Intra-bone marrow mesenchymal stem cell transplantation modulates myeloid bias tendency of hematopoietic stem and progenitor cells in severe MRL/lpr lupus mice.

The hematopoietic homeostasis in the bone marrow is inextricably intertwined with the immune milieu in peripheral circulation. Researches investigating the pathogenesis of systemic lupus erythematosus (SLE) have defined considerable secretion of inflammatory mediators and activation of pro-inflammatory cells. However, the impacts of "extrinsic" factors on hematopoietic stem and progenitor cells (HSPCs) remain unclear, and it is uncertain whether treatments can help coordinate the biased differentiation. In this study, we showed differences in the proportions of common myeloid progenitors (CMP) and myeloid output in the bone marrow of premorbid and morbid MRL/lpr mice using flow cytometry. RNA-seq analysis of lineage-affiliated transcriptional factors and dysregulated genes within lin- HSPCs revealed inflammation potentiation during disease progression. Further, intra-bone marrow mesenchymal stem cells transplantation (IBM-MSCT) partially coordinated myeloid generation and counteracted lupus-associated inflammation gene alterations, compared to intravenous injection. Additionally, co-culturing with umbilical cord mesenchymal stem cells (UC-MSCs) intervened in myeloid lineage tendency, as detected by RT-qPCR of myeloid-related genes. Our research demonstrated enhanced tendency toward myeloid differentiation and highlighted the feasibility of IBM-MSCT for lineage-biased HSPCs in MRL/lpr lupus model, providing novel insight into hematopoiesis and MSC-related treatments for SLE.

c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

Investigations of the reaction mechanism of sodium with hydrogen fluoride to form sodium fluoride and the adsorption of hydrogen fluoride on sodium fluoride monomer and tetramer.

CONTEXT: The reaction between Na and HF is a typical harpooning reaction which is of great interest due to its significance in understanding the elementary chemical reaction kinetics. This work aims to investigate the detailed reaction mechanisms of sodium with hydrogen fluoride and the adsorption of HF on the resultant NaF as well as the (NaF)4 tetramer. The results suggest that the reaction between Na and HF leads to the formation of sodium fluoride salt NaF and hydrogen gas. Na interacts with HF to form a complex HF···Na, and then the approaching of F atom of HF to Na results in a transition state H···F···Na. Accompanied by the broken of H-F bond, the bond forms between F and Na atoms as NaF, then the product NaF is yielded due to the removal of H atom. The resultant NaF can further form (NaF)4 tetramer. The interaction of NaF with HF leads to the complex NaF···HF; the form I as well as II of (NaF)4 can interact with HF to produce two complexes (i.e., (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF), but the form III of (NaF)4 can interact with HF to produce only one complex (NaF)4(III)···HF. These complexes were explored in terms of noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. NCI analyses confirm the existences of attractive interactions in the complexes HF···Na, NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF. QTAIM analyses suggest that the F···Na interaction forms in the HF···Na complex while the F···H hydrogen bonds form in NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF complexes. Natural bond orbital (NBO) analyses were also applied to analyze the intermolecular donor-acceptor orbital interactions in these complexes. These results would provide valuable insight into the chemical reaction of Na and HF and the adsorption interaction between sodium fluoride salt and HF. METHODS: The calculations were carried out at the M06-L/6-311++G(2d,2p) level of theory which were performed using the Gaussian16 program. Intrinsic reaction coordinate (IRC) calculations were carried out at the same level of theory to confirm that the obtained transition state was true. The molecular surface electrostatic potential (MSEP) was employed to understand how the complex forms. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analysis was used to know the topology parameters at bond critical points (BCPs) and intermolecular interactions in the complex and intermediate. The topology parameters and the BCP plots were obtained by the Multiwfn software.

CFL1 restores the migratory capacity of bone marrow mesenchymal stem cells in primary Sjögren's syndrome by regulating CCR1 expression.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease. There is no relevant research on whether the migratory ability of bone marrow mesenchymal stem cells (BM-MSC) is impaired in patients with pSS (pSS-BMMSC). METHODS: Trajectories and velocities of BM-MSC were analyzed. Transwell migration assay and wound healing assay were used to investigate the migratory capacity of BM-MSC. The proliferative capacity of BM-MSC was evaluated by EDU and CCK8 assay. RNA-seq analysis was then performed to identify the underlying mechanism of lentivirus-mediated cofilin-1 overexpression BM-MSC (BMMSCCFL1). The therapeutic efficacy of BMMSCCFL1 was evaluated in NOD mice. RESULTS: The migratory capacity of pSS-BMMSC was significantly reduced compared to normal volunteers (HC-BMMSC). The expression of the motility-related gene CFL1 was decreased in pSS-BMMSC. Lentivirus-mediated CFL1 overexpression of pSS-BMMSC promoted the migration capacity of pSS-BMMSC. Furthermore, RNA-seq revealed that CCR1 was the downstream target gene of CFL1. To further elucidate the mechanism of CFL1 in regulating BM-MSC migration and proliferation via the CCL5/CCR1 axis, we performed a rescue experiment using BX431 (a CCR1-specific inhibitor) to inhibit CCR1. The results showed that CCR1 inhibitors suppressed the migration and proliferation capacity of MSC induced by CFL1. CONCLUSION: The pSS-BMMSC leads to impaired migration and proliferation, and overexpression of CFL1 can rescue the functional deficiency and alleviate disease symptoms in NOD mice. Mechanically, CFL1 can regulate the expression level of the downstream CCL5/CCR1 axis to enhance the migration and proliferation of BM-MSC.

Recurrent malignant solitary fibrous tumor of pelvis: A case report and treatment approach.

RATIONALE: Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that typically arise from the pleura but can also occur in various locations throughout the body. Although there are increasingly more reports of extra-pleural SFTs, reports of SFTs in bone are very rare, and a malignant SFT accompanying recurrence of pelvis has not yet been reported. PATIENT CONCERNS: We herein present the case of a 15-year-old male who experienced intermittent numbness in his right buttock, accompanied by radiating pain in his lower limbs for 6 months. Radiological examinations revealed an expansive, heterogeneous enhanced mass in the sacral and iliac regions, with a branch of the right internal iliac artery feeding the tumor. DIAGNOSES: The histological examination suggest a diagnosis of a malignant SFT with high proliferation activity. INTERVENTIONS: The sacral mass was surgically excised. OUTCOMES: Following the surgery, the patient experienced a local recurrence of the tumor at 9 months and was administered adjuvant imatinib treatment. Recent magnetic resonance imaging contrast-enhanced displayed shrinkage of the tumor, which may provide certain evidence for chemotherapy for the treatment of recurrence of malignant SFTs in the pelvic region. LESSONS: Complete surgical excision is the recommended treatment for this rare disease entity, and the role of adjuvant therapies is controversial due to their rarity. Our case underscores the challenges in managing recurrent malignant SFTs and highlights the importance of a thorough diagnostic workup. Further research is needed to establish the role of adjuvant therapies in the management of these tumors.

Extraoral type of intraductal papilloma in sublingual gland: A case report.

INTRODUCTION: It is rare for intraductal papilloma (IDP), a benign papillary tumor, to occur in the sublingual gland (SLG). CASE SUMMARY: A 55-year-old man incidentally found a painless mass in his left submandibular region (SMR). He had a history of two surgeries for bilateral SLG cyst. Contrast enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI) were performed. The patient received trans-cervical excision of left residual SLG in combination with excision of left submandibular gland (SMG). The postoperative course was uneventful and no signs of recurrence during 5 months of follow-up. DISCUSSION: For a SMR mass, extraoral type of IDP in SLG should be considered in the differential diagnosis.

Simultaneous nitrification and denitrification in a PCL-supported constructed wetland with limited aeration.

Considerable advances have been made in the substrate design and operation strategies of constructed wetlands to facilitate nitrogen elimination. However, few studies examined the complicated interaction between solid organic substrates and limited aeration on nitrogen removal. A vertical flow constructed wetlands in gradient distribution of inorganic and solid organic substrates (polycaprolactone/PCL) (P-VFCW) and a controlled vertical flow constructed wetland without PCL (C-VFCW) were developed for the tertiary treatment of municipal tailwater. Results indicated that ammonia was nearly converted to nitrate, while the total nitrogen removal efficiencies (TNREs) in C-VFCW were negligible. In P-VFCW, however, optimal TNREs approached 95% with an aeration rate of 0.06 mL·min-1 and hydraulic retention time (HRT) of 24 h, and simultaneous nitrification and denitrification process (SND) in aerobic conditions was confirmed. As for the spatial microbial community structure evolution, Comamonas, which is associated with heterotrophic nitrification and anoxic/aerobic denitrification, was enriched along the vertical profiles of P-VFCW. Autotrophic nitrifier (Nitrospira), aerobic denitrifier (Bradyrhizobium and Azospira), and anoxic denitrifier (Ignavibacterium and Methyloversatilis) were dominated in different depths of P-VFCW, respectively. Besides, Canna indica biomass in P-VFCW was significantly larger than that in C-VFCW, which was attributed to the plant adaption response to diverse nitrogen. The P-VFCW in gradient distribution of inorganic and solid carbon sources under limited aeration is a promising technology for advanced nitrogen removal.

The Effects of an mRNA Covid-19 Vaccine Booster on Immune Responses in Cancer-Bearing Veterans.

Immunocompromised cancer patients are at significant risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A method to identify those patients at highest risk is needed so that prophylactic measures may be employed. Serum antibodies to SARS-CoV-2 spike protein are important markers of protection against COVID-19 disease. We evaluated total and neutralizing antibody levels pre and post third booster vaccine and compared responses among different cancer-bearing and healthy veterans. This as a prospective, single site, comparative cohort observational trial. The setting was the West Palm Beach VA Medical Center cancer center. All veterans received a third SARS-CoV-2 mRNA booster. The main outcomes were anti-SARS-CoV-2 spike IgG and neutralizing antibodies to wild-type, and B.1.617, BA1, BA2, and BA4/5 variants were measured. Disease type and therapy, COVID-19 infection, and anti-CD20 antibody treatments were documented. The third mRNA vaccine booster increased the mean blood anti-spike IgG five-fold. The second anti-spike level was equal or greater than the first in 129/140 veterans. All the groups except the myeloma group, had post-booster antibody levels significantly higher than pre-booster with 4-fold, 12-fold, 4-fold, 6-fold and 3.5-fold increases for the control, solid tumor, CLL, B cell lymphoma and all B cell malignancy cohorts. The myeloma set showed only a non-significant 1.7-fold increase. Recently anti-CD20 antibody-treated patients were shown to have approximately 200-fold less anti-S IgG production after vaccine booster than other patients. There was a 2.5-fold enhancement of wild-type virus mean neutralizing antibodies after a third mRNA booster and mean neutralization of Delta and Omicron variants increased 2.2, 6.5, 7.7, and 6.2-fold versus pre-boost levels. B cell malignancies failed to show increased post-booster neutralization. The third SARS CoV-2 booster increased total anti-spike IgG and neutralizing antibodies for most subjects. Veterans with B cell malignancies particularly myeloma and those receiving anti-CD20 monoclonal antibodies had the weakest humoral responses. Neutralizing antibody responses to Omicron variants were less than for wild-type virus. A subset of patients without humoral immunity post-booster should be considered for prophylactic antibody or close monitoring.

Intratracheal administration of umbilical cord-derived mesenchymal stem cells attenuates hyperoxia-induced multi-organ injury via heme oxygenase-1 and JAK/STAT pathways.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is not merely a chronic lung disease, but a systemic condition with multiple organs implications predominantly associated with hyperoxia exposure. Despite advances in current management strategies, limited progress has been made in reducing the BPD-related systemic damage. Meanwhile, although the protective effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) or their exosomes on hyperoxia-induced lung injury have been explored by many researchers, the underlying mechanism has not been addressed in detail, and few studies have focused on the therapeutic effect on systemic multiple organ injury. AIM: To investigate whether hUC-MSC intratracheal administration could attenuate hyperoxia-induced lung, heart, and kidney injuries and the underlying regulatory mechanisms. METHODS: Neonatal rats were exposed to hyperoxia (80% O2), treated with hUC-MSCs intratracheal (iT) or intraperitoneal (iP) on postnatal day 7, and harvested on postnatal day 21. The tissue sections of the lung, heart, and kidney were analyzed morphometrically. Protein contents of the bronchoalveolar lavage fluid (BALF), myeloperoxidase (MPO) expression, and malondialdehyde (MDA) levels were examined. Pulmonary inflammatory cytokines were measured via enzyme-linked immunosorbent assay. A comparative transcriptomic analysis of differentially expressed genes (DEGs) in lung tissue was conducted via RNA-sequencing. Subsequently, we performed reverse transcription-quantitative polymerase chain reaction and western blot analysis to explore the expression of target mRNA and proteins related to inflammatory and oxidative responses. RESULTS: iT hUC-MSCs administration improved pulmonary alveolarization and angiogenesis (P < 0.01, P < 0.01, P < 0.001, and P < 0.05 for mean linear intercept, septal counts, vascular medial thickness index, and microvessel density respectively). Meanwhile, treatment with hUC-MSCs iT ame liorated right ventricular hypertrophy (for Fulton's index, P < 0.01), and relieved reduced nephrogenic zone width (P < 0.01) and glomerular diameter (P < 0.001) in kidneys. Among the beneficial effects, a reduction of BALF protein, MPO, and MDA was observed in hUC-MSCs groups (P < 0.01, P < 0.001, and P < 0.05 respectively). Increased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1ß, and IL-6 expression observed in the hyperoxia group were significantly attenuated by hUC-MSCs administration (P < 0.01, P < 0.001, and P < 0.05 respectively). In addition, we observed an increase in anti-inflammatory cytokine IL-10 expression in rats that received hUC-MSCs iT compared with rats reared in hyperoxia (P < 0.05). Tran scriptomic analysis showed that the DEGs in lung tissues induced by hyperoxia were enriched in pathways related to inflammatory responses, epithelial cell proliferation, and vasculature development. hUC-MSCs administration blunted these hyperoxia-induced dysregulated genes and resulted in a shift in the gene expression pattern toward the normoxia group. hUC-MSCs increased heme oxygenase-1 (HO-1), JAK2, and STAT3 expression, and their phosphorylation in the lung, heart, and kidney (P < 0.05). Remarkably, no significant difference was observed between the iT and iP administration. CONCLUSION: iT hUC-MSCs administration ameliorates hyperoxia-induced lung, heart, and kidney injuries by activating HO-1 expression and JAK/STAT signaling. The therapeutic benefits of local iT and iP administration are equivalent.

Insight into sulfur dioxide and its derivatives metabolism in living system with visualized evidences via ultra-sensitive fluorescent probe.

Sulfur dioxide (SO2) and its derivatives have long been considered as hazardous environmental pollutants but commonly used as food additives in safe dose range. They also could be produced from biological metabolism process of sulfur-containing amino acids. However, their physiological roles remain extremely obscure mainly due to lack of efficient tools for monitoring and imaging strategy establishment. Furthermore, most of current studies of this aspect focus on novel probe design or just imaging them rather than on the ins and outs. Therefore, there is a high significance of establishing highly sensitive detection strategy for monitoring SO2 derivatives in living systems, food and environment. Herein, we design a fluorescent probe MS-Bindol for sensitively detecting SO2 derivatives with a low detection limit (0.2 nM). We have established an imaging strategy for investigation of SO2 derivatives metabolism in living cells and zebrafish, providing visualize evidences and verified that SO2 derivatives could be synthetized from thiosulfate and glutathione(GSH) and be hardly consumed by using sulfite oxidase inhibitors (ferricyanide or arsenite). Moreover, the probe also exhibits excellent practicability in food as well as environmental samples. Our studies may help biologist for better understanding SO2 derivatives metabolism and deeply explore their physiological roles in biological systems.

Indole Alkaloids from a Soil-Derived Clonostachys rosea.

Clonorosins A (1) and B (2), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids (3-9), were isolated from the soil-derived fungus Clonostachys rosea YRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental. To assist in determining the absolute configuration of the chiral carbon in the side chain of 2,5-diketopiperazine derivatives, flexible analogues 3i-3iv were synthesized and analyzed. 1 was active against Fusarium oxysporum with an MIC value of 50 µg/mL. 7 and 8 showed excellent activity against human HeLa and HepG2 cells with IC50 values of 0.12-0.60 µM.

Heterotopic accessory spleen with squamous epithelial cyst in pancreas mimicking other pancreatic tumor: a case report.

A 49-year-old female undergoing a periodic health examination at other hospital revealed a mass in the tail of pancreas. The patient denied any personal history of surgery except subtotal hysterectomy because of multiple myomas in uterus 7 years ago, family history of abdominal cancer and trauma. Physical examination and laboratory finding (including tumor marker) were unremarkable. Chest X-ray result was normal. Contrast enhanced ultrasound (CEUS) examination showed a well-defined hypoechoic pancreatic mass which was suggestive of solid pseudopapillary tumor. Contrast enhanced computed tomography (CE-CT) of the abdomen revealed a mass of hypodensity suggestive of intraductal papillary mucinous neoplasm. Because of the risk of bleeding and exclusion of surgical contraindications, patient underwent laparoscopic surgery. Intraoperatively, a solid mass was identified in the tail of pancreas, the intraoperative frozen pathological examination suggested a heterotopic accessary spleen (HAS) with squamous epithelial cyst. Partial pancreatectomy was performed. The uniqueness of this case is that the spleen can be ectopic to the pancreas, what is even more unexpected is that the HAS undergone cystic change. When encountering a pancreatic mass, we need to think about the possibility of HAS. In conclusion, it is important to diagnose HAS with squamous cyst in the pancreatic tail presenting as other pancreatic masses.

Copigmentation evidence of oenin with phenolic compounds: A comparative study of spectrographic, thermodynamic and theoretical data.

The copigmentation effects of polyphenol with different structures vary greatly. Therefore, the aim of this study is to investigate possible interactions in red wine model solutions between oenin and three phenolic compounds: danshensu, caffeic acid and rosmarinic acid. Our results show that the copigmentation of rosmarinic acid is the strongest among the compounds tested. The colourimetric parameters indicate that colour intensity becomes enhanced with increasing concentration of these copigments, leading to darker and more vivid bluish colours. Thermodynamic and quantum chemical investigations are performed to interpret the absorption properties in the visible range. Fluorescence spectroscopy confirms the interaction between caffeic acid and oenin, while FTIR spectroscopic results further suggest a role for hydrogen bonds in the overall process. To our knowledge, this is the first experimentally corroborated direct evidence of hydrogen bonds in copigmentation.

A Human Umbilical Cord Mesenchymal Stem Cell-Conditioned Medium/Chitosan/Collagen/ß-Glycerophosphate Thermosensitive Hydrogel Promotes Burn Injury Healing in Mice.

We investigated the effects of a human umbilical cord mesenchymal stem cell-conditioned medium (MSC-CM)/chitosan/collagen/ß-glycerophosphate (ß-GP) thermosensitive hydrogel (MSC-CM/hydrogel) on mice with third-degree burns. MSC-CM was collected and mixed with chitosan, collagen, and ß-GP to generate the thermosensitive MSC-CM/hydrogel, which was stored in the liquid phase at 4°C. The wounds of established third-degree burned mice were then externally covered with the MSC-CM/hydrogel, which formed a gel when placed on the wounds at physiological temperature. Injured mice in three additional groups were treated with unconditioned MSC medium (UM), MSC-CM, or UM/chitosan/collagen/ß-GP thermosensitive hydrogels. Skin wound samples were obtained 4, 14, and 28 days after burning for further analysis by hematoxylin and eosin and Ki-67 staining. Wound healing rates and times, in addition to immunohistochemical results, were then compared and analyzed among the four groups. Application of the MSC-CM/hydrogel shortened healing time, limited the area of inflammation, enhanced reepithelialization, promoted the formation of high-quality, well-vascularized granulation tissue, and attenuated the formation of fibrotic and hypertrophic scar tissue. In summary, MSC-CM/hydrogel effectively promotes wound healing in third-degree burned mice.

Is ultrasound combined with computed tomography useful for distinguishing between primary thyroid lymphoma and Hashimoto's thyroiditis?

INTRODUCTION: The aim of the study is to investigate the usefulness of ultrasound combined with computed tomography (CT) for distinguishing between primary thyroid lymphoma (PTL) and Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: The investigation was conducted retrospectively in 80 patients from January 2000 to July 2018. All patients underwent pathological tests to be classified into one of two groups: PTL group and HT group. The cut-off value of CT density was determined using receiver-operating characteristic (ROC) curve analysis. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of diagnosis for thyroid by CT alone, ultrasound alone, and the combination of CT plus ultrasound were calculated. RESULTS: Of the 80 study patients, 27 patients were PTL and 53 patients were HT. Mean CT density had a sensitivity of 90.6% and a specificity of 88.9% at a cut-off value of 53.5 HU, with area under the curve (AUC) 0.88. Ultrasound combined with CT had the highest specificity, accuracy, and PPV compared with CT alone and ultrasound alone (p value < 0.05). CONCLUSIONS: Features such as extremely hypoechogenicity, enhanced posterior echo, cervical lymphadenopathy in ultrasound image, and linear high-density strand signs, and very low density in CT imaging have high sensitivity and specificity in thyroid lymphoma. Therefore, ultrasound combined with CT may be useful for distinguishing between PTL and HT.

Influence of neonatal gender on cord blood CD34+ cell amplification and gene expression.

The present study attempted to evaluate whether neonatal gender affects the hematopoietic potential of cord blood (CB) transplants and, if so, to determine the underlying molecular mechanisms. CD34+ cells from CB were isolated and divided into male and female groups. CD34+CD38- cell populations were then compared using fluorescence-assisted cell sorting (FACS) and a colony formation assay was performed. Next, a Genechip microarray analysis was used to identify differentially expressed genes (DEGs). Finally, the Genechip results were validated by FACS analysis. It was revealed that the male group had higher amplification efficiency. Gene ontology analysis indicated differences in the biological function of the DEGs between the two groups. Kyoto Encyclopedia of Genes and Genomes analysis suggested that the hematopoietic cell lineage signaling pathway was upregulated in the male group along with high expression levels of genes including interleukin (IL) 6 signal transducer (glycoprotein 130), IL-7 and IL-7 receptor. It was speculated that this may be partially due to numerous upregulated DEGs being involved in chromosomal segregation and hematopoietic cell lineage signaling pathways in CD34+ cells from the male group.

Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection.

The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naïve hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans.

Hydrogen bonding promoted simple and clean photo-induced reduction of C-X bond with isopropanol.

We herein report a simple and clean photo-induced metal-free reduction of C-X bond under an atmosphere of air at room temperature. Isopropanol is used as both the reducing reagent and solvent. Various functional groups (acids, esters, alcohols, anilines, phenols, indoles, pyridines, cyano and trifluoromethyl groups) and other heterocyclic compounds are tolerated. Different organic halides (including C-I, C-Br and C-Cl bonds) can be dehalogenated with moderate to excellent yields. Polyhalides are also reduced chemoselectively and efficiently. DFT calculation suggests a six-membered ring transition state via C-XH-O hydrogen bonding to decrease the activation energy.

Intermolecular interactions between σ- and π-holes of bromopentafluorobenzene and pyridine: computational and experimental investigations.

The characters of σ- and π-holes of bromopentafluorobenzene (C6F5Br) enable it to interact with an electron-rich atom or group like pyridine which possesses an electron lone-pair N atom and a π ring. Theoretical studies of intermolecular interactions between C6F5Br and C5H5N have been carried out at the M06-2X/aug-cc-pVDZ level without and with the counterpoise method, together with single point calculations at M06-2X/TZVP, wB97-XD/aug-cc-pVDZ and CCSD(T)/aug-cc-pVDZ levels. The σ- and π-holes of C6F5Br exhibiting positive electrostatic potentials make these sites favorably interact with the N atom and the π ring of C5H5N with negative electrostatic potentials, leading to five different dimers connected by a σ-holen bond, a σ-holeπ bond or a π-holeπ bond. Their geometrical structures, characteristics, nature and spectroscopy behaviors were systematically investigated. EDA analyses reveal that the driving forces in these dimers are different. NCI, QTAIM and NBO analyses confirm the existence of intermolecular interactions formed via σ- and π-holes of C6F5Br and the N atom and the π ring of C5H5N. The experimental IR and Raman spectra gave us important information about the formation of molecular complexes between C6F5Br and C5H5N. We expect that the results could provide valuable insights into the investigation of intermolecular interactions involving σ- and π-holes.

Helios expression in regulatory T cells promotes immunosuppression, angiogenesis and the growth of leukemia cells in pediatric acute lymphoblastic leukemia.

Regulatory T cells (Tregs) characterized by the transcription factor forkhead box P3 (FoxP3) are crucial for maintaining immune tolerance and preventing autoimmunity. However, FoxP3 does not function alone and Helios is considered a potential candidate for defining Treg subsets. In this study, we investigated the expression and function of Helios for identifying Tregs in childhood precursor B-cell acute lymphoblastic leukemia (pre-B ALL). Our results demonstrated that patients with pre-B ALL had a higher percentage of Helios+ FoxP3+ CD4+ Tregs. And there was a positive correlation between the expression of Helios and the suppressive function of Tregs, the risk gradation of ALL. Helios in combination with CD4 and FoxP3 may be an effective way to detect functional Tregs in pre-B ALL by promoting the secretion of transforming growth factor (TGF)-ß1. Furthermore, Helios+ Tregs could regulate angiogenesis in the BM niche of pre-B ALL via the VEGFA/VEGFR2 pathway. We also found Helios+ Tregs decreased apoptosis rate of nalm-6 cells by up-regulating the expression of anti-apoptosis protein Bcl-2. In summary, these data strongly imply the physiological importance of Helios expression in Tregs, and suggest that the manipulation of Helios may serve as a novel strategy for cancer immunotherapy.