DUSP22-rearranged primary cutaneous CD30-positive T-cell lymphoproliferative disorders and adult T-cell leukemia/lymphoma frequently share the LEF1+/TIA1- immunophenotype.

DUSP22 rearrangements are genetic alterations observed in a subset of systemic anaplastic large cell lymphoma (S-ALCL), primary cutaneous anaplastic large cell lymphoma (C-ALCL), and lymphomatoid papulosis (LyP). Previous investigations have shown that the LEF1+/TIA1- immunoprofile and MSC E116K mutations are highly associated with DUSP22 rearrangement in ALCL. However, the existing literature primarily focuses on S-ALCL. Our understanding of the LEF1/TIA1 immunoprofile and MSC mutation status in C-ALCL/LyP is still limited. In this study, we aimed to assess LEF1/TIA1 expression and MSC mutations in a cohort of 23 C-ALCL/LyP cases, along with a control group of histological mimickers. DUSP22 rearrangements were detected by fluorescence in situ hybridization in eight cases (6/10 C-ALCL, 2/13 LyP). We found LEF1 expression in five out of eight (63%) DUSP22-rearranged cases (3/6 C-ALCL, 2/2 LyP), and none of the 15 cases lacking DUSP22 rearrangements. Furthermore, we also found frequent LEF1 expression in adult T-cell leukemia/lymphoma (ATLL; 10 of 11, 91%) within the control group. TIA1 expression was consistently negative in all DUSP22-rearranged C-ALCL/LyP and ATLL cases tested. MCS E116K mutation was identified in one of five DUSP22-rearranged C-ALCL cases. RNA sequencing of a DUSP22-rearranged C-ALCL revealed a novel DUSP22::SNHG fusion coexisting with a CD58::WNT2B fusion. In conclusion, our findings demonstrated a lower rate of LEF1 expression in DUSP22-rearranged C-ALCL/LyP compared to previous reports that predominantly focused on S-ALCL. Moreover, we observed that the majority of ATLL cases also expressed LEF1, suggesting that the LEF1+/TIA1- immunoprofile does not differentiate DUSP22-rearranged C-ALCL/LyP from ATLL.

Antimicrobial peptide LL37 and regulatory T cell associated with late-onset sepsis in very preterm infants.

Stem cell therapy may prevent late-onset sepsis (LOS) via antimicrobial peptide LL37 secretion and regulatory T cell (Treg) regulation. The early prediction of LOS is still a challenge. This study evaluated whether immunological state of LL37 or Tregs precedes LOS. We firstly analyzed the LL37 level, Treg proportion, and LOS incidence in very preterm infants treated with autologous cord blood mononuclear cells (ACBMNCs) in our previous trial. Then, we constructed a prediction model and built validation cohort. We found ACBMNC intervention reduced the incidence of LOS from 27.3% to 6.9% (p = 0.021). LL37 and Treg abundances were higher in the ACBMNCs group. The nomogram demonstrated that early-life Treg and LL37 characteristics were closely associated with LOS (area under the curve, AUC 0.936), with implications for early prediction and timely clinical management. This composite model was also helpful to evaluate the beneficial effect of ACBMNCs intervention on LOS, thus promoting translational research.

Umbilical cord blood cell characteristics in very preterm neonates for autologous cell therapy of preterm-associated complications.

BACKGROUND: There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. METHODS: Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. RESULTS: Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. CONCLUSION: UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

Study on the anti-cancer activity of α-phenethylamine ferrocenecarboxylic acid co-crystals.

Ferrocene derivatives show a wide range of pharmacological activities in the medical field, especially in the anti-tumor field, and can be used as candidate drugs or lead compounds for the treatment of tumors and other diseases. And α-phenethylamine is an important intermediate for the preparation of fine chemical products. (R)-(+)-1-Phenethylamine ferrocenecarboxylic acid/(S)-(-)-1-phenethylamine ferrocenecarboxylic acid were prepared, named compounds 1 and 2, respectively. Single crystal X-ray diffraction showed that compounds 1 and 2 crystallized in the orthorhombic system space group P21 21 21 , and the crystal structures of compounds 1 and 2 exhibited mirror symmetry. The inhibitory effect of two compounds on SW480, MDA-MB-231, and H1299 cells was tested by MTT colorimetry. The IC50 values of the compounds against cancer cells were also calculated. The anti-cancer effect was more pronounced for compounds in the S-configuration. Compound 2 made the wild-type cancer cells undergo apoptosis, thus preventing cancer; it also had the function of helping the cell gene repair defects.

A study on the effectiveness of sodium selenite in treating cadmium and perfluoro octane sulfonic (PFOS) poisoned zebrafish (Danio rerio).

Perfluoro octane sulfonate (PFOS) and cadmium (Cd) are toxic elements in the environment. As a micronutrient trace element, selenium (Se) can mitigate the adverse effects induced by PFOS and Cd. However, few studies have examined the correlation between Se, PFOS and Cd in fish. The present study focused on the antagonistic effects of Se on PFOS+Cd-induced accumulation in the liver of zebrafish. The fish was exposed to PFOS (0.08mg/L), Cd (1mg/L), PFOS+ Cd (0.08 mg/L PFOS+1 mg/L Cd), L-Se (0.07mg/L Sodium selenite +0.08mg/L PFOS+1mg/L Cd), M-Se (0.35mg/L Sodium selenite + 0.08mg/L PFOS+ 1 mg/L Cd), H-Se (1.75 mg/L Sodium selenite + 0.08 mg/L PFOS+ 1mg/L Cd) for 14d. The addition of selenium to fish exposed to PFOS and Cd has been found to have significant positive effects. Specifically, selenium treatments can alleviate the adverse effects of PFOS and Cd on fish growth, with a 23.10% improvement observed with the addition of T6 compared to T4. In addition, selenium can alleviate the negative effects of PFOS and Cd on antioxidant enzymes in zebrafish liver, thus reducing the liver toxicity caused by PFOS and Cd. Overall, the supplementation of selenium can reduce the health risks to fish and mitigate the injuries caused by PFOS and Cd in zebrafish.

Osimertinib Covalently Binds to CD34 and Eliminates Myeloid Leukemia Stem/Progenitor Cells.

Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia. SIGNIFICANCE: Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.

Comprehensive evaluation of benign and malignant etiologies of different serous effusions with the International System for Reporting Serous Fluid Cytopathology: A multi-institutional study in Taiwan.

BACKGROUND: The International System for Reporting Serous Fluid Cytopathology (ISRSFC) was introduced globally in 2019 in response to the absence of a standardized reporting system for serous fluid cytology. This study presents experiences implementing this system across three distinct hospitals in Taiwan. METHODS: A total of 6177 serous fluid specimens in three hospitals in Taiwan between 2018 and 2020 were retrospectively reviewed and reclassified according to the ISRSFC. Cytohistological correlation and chart review were further performed to investigate etiologies and risks of malignancy (ROMs). RESULTS: Reclassification showed that 34 (0.7%) of 4838 pleural effusions were nondiagnostic (ND), 4086 (84.5%) were negative for malignancy (NFM), 201 (4.2%) were atypia of undetermined significance (AUS), 92 (1.9%) were suspicious for malignancy (SFM), and 425 (8.8%) were malignant (MAL). The 1231 ascites cases contained 13 (1.1%) ND, 1004 (81.6%) NFM, 53 (4.3%) AUS, 31 (2.5%) SFM, and 130 (10.6%) MAL specimens. In pleural effusions, the ROM was 2.9% for ND, 14.0% for NFM, 52.2% for AUS, 85.9% for SFM, and 95.1% for MAL. In ascites, it was 15.4% for ND, 19.1% for NFM, 52.8% for AUS, 83.9% for SFM, and 92.3% for MAL. In pericardial effusions, it was 0.0% for ND, 11.6% for NFM, 30.8% for AUS, 100.0% for SFM, and 95.2% for MAL. Different effusions' most common benign and malignant etiologies were also disclosed. CONCLUSIONS: These multi-institutional data have determined the diagnostic usefulness of the ISRSFC, which provides pathologists and physicians with invaluable assistance in correctly classifying effusions for further management.

Three-dimensional instrument polarization analysis and optimization of liquid-crystal-based Stokes polarimeter.

The Stokes polarimeter based on liquid crystal variable retarders (LCVRs) is a space polarization measurement technology widely used. However, due to the tilt of the optic axis of the LCVR with the driving voltage in the direction of light propagation and the interference in LCVR, the LCVRs-based Stokes polarimeter produces a large instrument polarization, which affects the accurate polarization measurement. In this paper, we combine polarization ray tracing with multi-beam interference, and establish a general three-dimensional polarization analysis model of the LCVRs-based Stokes polarimeter. The simulation results of adjusting the LCVR voltage to reduce the instrument polarization are analyzed, and the variation of polarization measurement accuracy with the field of view before and after optimization of the LCVRs-based Stokes polarimeter is simulated and analyzed. A LCVR structure with additional films for matching the refractive index is proposed. According to the simulation results, this structure can significantly reduce the interference effects and reduce the impact of variations in liquid crystal layer thickness on the interference effects.

The relationship between parenting styles and adolescent problematic Internet use: A three-level meta-analysis.

Background and aims: Problematic Internet use (PIU) has become a global public health problem. It has been suggested that parenting style is associated with adolescent PIU. However, the evidence in favor of this view is mixed. Based on the PRISMA method, the present study employed three-level meta-analysis approach to investigate the relationship between these two variables and further explore potential moderators. Methods: After a systematic search for published articles, 35 studies were included, reporting 171 effect sizes (N = 40,587). Results: The results showed that positive parenting styles were significantly negatively related to PIU. This association was moderated by gender, age, publication year, and measurements of PIU, but was not by culture and measurements of parenting styles. Negative parenting styles were significantly positively related to PIU, which was moderated by publication year, culture, and sub-types of negative parenting, but not by gender, age, and measurements of both parenting styles and PIU. In addition, the correlation of PIU with negative parenting styles was stronger than that with positive parenting styles. Discussion and Conclusions: The present results demonstrated that parenting styles, especially punitive parenting styles, should be attached to more important when treating adolescent PIU.

Cytological Features of a Metastatic Angiosarcoma in the Lymph Node Diagnosed via Liquid-Based Cytology.

Angiosarcoma is a soft tissue sarcoma of vascular origin, with more than half of the cases arising in the skin and affecting primarily the face and scalp of elderly males. Furthermore, cutaneous angiosarcoma exhibits a higher incidence of lymph node metastases than other types of sarcomas. Angiosarcomas are rarely aspirated and are occasionally encountered on cytological samples. It is a diagnostic challenge in evaluating fine needle aspiration (FNA) from a metastatic angiosarcoma without the knowledge of prior history. We present a case of scalp angiosarcoma with disease progression to erythroderma and cervical lymphadenopathy 20 months after. FNA of the cervical node revealed vasoformative features, including hemophagocytosis, formation of an intracytoplasmic lumen/vacuole, endothelial wrapping, and cell grasping. The diagnosis of nodal metastasis by angiosarcoma was confirmed with immunohistochemistry (IHC) using two vascular markers on cell block sections. Our case demonstrates the recognizable cytomorphologic clues for this rare metastatic malignancy.

Yeast diversity in pit mud and related volatile compounds in fermented grains of chinese strong-flavour liquor.

Chinese strong-flavour liquor is produced via a traditional solid-state fermentation strategy facilitated by live microorganisms in pit mud-based cellars. For the present analysis, pit mud samples from different spatial locations within fermentation cellars were collected, and the yeast communities therein were assessed via culture-based and denaturing gradient gel electrophoresis (DGGE) approaches. These analyses revealed significant differences in the composition of yeast communities present in different layers of pit mud. In total, 29 different yeast species were detected, and principal component analyses revealed clear differences in microbial diversity in pit mud samples taken from different cellar locations. Culture-dependent strategies similarly detected 20 different yeast species in these samples. However, while Geotrichum silvicola, Torulaspora delbrueckii, Hanseniaspora uvarum, Saturnispora silvae, Issatchenkia orientalis, Candida mucifera, Kazachstania barnettii, Cyberlindnera jadinii, Hanseniaspora spp., Alternaria tenuissima, Cryptococcus laurentii, Metschnikowia spp., and Rhodotorula dairenensis were detected via a PCR-DGGE approach, they were not detectable in culture-dependent analyses. In contrast, culture-based approaches led to the identification of Schizosaccharomyces pombe and Debaryomyces hansenii in these pit mud samples, whereas they were not detected using DGGE fingerprints profiles. An additional HS-SPME-GC-MS-based analysis of the volatile compounds present in fermented grains samples led to the identification of 66 such compounds, with the highest levels of volatile acids, esters, and alcohols being detected in fermented grains from lower layer samples. A canonical correspondence analysis (CCA) suggested they were significant correlations between pit mud yeast communities and associated volatile compounds in fermented grains.

Prevention for moderate or severe BPD with intravenous infusion of autologous cord blood mononuclear cells in very preterm infants-a prospective non-randomized placebo-controlled trial and two-year follow up outcomes.

Background: Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. Methods: This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18-24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Findings: Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3-20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p = 0.018). There was no statistical significant difference in total BPD incidence (adjusted p = 0.106) or mortality (p = 1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p = 0.047). Specific immune cells including proportion of T cells (p = 0.04) and CD4+ T cells in lymphocytes (p = 0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p ï¼œ 0.001). Anti-inflammatory factor IL-10 was higher (p = 0.03), while pro-inflammatory factor such as TNF-a (p = 0.03) and C reactive protein (p ï¼œ 0.001) level was lower in intervention group than in control group after intervention. Interpretation: ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. Funding: This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

Enhancement of phytolith-occluded carbon accumulation of Moso bamboo response to temperatures elevation and different fertilization.

The accumulation of phytolith-occluded carbon (PhytOC) in Moso bamboo could be a novel long-term carbon sequestration strategy. The objective of this study was to investigate the effects of temperature change and different fertilization on PhytOC accumulation. The pot experiment was established with different fertilization (including control (CK), nitrogen fertilizers (N), silicon fertilizers (Si), and a combination of nitrogen and silicon (NSi)) under high- and low-temperature. Despite the different fertilization, the PhytOC accumulation of the high-temperature group increases by 45.3% on average compared with the low-temperature group, suggesting higher temperature is greatly beneficial to the PhytOC accumulation. Fertilization significantly increases the accumulation of PhytOC (increased by 80.7% and 48.4% on average for the low- and high-temperature group, respectively) compared with CK. However, the N treatment increased both Moso bamboo biomass and PhytOC accumulation. The difference in the accumulation of PhytOC in Si and NSi was insignificant, indicating the combination of N and Si didn't bring extra benefit to PhytOC accumulation compared to Si fertilizer alone. These results indicated the application of nitrogen fertilizer is a practical and effective method for enhancing long-term carbon sequestration for Moso bamboo. Based on our study, we conclude that global warming poses a positive effect on promoting the long-term carbon sequestration of Moso bamboo.

Wnt5a-Flt1 activation contributes to preterm altered cerebral angiogenesis after prenatal inflammation.

OBJECTIVE: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. METHODS: Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. RESULTS: The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. CONCLUSION: Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.

Hidden blood loss of minimally invasive hybrid lumbar interbody fusion: an analysis of influencing factors.

BACKGROUND: Lumbar interbody fusion(LIF) is the leading way to treat Lumbar Degenerative Diseases(LDD). At present, there is a lack of research on the influencing factors of hidden blood loss in minimally invasive hybrid lumbar interbody fusion. This study comprehensively explores the definite factors affecting the hidden blood loss in minimally invasive hybrid lumbar interbody fusion. MATERIALS AND METHODS: One hundred patients with Lumbar degenerative diseases who underwent minimally invasive hybrid lumbar interbody fusion in our center were included. Demographics, laboratory data, surgical data, and radiographic data were collected. The Gross equation and Sehat equation were used to calculate the estimated value of hidden blood loss. Multi-factor linear regression analysis was used to determine the influencing factors of hidden blood loss. RESULT: We reviewed and collected 100 patients who underwent minimally invasive hybrid approach, mean age 65 ± 10 years, male: female 37:63; 17 patients of diabetes and 83 patients of non-diabetes; Total blood loss was 645.59 ± 376.37 ml, hidden blood loss was 421.39 ± 337.45 ml, the hidden blood loss percentage was 57 ± 26%. Results from the multi-factorial linear regression model: Diabetes (p < 0.05), hypertension (p < 0.05), psoas thickness (p < 0.05) and dorsal extensor group thickness (p < 0.05) were potential risk factors for postoperative hidden blood loss. CONCLUSION: Although minimally invasive hybrid approach is minimally invasive surgery, there is still a significant amount of hidden blood loss. There is a greater risk of blood loss in diabetes, hypertension and preoperative MRI assessment of thickness of the psoas, thickness of the dorsal extensor group.

Autologous cord blood mononuclear cell infusion for the prevention of bronchopulmonary dysplasia in very preterm monozygotic twins: A study protocol for a randomized, placebo-controlled, double-blinded multicenter trial.

Background: Preterm-associated complications remain the main cause of neonatal death. Survivors face the challenges of short- and long-term complications. Among all complications, bronchopulmonary dysplasia (BPD) remains the first important cause of neonatal mortality and morbidity. Current treatment does not address this main preterm complication. Cord blood is regarded as a convenient source of stem cells. The paracrine bioactive factors of stem cells contribute to tissue repair and immune modulation. Our clinical studies and those of others have shown that cord blood cell infusion is both safe and possibly effective in the prevention and treatment of BPD. The therapeutic use of cord blood has emerged as a promising therapy. However, the genetic heterogeneity between control and intervention groups may reduce the comparability especially among small sample trials. The purpose of this study protocol is to investigate the effects of autologous cord blood mononuclear cell (ACBMNC) infusion on the prevention of BPD in very preterm monozygotic twins of less than 32 gestation weeks. Methods: In this prospective, randomized, placebo-controlled, double-blinded multicenter clinical trial, 60 pairs of monozygotic twin preterm neonates of less than 32 weeks admitted to the Neonatal Intensive Care Unit are randomly assigned to receive intravenous ACBMNC infusion (targeted at 5 × 107 cells/kg) or placebo (normal saline) within 24 h after birth in a 1:1 ratio. The primary outcome will be survival without BPD at 36 weeks of postmenstrual age. The secondary outcomes will include the mortality rate, BPD severity, other common preterm complication rates, respiratory support duration, length and cost of hospitalization, and long-term respiratory and neurodevelopmental outcomes during a 2-year follow-up. Furthermore, we will perform single-cell RNA sequencing for cord blood cells and blood cells 3-10 days after intervention and detect whether reactive oxygen species and inflammatory cytokines are present. Conclusion: This will be the first randomized, placebo-controlled, double-blinded trial to evaluate the efficacy of ACBMNC infusion to prevent BPD in monozygotic twin premature infants and investigate the underlying protective mechanisms. The results of this trial will provide valuable clinical evidence for translational application of cord blood cell therapy in very preterm infants.Trial registration: ClinicalTrials.gov, NCT05087498, registered 10/09/2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BAD7&selectaction=Edit&uid=U0002PLA&ts=2&cx=qvyylv.

Aberrant Expression of Thymosin Beta-4 Correlates With Advanced Disease and BRAF V600E Mutation in Thyroid Cancer.

Thymosin beta-4 (TMSB4X) was recently identified as a differentially expressed gene between malignant and non-malignant thyroid cells via single-cell RNA sequencing. In the present study, we aimed to study the immunostaining pattern of TMSB4X in benign and malignant thyroid neoplasms. Immunohistochemical analysis revealed that normal thyroid tissue or benign thyroid disorders exhibited undetectable immunoreactivity against TMSB4X except for positive staining of inflammatory infiltrates and stromal cells associated with autoimmune thyroid disease. By contrast, overexpression of TMSB4X was observed in a variety of thyroid malignancies, including papillary, follicular, poorly differentiated, and undifferentiated thyroid cancer. Among 141 patients with differentiated thyroid cancer, higher TMSB4X expression was associated with papillary tumor type, extrathyroidal extension, lymph node metastasis, and BRAF V600E mutation. The results were consistent with those from the public transcriptomic datasets. In summary, TMSB4X expression was aberrantly increased in various types of thyroid cancer, and higher TMSB4X expression was correlated with advanced disease characteristics. Thymosin beta-4 may be a novel downstream effector of the BRAF V600E mutation.

The Adsorption Potential of Cr from Water by ZnO Nanoparticles Synthesized by Azolla pinnata.

Aqueous solutions containing toxic elements (TEs) (such as hexavalent chromium (Cr (VI)) can be toxic to humans even at trace levels. Thus, removing TEs from the aqueous environment is essential for the protection of biodiversity, hydrosphere ecosystems, and humans. For plant fabrication of zinc oxide nanoparticles (PF-ZnONPs), Azolla pinnata plants were used, and X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), SEM, and FTIR techniques were used for the identification of PF-ZnONPs and ZnONPs, which were used to remove Cr (VI) from aqueous solution. A number of adsorption parameters were studied, including pH, dose, concentration of metal ions, and contact time. The removal efficiency of PF-ZnONPs for Cr (VI) has been found to be 96% at a time (60 min), 69.02% at pH 4, and 70.43% at a dose (10 mg·L-1). It was found that the pseudo-second-order model best described the adsorption of Cr (VI) onto PF-ZnONPs, indicating a fast initial adsorption via diffusion. The experimental data were also highly consistent with the Langmuir isotherm model calculations.