p300/CBP degradation is required to disable the active AR enhanceosome in prostate cancer.

Prostate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which is exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia. Degradation of p300/CBP rapidly depleted acetylation marks associated with the active AR enhanceosome, which was only partially phenocopied by inhibition of their reader bromodomains. Notably, H2BNTac was effectively abrogated only upon p300/CBP degradation, which led to a stronger suppression of p300/CBP-dependent oncogenic gene programs relative to bromodomain inhibition or the inhibition of its catalytic domain. In vivo experiments using an orally active p300/CBP proteolysis targeting chimera (PROTAC) degrader (CBPD-409) showed that p300/CBP degradation potently inhibited tumor growth in preclinical models of castration-resistant prostate cancer and synergized with AR antagonists. While mouse p300/CBP orthologs were effectively degraded in host tissues, prolonged treatment with the PROTAC degrader was well tolerated with no significant signs of toxicity. Taken together, our study highlights the pivotal role of p300/CBP in maintaining the active AR enhanceosome and demonstrates how target degradation may have functionally distinct effects relative to target inhibition, thus supporting the development of p300/CBP degraders for the treatment of advanced prostate cancer.

Discovery of CBPD-268 as an Exceptionally Potent and Orally Efficacious CBP/p300 PROTAC Degrader Capable of Achieving Tumor Regression.

CBP/p300 proteins are key epigenetic regulators and promising targets for the treatment of castration-resistant prostate cancer and other types of human cancers. Herein, we report the discovery and characterization of CBPD-268 as an exceptionally potent, effective, and orally efficacious PROTAC degrader of CBP/p300 proteins. CBPD-268 induces CBP/p300 degradation in three androgen receptor-positive prostate cancer cell lines, with DC50 ≤ 0.03 nM and Dmax > 95%, leading to potent cell growth inhibition. It has an excellent oral bioavailability in mice and rats. Oral administration of CBPD-268 at 0.3-3 mg/kg resulted in profound and persistent CBP/p300 depletion in tumor tissues and achieved strong antitumor activity in the VCaP and 22Rv1 xenograft tumor models in mice, including tumor regression in the VCaP tumor model. CBPD-268 was well tolerated in mice and rats and displayed a therapeutic index of >10. Taking these results together, CBPD-268 is a highly promising CBP/p300 degrader as a potential new cancer therapy.

Discovery of CBPD-409 as a Highly Potent, Selective, and Orally Efficacious CBP/p300 PROTAC Degrader for the Treatment of Advanced Prostate Cancer.

CBP/p300 are critical transcriptional coactivators of the androgen receptor (AR) and are promising cancer therapeutic targets. Herein, we report the discovery of highly potent, selective, and orally bioavailable CBP/p300 degraders using the PROTAC technology with CBPD-409 being the most promising compound. CBPD-409 induces robust CBP/p300 degradation with DC50 0.2-0.4 nM and displays strong antiproliferative effects with IC50 1.2-2.0 nM in the VCaP, LNCaP, and 22Rv1 AR+ prostate cancer cell lines. It has a favorable pharmacokinetic profile and achieves 50% of oral bioavailability in mice. A single oral administration of CBPD-409 at 1 mg/kg achieves >95% depletion of CBP/p300 proteins in the VCaP tumor tissue. CBPD-409 exhibits strong tumor growth inhibition and is much more potent and efficacious than two CBP/p300 inhibitors CCS1477 and GNE-049 and the AR antagonist Enzalutamide. CBPD-409 is a promising CBP/p300 degrader for further extensive evaluations for the treatment of advanced prostate cancer and other types of human cancers.

Clinical features and management of germline CEBPA-mutated carriers.

Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPAp30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPAothers). Germline CEBPAp30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPAothers carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPAp30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPAothers carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations.

Discovery of ERD-3111 as a Potent and Orally Efficacious Estrogen Receptor PROTAC Degrader with Strong Antitumor Activity.

Estrogen receptor α (ERα) is a prime target for the treatment of ER-positive (ER+) breast cancer. Despite the development of several effective therapies targeting ERα signaling, clinical resistance remains a major challenge. In this study, we report the discovery of a new class of potent and orally bioavailable ERα degraders using the PROTAC technology, with ERD-3111 being the most promising compound. ERD-3111 exhibits potent in vitro degradation activity against ERα and demonstrates high oral bioavailability in mice, rats, and dogs. Oral administration of ERD-3111 effectively reduces the levels of wild-type and mutated ERα proteins in tumor tissues. ERD-3111 achieves tumor regression or complete tumor growth inhibition in the parental MCF-7 xenograft model with wild-type ER and two clinically relevant ESR1 mutated models in mice. ERD-3111 is a promising ERα degrader for further extensive evaluations for the treatment of ER+ breast cancer.

Recombinant GM-CSF enhances the bactericidal ability of PMNs by increasing intracellular IL-1ß and improves the prognosis of secondary Pseudomonas aeruginosa pneumonia in sepsis.

This study tested the hypothesis that recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances polymorphonuclear neutrophils (PMNs) via interleukin (IL)-1ß to improve the prognosis of secondary infection in sepsis. The latter stage of sepsis is prone to induce immunosuppression, resulting in secondary fatal infections. Recombinant GM-CSF has become a way for sepsis-induced immunosuppression due to its immunomodulatory effect. However, the functional impact of GM-CSF on PMNs in sepsis remains obscure. This study aimed to study the role of recombinant GM-CSF on the bactericidal ability of PMNs in septic mice, assessing its effect on the prognosis of secondary pneumonia, and explore the mechanism of recombinant GM-CSF by intervening PMNs in patients with sepsis. The C57BL/6J sepsis mouse model was induced by cecal ligation and puncture. Recombinant murine GM-CSF (rmGM-CSF) was used in vivo when mice developed immunosuppression, which was characterized by abnormal bactericidal function of PMNs in peripheral blood. rmGM-CSF improved the prognosis of secondary pneumonia and reversed the function of PMNs. PMNs isolated by Percoll from septic patients were treated by recombinant human GM-CSF (rhGM-CSF) in vitro. The expression of CD11b, reactive oxygen species, phagocytosis, and neutrophil extracellular trap release in PMNs were enhanced by rhGM-CSF treatments. Whole-transcriptomic sequencing of mouse PMNs indicated that recombinant GM-CSF increased the expression of Il1b gene in PMNs. Blocking and inhibiting IL-1ß release effectively counteracted the enhancing effect of GM-CSF on the bactericidal function of PMNs. rmGM-CSF enhances the bactericidal function of PMNs in vivo and improves the prognosis of secondary pneumonia in septic mice, and recombinant GM-CSF increases IL-1ß precursor reserves, which, if stimulated, can rapidly enhance the bactericidal capacity of PMNs.

Efficacy of Antibiotic Cement in Preserving Endoplants After Infection With Plate Exposure.

Background: To study the feasibility and efficacy of antibiotic cement in preserving endoplants after infection in patients with early tibial plateau fracture on plate exposure. Patients and Methods: A retrospective analysis of 23 patients treated for post-operative infection with plate exposure after tibial plateau fracture between 2017 and 2021. They were divided into the observation group (10 patients) and the control group (13 patients). Total operation time, length of hospitalization, hospitalization cost, the number of surgeries, white blood cell (WBC) count, neutrophil (NEUT) count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), the post-operative evaluation index, and complications were observed during the follow-up period. Results: All patients were followed up for 6 to 12 months; wound healing was observed in both groups. The total operation time for patients in the control group was longer compared with the observation group. However, the length of hospitalization, hospitalization cost, and number of surgeries in the observation group were less compared with the control group. No difference in WBC, NEUT, ESR, and CRP levels was observed one day after surgery. Furthermore, WBC, NEUT, ESR, and CRP levels were higher in patients in the control group compared with the observation group 72 hours after surgery. There were no differences in the post-operative evaluation index and complications in both groups. Conclusions: The antibiotic cement coating used for treating early post-operative infection in patients with tibial plateau fracture could effectively control infection while retaining endoplant, thereby promoting wound healing. It could also reduce pain and the medical burden on patients.

Transcriptional Regulatory Network of Plant Cadmium Stress Response.

Cadmium (Cd) is a non-essential heavy metal with high toxicity to plants. Plants have acquired specialized mechanisms to sense, transport, and detoxify Cd. Recent studies have identified many transporters involved in Cd uptake, transport, and detoxification. However, the complex transcriptional regulatory networks involved in Cd response remain to be elucidated. Here, we provide an overview of current knowledge regarding transcriptional regulatory networks and post-translational regulation of the transcription factors involved in Cd response. An increasing number of reports indicate that epigenetic regulation and long non-coding and small RNAs are important in Cd-induced transcriptional responses. Several kinases play important roles in Cd signaling that activate transcriptional cascades. We also discuss the perspectives to reduce grain Cd content and improve crop tolerance to Cd stress, which provides a theoretical reference for food safety and the future research of plant varieties with low Cd accumulation.

Autophagy and multivesicular body pathways cooperate to protect sulfur assimilation and chloroplast functions.

Autophagy and multivesicular bodies (MVBs) represent 2 closely related lysosomal/vacuolar degradation pathways. In Arabidopsis (Arabidopsis thaliana), autophagy is stress-induced, with deficiency in autophagy causing strong defects in stress responses but limited effects on growth. LYST-INTERACTING PROTEIN 5 (LIP5) is a key regulator of stress-induced MVB biogenesis, and mutation of LIP5 also strongly compromises stress responses with little effect on growth in Arabidopsis. To determine the functional interactions of these 2 pathways in Arabidopsis, we generated mutations in both the LIP5 and AUTOPHAGY-RELATED PROTEIN (ATG) genes. atg5/lip5 and atg7/lip5 double mutants displayed strong synergistic phenotypes in fitness characterized by stunted growth, early senescence, reduced survival, and greatly diminished seed production under normal growth conditions. Transcriptome and metabolite analysis revealed that chloroplast sulfate assimilation was specifically downregulated at early seedling stages in the atg7/lip5 double mutant prior to the onset of visible phenotypes. Overexpression of adenosine 5'-phosphosulfate reductase 1, a key enzyme in sulfate assimilation, substantially improved the growth and fitness of the atg7/lip5 double mutant. Comparative multi-omic analysis further revealed that the atg7/lip5 double mutant was strongly compromised in other chloroplast functions including photosynthesis and primary carbon metabolism. Premature senescence and reduced survival of atg/lip5 double mutants were associated with increased accumulation of reactive oxygen species and overactivation of stress-associated programs. Blocking PHYTOALEXIN DEFICIENT 4 and salicylic acid signaling prevented early senescence and death of the atg7/lip5 double mutant. Thus, stress-responsive autophagy and MVB pathways play an important cooperative role in protecting essential chloroplast functions including sulfur assimilation under normal growth conditions to suppress salicylic-acid-dependent premature cell-death and promote plant growth and fitness.

Shared and Related Molecular Targets and Actions of Salicylic Acid in Plants and Humans.

Salicylic acid (SA) is a phenolic compound produced by all plants that has an important role in diverse processes of plant growth and stress responses. SA is also the principal metabolite of aspirin and is responsible for many of the anti-inflammatory, cardioprotective and antitumor activities of aspirin. As a result, the number of identified SA targets in both plants and humans is large and continues to increase. These SA targets include catalases/peroxidases, metabolic enzymes, protein kinases and phosphatases, nucleosomal and ribosomal proteins and regulatory and signaling proteins, which mediate the diverse actions of SA in plants and humans. While some of these SA targets and actions are unique to plants or humans, many others are conserved or share striking similarities in the two types of organisms, which underlie a host of common biological processes that are regulated or impacted by SA. In this review, we compare shared and related SA targets and activities to highlight the common nature of actions by SA as a hormone in plants versus a therapeutic agent in humans. The cross examination of SA targets and activities can help identify new actions of SA and better explain their underlying mechanisms in plants and humans.

Effect of Minimally Invasive Internal Arch Nailing Surgery on Tissue Traumatic Stress Response in Patients with Vertebral Fractures.

Objective: To analyze the influence of minimally invasive arch root nailing internal fixation surgery on tissue traumatic stress response in patients with vertebral fractures and explore the advantages of this treatment. Methods: One hundred and thirty-six patients with vertebral fractures admitted to our hospital from January 2020 to January 2022 were selected and divided into two groups based on the treatment method: the control group was treated with open arch root nail internal fixation surgery and the study group was treated with minimally invasive arch root nail internal fixation. The lumbar spine function, ODI, VAS, JOA score, complications, inflammation, and stress response were compared between the two groups. Results: After the operation, the ratio of intervertebral space and anterior edge height increased, and the Cobb angle decreased in both groups; the surgical incision, hospital stay, and operation time in the study group were shorter than those in the control group, and the intraoperative drainage volume and intraoperative blood loss were smaller than those in the control group (P < 0.05); before surgery, there was no significant difference in ODI and VAS scores between the two groups (P > 0.05). After surgery, the ODI and VAS scores in the two groups were significantly decreased, and the JOA score was significantly increased; complications occurred in the control group and the study. The incidence of complications in the study group was lower than that in the control group (P < 0.05); after surgery, compared with the control group, the serum TNF-α, CRP levels, and stress response indexes of the study group decreased more significantly (P < 0.05). Conclusion: Minimally invasive pedicle screw fixation has high safety and obvious advantages. The patient's stress response index and pain level are low, and it will not cause obvious damage to the patient. The postoperative lumbar spine function is significantly improved, which is beneficial to the patient's postoperative recovery. It is easy to operate, will not damage the thoracic and lumbar vertebrae significantly, and the fluoroscopy time is relatively short, and it has a good recovery effect. Therefore, minimally invasive internal arch nailing surgery can be used as the preferred treatment for patients with vertebral fractures.

Serum Creatinine/Cystatin C Ratio as a Predictor of In-hospital Mortality in Patients Hospitalized with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Low serum creatinine/cystatin C ratio (CCR) is associated with unfavorable characteristics in patients with chronic obstructive pulmonary disease (COPD); however, the relationship between CCR and in-hospital mortality of patients with acute exacerbation of COPD (AECOPD) is unexplored. Our objective was to assess the value of CCR for predicting in-hospital mortality of patients hospitalized with AECOPD. METHODS: Patients with AECOPD (n = 597) were retrospectively enrolled. Patient's clinical characteristics and laboratory tests, including serum cystatin C and creatinine, were reviewed. The prediction value of CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. Factors potentially impacting in-hospital mortality were investigated using univariate and multivariate logistic regression analyses. RESULTS: Mortality rate during hospitalization was 10.05%. CCR was lower in non-surviving vs. survived patients (41.67 vs. 61.52, P < 0.001). AUC value for CCR for in-hospital mortality prediction was 0.79 [95% confidence interval (CI) 0.73-0.85]. On multivariate logistic regression analysis, in-hospital mortality was strongly associated with CCR < 52.27 [odds ratio (OR) 6.23, 95% CI (3.00-12.92), P < 0.001], age ≥ 81 years [OR 2.97, 95% CI (1.20-7.37), P = 0.019], oxygenation index < 300 [OR 3.28, 95% CI (1.27-8.44), P = 0.014], CRP > 8 mg/L [OR 1.84, 95% CI (1.15-2.95), P = 0.012], and D-dimer > 500 ng/L [OR 5.19, 95% CI (1.51-17.79), P = 0.009]. CONCLUSIONS: CCR was significantly lower, and is a potential prognostic indicator, in patients with AECOPD who died during hospitalization.

Specialized endoplasmic reticulum-derived vesicles in plants: Functional diversity, evolution, and biotechnological exploitation.

A central role of the endoplasmic reticulum (ER) is the synthesis, folding and quality control of secretory proteins. Secretory proteins usually exit the ER to enter the Golgi apparatus in coat protein complex II (COPII)-coated vesicles before transport to different subcellular destinations. However, in plants there are specialized ER-derived vesicles (ERDVs) that carry specific proteins but, unlike COPII vesicles, can exist as independent organelles or travel to the vacuole in a Golgi-independent manner. These specialized ERDVs include protein bodies and precursor-accumulating vesicles that accumulate storage proteins in the endosperm during seed development. Specialized ERDVs also include precursor protease vesicles that accumulate amino acid sequence KDEL-tailed cysteine proteases and ER bodies in Brassicales plants that accumulate myrosinases that hydrolyzes glucosinolates. These functionally specialized ERDVs act not only as storage organelles but also as platforms for signal-triggered processing, activation and deployment of specific proteins with important roles in plant growth, development and adaptive responses. Some specialized ERDVs have also been exploited to increase production of recombinant proteins and metabolites. Here we discuss our current understanding of the functional diversity, evolutionary mechanisms and biotechnological application of specialized ERDVs, which are associated with some of the highly remarkable characteristics important to plants.

Circular RNA Hsa_circ_0006766 targets microRNA miR-4739 to regulate osteogenic differentiation of human bone marrow mesenchymal stem cells.

Circular RNAs (circRNAs) are emerging as important regulators in bone metabolism, which is mediated by microRNA (miRNA) sponges. However, it is not clear how circRNA regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs).Therefore, based on the previous circRNA chip results, hsa_circ_0006766, which is differentially expressed in the osteogenic differentiation of hBM-MSCs, was screened out, and bioinformatics analysis was performed to predict potential target miRNAs. During osteogenic differentiation of hBM-MSCs, hsa_circ_0006766 and its target miRNAs (miR-4739, miR-619-5p, miR-5787, miR-7851-3p, and miR-3192-5p) were detected by quantitative Real Time-PCR (qRT-PCR). Target gene prediction for the differentially expressed target miRNAs was performed, and target genes were validated by dual-luciferase reporter gene assay and qRT-PCR. It is shown that hsa_circ_0006766 was up-regulated and miR-4739 was down-regulated during osteogenic differentiation of hBM-MSCs.Moreover, the target gene Notch2 was predicted to be highly expressed during osteogenic differentiation. And dual-luciferase assay proved that Notch2 was the gene targeting to miR-4739. Taken together, our finding confirmed that hsa_circ_0006766 may act as a major regulatory part in osteogenic differentiation of hBM-MSCs via an hsa_circ_0006766-miR-4739-Notch2 regulatory axis. Accordingly, hsa_circ_0006766 may affect the development of osteoporosis and may thus become a therapeutic target.

Inhibition of TNFR1 Attenuates LPS Induced Apoptosis and Inflammation in Human Nucleus Pulposus Cells by Regulating the NF-KB and MAPK Signalling Pathway.

Intervertebral disc degeneration (IDD) is accompanied by nucleus pulposus (NP) cell apoptosis, inflammation, and extracellular matrix degradation. Tumour necrosis factor receptor 1 (TNFR1) is a receptor of TNF-α, and is deeply involved in the processes of IDD. However, the effect of TNFR1 inhibition on IDD is not clear. Herein, we report that TNFR1 was increased in LPS-treated HNPCs. The aim of this study was to investigate the potential therapeutic effect of TNFR1 siRNA and selective antagonists of TNFR1 (GSK1995057) on HNPC damage. The results showed that the blockade of TNFR1 by TNFR1 siRNA and GSK1995057 effectively suppressed the cell viability loss, apoptosis, and inflammation induced by LPS in HNPCs. Furthermore, we found that TNFR1 siRNA and GSK1995057 inhibited activation of the NF-KB and MAPK signalling pathways in LPS-stimulated HNPCs. In summary, the blockade of TNFR1 effectively suppressed LPS-induced apoptosis and inflammation in HNPCs through the NF-KB and MAPK signalling pathways. This revealed that the blockade of TNFR1 may provide a potential therapeutic treatment for IDD.

Salicylic acid application alleviates cadmium accumulation in brown rice by modulating its shoot to grain translocation in rice.

Cadmium (Cd) contamination, which poses a serious threat to human health, has been recognized as a major threat to the agricultural system and crop production. Salicylic acid (SA) is a signaling molecule that plays an important role in against Cd toxicity. Previously, we found that spraying rice with SA could reduce the Cd accumulation in rice grains grown in Cd-contaminated soil. In this study, we studied the specific mechanism of SA spray on reducing Cd accumulation in rice grain. The results showed that treatment with SA could alleviate Cd toxicity in rice by increasing the activities of antioxidant enzymes that reduce hydrogen peroxide (H2O2) accumulation, but not by changing the pH, or total or available Cd of the soil. The key factor by which SA treatment reduced Cd accumulation in rice grains was by decreasing the Cd content in rice leaves at the flowering stage. This indicated that SA could modulate the Cd accumulation in shoots, reducing the Cd translocation to rice grains. Furthermore, SA could increase the H2O2 content, activating the SA-signaling pathway and modulating the expression levels of Cd transporters (OsLCT1 and OsLCD) in rice leaves to increase Cd tolerance and reduce Cd accumulation in the rice grain. Thus, spraying rice with SA may be effective measure to cope with Cd contamination in paddy soils.

Identifying 8-mRNAsi Based Signature for Predicting Survival in Patients With Head and Neck Squamous Cell Carcinoma via Machine Learning.

Cancer stem cells (CSCs) have been characterized by several exclusive features that include differentiation, self-renew, and homeostatic control, which allows tumor maintenance and spread. Recurrence and therapeutic resistance of head and neck squamous cell carcinomas (HNSCC) have been identified to be attributed to CSCs. However, the biomarkers led to the development of HNSCC stem cells remain less defined. In this study, we quantified cancer stemness by mRNA expression-based stemness index (mRNAsi), and found that mRNAsi indices were higher in HNSCC tissues than that in normal tissue. A significantly higher mRNAsi was observed in HPV positive patients than HPV negative patients, as well as in male patients than in female patients. The 8-mRNAsi signature was identified from the genes in two modules which were mostly related to mRNAsi screened by weighted gene co-expression network analysis. In this prognostic signatures, high expression of RGS16, LYVE1, hnRNPC, ANP32A, and AIMP1 focus in promoting cell proliferation and tumor progression. While ZNF66, PIK3R3, and MAP2K7 are associated with a low risk of death. The riskscore of eight signatures have a powerful capacity for 1-, 3-, 5-year of overall survival prediction (5-year AUC 0.77, 95% CI 0.69-0.85). These findings based on stemness indices may provide a novel understanding of target therapy for suppressing HNSCC stem cells.

Exosomal CA125 as A Promising Biomarker for Ovarian Cancer Diagnosis.

The main diagnostic indicators of ovarian cancer (OC), including carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4), show good sensitivity and poor specificity or vice versa. This study investigated changes in CA125 and HE4 expression and their correlation in serum-derived exosomes of 55 patients with OC (OC group), 33 patients with malignant tumors (non-OC group), and 55 normal controls (NC group). We compared serum and exosomal CA125 and HE4 levels to determine whether their contents in exosomes were elevated. We also compared the diagnostic efficacy of serum HE4, serum CA125, exosomal CA125, and serum HE4+exosomal CA125 in OC using the receiver operating characteristic (ROC) curve. CA125 levels in serum-derived exosomes in all groups significantly increased (P < 0.0001) compared with serum CA125 levels. HE4 was undetected in exosomes. The ROC curve showed the following values: serum CA125: 0.9093 (area), 87.27% (sensitivity), and 90.91% (specificity); serum HE4: 0.9302, 83.64%, and 94.55%; exosomal CA125: 0.9755, 94.55%, and 92.73%; and serum HE4+exosomal CA125: 0.9861, 96.36%, and 92.73%. In conclusion, CA125 can be detected at higher levels in exosomes than in serum, significantly improving OC diagnosis sensitivity. The serum HE4+exosomal CA125 combination significantly improves OC diagnostic efficiency.

Potential diagnostic value of PD-1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced skeletal disorder. Bone mineral density (BMD) testing is the gold standard for diagnosing osteoporosis. However, its sensitivity for fracture risk assessment is low. Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule implicated in the pathophysiology of bone remodeling, but its role in osteoporosis has not yet been explored. Thus, this study aimed to assess the expression and diagnostic utility of PD-1 in PMOP. METHODS: A total of 56 patients with PMOP and 37 postmenopausal healthy controls (NC) were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation, and PD-1 expression was measured by quantitative polymerase chain reaction (qPCR). Pearson's correlation test was performed to explore the associations between PD-1 level and clinical variables, while receiver operating characteristic (ROC) curve analysis was used to evaluate the potential diagnostic value of PD-1 in patients with PMOP. RESULTS: We found that PD-1 level was significantly upregulated in the PBMCs of PMOP patients than those of NC (P = .016). PD-1 expression was positively correlated with C-reactive protein (CRP) levels. ROC curve analysis showed that PD-1 had certain diagnostic value for PMOP (area under the curve = 0.65, standard error = 0.06, 95% confidence interval [0.53,0.76], P = .016), with a sensitivity and specificity of 44.64% and 81.08%, respectively. CONCLUSION: Programmed cell death protein 1 is significantly upregulated in the PBMCs of PMOP patients and has certain diagnostic value for PMOP.

Soil cadmium extraction in Chinese cabbage and cabbage intercropping / Extração de cádmio no solo em repolho chinês e consorciação de repolho

ABSTRACT: Toxic metals contamination of soil has become a serious problem in recent years. In this study, Chinese cabbage (a relatively high-accumulator of cadmium (Cd)) and cabbage (a relatively low-accumulator of Cd) were cultured in monoculture and in intercropping in the Cd-contaminated soil, to evaluate the effect of intercropping on the alteration of Cd extraction. Both the pot experiments and field experiments indicated that intercropping increased the Cd extraction by Chinese cabbage and decreased the Cd extraction by cabbage. Thus, Cd extraction was advanced while safe production was obtained. Further pot experiment was conducted to investigate the alterations of soil Cd fractions, soil pH, and soil enzyme activities to reveal their possible relationship with Cd extraction between different planting patterns. Results revealed that three individual Chinese cabbages in one intercropping pot played the same effect on alteration of these factors as six individual Chinese cabbages in one monoculture pot. The intercropping increased Cd extraction by Chinese cabbage and decreased Cd extraction by cabbage, probably by influencing mechanisms such as soil enzyme activities (especially the urease activity) in the cultivation system. Effect of intercropping on Cd accumulation is an important issue in cultivation of vegetables in potentially contaminated land.

RESUMO: A contaminação do solo por metais tóxicos tornou-se um problema grave nos últimos anos. Neste estudo, dois tipos de repolhos, o repolho chinês (maior acumulador de cádmio (Cd)) e o repolho comum (menor acumulador de Cd) foram cultivados em monocultivo e em consórcio, em solo contaminado com esse metal, para avaliar o efeito do consórcio na extração de Cd do solo. Os experimentos em vasos de campo indicaram que o consórcio aumentou a extração desse metal pelo repolho chinês e diminuiu a extração pelo repolho comum. Assim, aumentou a extração de Cd do solo, proporcionando segurança alimentar. Outro experimento em vaso foi conduzido para investigar as alterações das frações de Cd do solo, o pH do solo e atividades enzimáticas do solo, para revelar possíveis efeitos na extração desse metal entre os sistemas de plantio. Os resultados do experimento em vaso revelaram que três repolhos da china, em cultivo consorciado, proporcionaram o mesmo efeito nessas variáveis, que os observados com seis plantas desse tipo de repolho, em monocultura. O consórcio influenciou as frações de Cd do solo devido a maior influência das hortaliças no pH do solo e nas atividades enzimáticas (especialmente a urease), resultando maior extração de Cd pelo repolho chinês e menor pelo repolho comum.