 %) was observed in the highest nitrogen fertilization level (N330). This enrichment of pathogen due to high nitrogen level was also regulated by the fungal communities, as revealed through SEM analysis. Together, we demonstrated that the phyllosphere fungal communities were more sensitive to the nitrogen fertilization levels and played a crucial role in influencing phyllosphere functional profiles including element cycling potential and pathogen abundance. This study expands our knowledge regarding the role of phyllosphere fungal communities in modulating the element cycling and plant health in sustainable agriculture.

Porcine HERC6 acts as major E3 ligase for ISGylation and is auto-ISGylated for effective ISGylation in porcine.

Interferon-stimulated gene product 15 (ISG15) can be conjugated to substrates through ISGylation. Currently, the E3 ligase for porcine ISGylation remains unclear. Here, we identified porcine HERC5 and HERC6 (pHERC5/6) as ISGylation E3 ligases with pHERC6 acting as a major one by reconstitution of porcine ISGylation system in HEK-293 T cell via co-transfecting E1, E2 and porcine ISG15(pISG15) genes. Meanwhile, our data demonstrated that co-transfection of pISG15 and pHERC5/6 was sufficient to confer ISGylation, suggesting E1 and E2 of ISGylation are interchangeable between human and porcine. Using an immunoprecipitation based ISGylation analysis, our data revealed pHERC6 was a substrate for ISGylation and confirmed that K707 and K993 of pHERC6 were auto-ISGylation sites. Mutation of these sites reduced pHERC6 half-life and inhibited ISGylation, suggesting that auto-ISGylation of pHERC6 was required for effective ISGylation. Conversely, sustained ISGylation induced by overexpression of pISG15 and pHERC6 could be inhibited by a well-defined porcine ISGylation antagonist, the ovarian tumor (OTU) protease domain of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-nsp2 and PRRSV-nsp1ß, further indicating such method could be used for identification of virus-encoded ISG15 antagonist. In conclusion, our study contributes new insights towards porcine ISGylation system and provides a novel tool for screening viral-encoded ISG15 antagonist.

Ultrasensitive and label-free electrochemical immunosensor for the detection of the ovarian cancer biomarker CA125 based on CuCo-ONSs@AuNPs nanocomposites.

Cancer antigen 125 (CA125) is pivotal as a tumor marker in early ovarian cancer prevention and diagnosis. In this work, we introduced an ultrasensitive label-free electrochemical immunosensor tailored for CA125 detection, leveraging nanogold-functionalized copper-cobalt oxide nanosheets (CuCo-ONSs@AuNPs) as nanocomposites. For the inaugural application, copper-cobalt oxide nanosheets delivered the requisite DPV electrochemical response for the immunosensors. Their large specific surface area and commendable electrical conductivity amplify electron transfer and enable significant gold nanoparticle loading. Concurrently, AuNPs offer a plethora of active sites, facilitating easy immobilization of biomolecules via the bond between amino groups and AuNPs. We employed scanning electron microscopy, transmission electron microscopy, and x-ray photoelectron spectroscopy to characterize the nanomaterials' surface morphology and elemental composition. The electrochemical sensor response signals were ascertained using differential pulse voltammetry. Under optimal conditions, the immunosensor exhibited a linear detection range from 1×10-7 U/mL to 1×10-3 U/mL and a detection limit of 3.9×10-8 U/mL (S/N=3). The proposed label-free electrochemical immunosensor furnishes a straightforward, dependable, and sensitive approach for CA125 quantification and stands as a promising method for clinical detection of other tumor markers.

A meta-analysis on the efficacy of endoscopic ultrasonography for treatment of pancreatic cancer.

OBJECTIVE: This study aimed to systematically evaluate the efficacy and safety of Endoscopic Ultrasonography (EUS) for the treatment of pancreatic cancer. METHODS: The PubMed, Embase, Web of Science, and Google Scholar databases were searched from the inception of the databases to June 2022. RevMan 5.3.0 software was utilized for data analysis. In total, 13 self-descriptive studies, which enrolled 382 patients, were finally included. RESULTS: It was revealed that EUS for the treatment of pancreatic cancer exhibited a lower incidence of adverse reactions (Relative Risk Ration [RR = 0.23], 95 % Confidence interval [95 % CI 0.23-0.23]), a higher success rate (RR = 0.90, 95 % CI 0.90-0.90), and a low failure rate (RR = 0.06, 95 % CI 0.06-0.06). Moreover, EUS-guided Celiac Plexus Neurolysis (EUS-CPN) not only significantly relieved pancreatic cancer patients' pain (RR = 0.83, 95 % CI 0.83-0.83), but also significantly eliminated pain in some patients (RR = 0.09, 95 % CI 0.09-0.09). The effects of EUS on pancreatic cancer treatment were satisfactory, and few adverse reactions were found. CONCLUSION: Owing to the restricted sample size in this meta-analysis, primarily consisting of descriptive studies, it was imperative to conduct more rigorously designed, multi-center, long-term follow-up, larger sample, and Randomized Controlled Trials (RCTs) to validate the findings.

Characterization of in vitro viral neutralization targets of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) in alveolar macrophage and evaluation of protection potential against HP-PRRSV challenged based on combination of HP-PRRSV-structure proteins in vitro.

Porcine reproductive and respiratory syndrome virus (PRRSV) poses a significant threat to the global pork industry, resulting in substantial economic losses. Current control measures rely on modified live virus (MLV) vaccines with safety concerns. However, the lack of consensus on protective PRRSV antigens is impeding the development of effective and safety subunit vaccines. In this study, we conducted in vitro virus neutralization (VN) assays in MARC-145 and CRL-2843CD163/CD169 cell lines and primary porcine alveolar macrophages (PAMs) to systemically identify PRRSV structural proteins (SPs) recognized by virus-neutralizing antibodies in hyperimmune serum collected from piglets infected with highly pathogenic PRRSV (HP-PRRSV). Additionally, piglets immunized with different combinations of recombinant PRRSV-SPs were challenged with HP-PRRSV to evaluate their in vivo protection potential. Intriguingly, different in vitro VN activities of serum antibodies elicited by each PRRSV SP were observed depending on the cell type used in the VN assay. Notably, antibodies specific for GP3, GP4, and M exhibited highest in vitro VN activities in PAMs, correlating with complete protection (100% survival) against HP-PRRSV challenge in vivo after immunization of piglets with combination of GP3, GP4, M and N (GP3/GP4/M/N). Further analysis of lung pathology, weight gain, and viremia post-challenge revealed that the combination of GP3/GP4/M/N provided superior protective efficacy against severe infection. These findings underscore the potential of this SP combination to serve as an effective PRRSV subunit vaccine, marking a significant advancement in pork industry disease management.

Spread Through Air Spaces in Residual Tumor Classification for Clinical IA Lung Adenocarcinoma.

BACKGROUND: We aimed to validate the prognostic implication of uncertain resection, R(un), proposed by International Association for the Study of Lung Cancer (IASLC) and evaluate the prognostic value of spread through air spaces (STAS) in reclassifying the R classification among patients with lung adenocarcinoma after segmentectomy. METHODS: We enrolled 1007 patients who underwent segmentectomy for c-stage IA lung adenocarcinoma between 2014 and 2017. Recurrence-free survival (RFS) and overall survival (OS) were compared to evaluate the prognostic value of IASLC-R(un) and STAS. Whether STAS would skip into complementary lobectomy was evaluated in a prospective cohort. RESULTS: The current IASLC-R(un) failed to significantly stratify the RFS (P = .078) in segmentectomy, and STAS was a stronger risk factor of poor prognosis for both RFS and OS (P < .001). Moreover, the presence of STAS was associated with increased locoregional recurrence in patients undergoing segmentectomy (P < .001) but not in those treated with lobectomy (P = .187), indicating that only STAS-positive segmentectomy was consistent with the concept of R(un) in relapse pattern. After reclassifying STAS-positive segmentectomy into the R(un) category, the proposed R(un) showed an improvement in prognosis stratification. In addition, 2 of 30 patients (6.2%) in the prospective cohort who underwent initial segmentectomy and complementary lobectomy had STAS clusters in the complementary lobectomy specimens. CONCLUSIONS: Unfavorable prognosis, relapse patterns consistent with R(un), and pathologic verification that saltatory spread of STAS observed in complementary lobectomy specimens supported reclassifying STAS-positive segmentectomy as R(un). STAS is a critical concern for the surgical completeness evaluation after segmentectomy.

Psychometric evaluation of the Chinese version of the fear of pregnancy scale: a translation and validation study.

Introduction: Many women experience fear toward pregnancy, which can impact their desire to have children and the national birth rate. Thus, assessing women's fear of pregnancy is of great importance. However, there is currently no specialized tool for assessing women's fear of pregnancy in China. The purpose of this study is to translate the Fear of Pregnancy Scale into Chinese and test its reliability and validity among women of childbearing age. Methods: Using convenience sampling combined with a snowballing method, a cross-sectional survey was conducted on 886 women of childbearing age in two cities in China. The translation was strictly carried out according to the Brislin model. Item analysis, validity analysis, and reliability analysis were employed for psychometric assessment. Results: The Chinese version of the Fear of Pregnancy Scale comprises 28 items. Exploratory factor analysis extracted four factors with a cumulative variance contribution rate of 72.578%. Confirmatory factor analysis showed: NFI = 0.956, CFI = 0.986, GFI = 0.927, IFI = 0.986, TLI = 0.985, RMSEA = 0.032, and χ2/df = 1.444. The scale's Cronbach's α coefficient is 0.957, split-half reliability is 0.840, and test-retest reliability is 0.932. Conclusion: The Chinese version of the Fear of Pregnancy Scale possesses robust psychometric properties and can assess the degree of pregnancy fear among Chinese women of childbearing age. It provides a reference for formulating relevant policies in the prenatal care service system and implementing targeted intervention measures.

Granulomatosis With Polyangiitis of Spinal Dura Presenting With "Bottle Brush Sign" on 18 F-FDG PET/CT.

ABSTRACT: A 72-year-old man with fever and weakness in both lower limbs underwent thoracolumbar MRI and 18 F-FDG PET/CT. The PET/CT scan revealed diffused FDG uptake along the spinal dura mater from T7 to S2 level like a "bottle brush." Pathologic examination after biopsy of spinal canal lesions manifested granulomatous inflammation. The blood test showed cytoplasmic antineutrophil cytoplasmic antibody (ANCA) and myeloperoxidase-ANCAs were positive, whereas the perinuclear ANCA was negative. Eventually, he was diagnosed with granulomatosis with polyangiitis.

Extracellular vesicles incorporating retrovirus-like capsids for the enhanced packaging and systemic delivery of mRNA into neurons.

The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-stabilizing Arc 5'-untranslated-region RNA elements. These engineered EVs inherit endothelial adhesion molecules from donor leukocytes, recruit endogenous enveloping proteins to their surface, cross the BBB, and enter the neurons in neuro-inflammatory sites. Produced from self-derived donor leukocytes, the EVs are immunologically inert, and enhanced the neuronal uptake of the packaged mRNA in a mouse model of low-grade chronic neuro-inflammation.

Chidamide and orelabrutinib synergistically induce cell cycle arrest and apoptosis in diffuse large B-cell lymphoma by regulating the PI3K/AKT/mTOR pathway.

OBJECTIVE: The initial therapeutic approach for diffuse large B-cell lymphoma (DLBCL) entails a rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen. However, 40% of patients exhibit suboptimal responses, with some experiencing relapse and refractory conditions. This study aimed to explore novel therapeutic strategies and elucidate their underlying mechanisms in DLBCL. METHODS: Bioinformatics techniques were employed to scrutinize correlations between the HDAC1, HDAC2, HDAC3, HDAC10, BTK, MYC, TP53, and BCL2 genes in DLBCL. In vitro experiments were conducted using DB and SU-DHL-4 cells treated with chidamide, orelabrutinib, and a combination of both. Cell viability was assessed by cell counting kit-8. Cell apoptosis and the cell cycle were determined using flow cytometry. Reactive oxygen species (ROS) production and mitochondrial function were assessed through ROS and JC-1 staining. RNA sequencing and western blot analyses were conducted to elucidate the molecular mechanisms underlying the combined action of chidamide and orelabrutinib in DLBCL cells. RESULTS: This investigation revealed markedly enhanced antiproliferative effects when chidamide was combined with orelabrutinib. Compusyn software analysis indicated a synergistic effect of chidamide and orelabrutinib in inhibiting DLBCL cell proliferation, with a combination index (CI) < 1. This synergy further manifested as augmented cell cycle arrest, apoptosis induction, the downregulation of cell cycle-associated and antiapoptotic proteins, and the upregulation of proapoptotic proteins. Furthermore, the western blot and RNA-Seq findings suggested that combining chidamide and orelabrutinib modulated the PI3K/AKT/mTOR signaling pathway, thereby promoting DLBCL cell cycle arrest and apoptosis. CONCLUSION: The findings of this study provide a compelling justification for the clinical utilization of chidamide and orelabrutinib to treat relapsed/refractory DLBCL.

Incorporation of the lepidic component as an additional pathological T descriptor for non-small cell lung cancer: Data from 3335 cases of lung adenocarcinoma.

OBJECTIVES: The Lepidic Component (LP) identifies a subgroup with an excellent prognosis for lung adenocarcinoma (LUAD). Our research aimed to propose an improved pathological T (pT) stage for LUAD based on LP. MATERIALS AND METHODS: Totally, 3335 surgical patients with pathological stage I LUAD were incorporated. Factors affecting survival were investigated by analyzing recurrence-free survival (RFS) and overall survival (OS) using the Kaplan-Meier method and Cox regression analyses. Subgroup analysis based on Lepidic Ratio (LR) was further evaluated. The net benefit from the modified pT category (pTm) was assessed using the Area Under the time-dependent Receiver Operating Curve (AUC), Harrell's Concordance Index (C-index), Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). RESULTS: The presence of LP (LP+) was identified in 1425 (42.7 %) patients, indicating a significantly better RFS (P < 0.001) and OS (P < 0.001) than those without LP, and similar results were reproduced in pT1a-pT2a subcategory (P < 0.050 for all). Multivariable Cox analysis revealed LP+ as an independent prognostic factor for both RFS (HR, 0.622; P < 0.001) and OS (HR, 0.710; P = 0.019). However, lepidic ratio (LR) was not independently associated with both RFS and OS for LP+ patients. The 5-year RFS and OS rates between T1a (LP-) and T1b (LP+), T1b (LP-) and T1c (LP+), and T1b (LP-) and T2a (LP+) were comparable (P > 0.050 for all). After modification, compared with current 8th edition pT stage system (pT8), pTm independently predicted RFS and OS, and AUCs, c-index, NRI, and IDI analysis all demonstrated pTm holds better discrimination performances than pT8 for LUAD prognosis. CONCLUSION: LP can be an additional down-staged T descriptor for pathological stage I LUAD and improve the survival predictive performance of reclassification.

Donor-recipient intermicrobial interactions impact transfer of subspecies and fecal microbiota transplantation outcome.

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.